Bupivacaine; meloxicam is a combination of an amide local anesthetic and nonsteroidal anti-inflammatory drug (NSAID) indicated for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle procedures, small-to-medium open abdominal procedures, or lower extremity total joint arthroplasty procedures in adults. In clinical trials, bupivacaine; meloxicam significantly reduced postoperative pain intensity and opioid use for up to 72 hours compared to bupivacaine alone or placebo. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. The safety and effectiveness of local anesthetics depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Meloxicam, like all NSAIDs, may exacerbate hypertension and congestive heart failure and may cause an increased risk of serious cardiovascular thromboembolism, acute myocardial infarction, and stroke, which can be fatal. Also, serious gastrointestinal (GI) tract adverse effects, such as GI bleeding or inflammation and stomach or other GI perforation and ulceration, can occur without warning or symptoms in patients receiving NSAIDs.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Bupivacaine is to be administered by or under the supervision of experienced clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise from bupivacaine exposure.
-Ensure oxygen, resuscitative equipment and medications, and personnel resources are immediately available for proper management of toxic reactions and related emergencies.
Route-Specific Administration
Other Administration Route(s)
Soft Tissue or Periarticular Administration
-Visually inspect the product for particulate matter and discoloration prior to administration whenever solution and container permit; the solution is a clear, pale yellow to yellow, viscous liquid.
-Avoid additional local anesthetic administration within 96 hours after bupivacaine; meloxicam administration. If additional local anesthetic administration cannot be avoided based on clinical need, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity.
-The safety of additional NSAID administration during treatment has not been evaluated. Monitor for NSAID toxicity if additional NSAID medication is indicated during the postoperative period.
-Use is compatible with surgical mesh materials, including polypropylene (Prolene), Gore-tex, and polyester, silicone membranes, bone cement, and metal alloys used in surgical implants.
-The solution does not degrade sutures. When using monofilament sutures, 3 or more knots are recommended, as contact with the solution may cause a single knot to loosen or untie.
-Storage: Vials are for single dose only. Discard any unused product.
Preparation
-Do not dilute. Do not mix with water, saline, or other local anesthetics as the product will become more viscous and difficult to administer.
-Prepare vial for filling of syringe(s) by attaching vented vial spike. Prepare syringe by filling with air, then attach to vented vial spike.
-Invert vial to allow product to fill the vial neck and push air into the vial. Withdraw dose of bupivacaine; meloxicam into provided syringe(s) immediately prior to use. Apply syringe tip cap until product delivery.
Administration
-When a topical antiseptic is applied, allow the surgical site to dry before the local anesthetic is applied.
-Remove the syringe tip cap and attach the Luer lock cone-shaped applicator to the syringe.
-Using the Luer lock cone-shaped applicator only, apply the solution to tissues within the surgical site after final irrigation and suctioning, and prior to suturing of each layer, when multiple tissue layers are involved.
--For foot and ankle procedures, apply to the proximal and distal ends (i.e., beyond the bony repair) of the wound.
-For small-to-medium open abdominal procedures, apply above and below the fascial repair.
-For lower extremity total joint arthroplasty, apply directly to the joint capsule, the anteromedial tissues and periosteum, and the anterolateral tissues and periosteum after placement of the components.
-Only apply the solution to the tissue layers below the skin incision and not directly onto the subdermal layer or the skin.
-Use only the amount of solution necessary to coat the tissues to avoid leaking from the surgical wound after closure. The solution becomes more viscous during contact with moisture in tissues, which allows the product to stay in place.
Significant CNS toxicities have been reported with all local anesthetics, including bupivacaine. These neurologic adverse effects are generally associated with high serum drug concentrations and vary based on the dose, administration route, and status of the patient. Possible early warning signs of CNS toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremor, twitching, CNS depression, or drowsiness. Central nervous system adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include dizziness (22%), fever (14%), and headache (7% to 14%).
Limit exposure of articular cartilage to bupivacaine; meloxicam due to the potential risk of chondrolysis. There have been reports of chondrolysis, mainly involving the shoulder joint, in pediatric and adult patients receiving local anesthetics via continuous intraarticular infusion administration after arthroscopic or other surgical procedures. The time to onset of symptoms (e.g., joint pain, stiffness, loss of motion) is variable but may begin as early as the second month after surgery. Some patients affected have required additional diagnostic and therapeutic procedures, arthroplasty, or shoulder replacement.
Methemoglobinemia has been reported with local anesthetic use. Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after local anesthetic exposure and are characterized by cyanotic skin discoloration and abnormal coloration of the blood. Other symptoms may include headache, rapid heart rate, shortness of breath, dizziness, and drowsiness. Serious central nervous system and cardiovascular adverse events, including seizures, coma, arrhythmias, and death may occur. Since methemoglobin concentrations may continue to rise, immediately discontinue any oxidizing agents to avoid serious central nervous system and cardiovascular adverse events, including seizures, coma, arrhythmias, and death. Depending on the severity of symptoms, patients may require supportive care, such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
NSAIDs, such as meloxicam, may cause an increased risk of serious cardiovascular thromboembolism, myocardial infarction, and stroke, which can be fatal. Estimates of increased relative risk range from 10% to 50% or more, based on the drug and dose studied. The risk may increase with increased exposure, as measured in dose or duration. Significant cardiovascular risk has been observed within days to weeks of NSAID initiation. NSAIDs may also lead to onset of new hypertension or worsening of preexisting hypertension, which may contribute to the increased incidence of cardiovascular adverse events. Monitor blood pressure after administration of bupivacaine; meloxicam. A meta-analysis of randomized, controlled trials demonstrated an approximately 2-fold increase in hospitalizations for heart failure among non-selective and COX-2 selective-treated patients compared to placebo. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of myocardial infarction, hospitalization for heart failure, and death. Also, fluid retention and edema have been observed in some patients treated with NSAIDs. Cardiovascular adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include bradycardia (8% to 9%), hypertension (19%), and hypotension (5%).
Long-term administration of NSAIDs, such as meloxicam, can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Nephrotoxicity has been noted in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, NSAIDs may cause a dose-dependent reduction in prostaglandin formation, thereby reducing renal blood flow precipitating overt renal decompensation. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
As with other NSAIDs, cases of serious, and sometimes fatal, GI bleeding, GI ulceration, or GI perforation have been reported in patients receiving meloxicam. Overall, GI ulcer, bleeding, or perforation occurs in approximately 1% of patients treated with NSAIDs for 3 to 6 months and in about 2% to 4% of patients treated for a year with trends continuing with longer durations of use. Gastrointestinal adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include dysgeusia (9%), constipation (24%), nausea (50%), and vomiting (26%).
Elevated hepatic enzymes (less than 3 times the upper limit of normal) may occur in up to 15% of patients taking NSAIDs, including meloxicam. Notable elevations of ALT or AST (3 times or more the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. Rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, hepatic necrosis, and hepatic failure have been reported with NSAIDs. The risk of these events after a single-dose local application of bupivacaine; meloxicam is uncertain. If clinical signs and symptoms consistent with hepatotoxicity develop or if systemic manifestations occur, evaluate the patient.
Meloxicam has been associated with anaphylactoid reactions. Advise patients to seek emergency help if an anaphylactic reaction occurs. NSAIDs, including meloxicam, can cause serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions. Dermatologic adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include abnormal skin odor (8%), pruritus (7%), and hyperhidrosis (5%).
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with bupivacaine; meloxicam has any signs or symptoms of anemia, monitor hemoglobin or hematocrit. Hematologic adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include anemia (5%) and leukocytosis (7%).
Local inflammatory adverse reactions reported with bupivacaine; meloxicam in clinical trials and occurring with 5% or more incidence and higher than saline placebo include incision site edema (17%), incision site erythema (13%), impaired wound healing (6%), incision site cellulitis (4%), wound dehiscence (4%), and incision site infection (3%). Muscle twitching occurred in 6% of bupivacaine; meloxicam-treated patients in clinical trials.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a multi-organ hypersensitivity reaction, has occurred with NSAIDs. Some of these events have been life-threatening or fatal. DRESS typically presents as fever, rash, and/or lymphadenopathy in conjunction with other organ system involvement including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations such as fever and lymphadenopathy may be present without evidence of a rash. If such symptoms occur, evaluate the patient immediately and treat as clinically indicated.
Bupivacaine use requires an experienced clinician who is well versed in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise from bupivacaine exposure. Bupivacaine use also requires a specialized care setting; use bupivacaine only if the following are immediately available: oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.
Bupivacaine; meloxicam is not indicated for epidural administration, intrathecal administration, intravenous administration, intraarterial administration, intra-articular administration, regional nerve blocks, or pre-incisional or pre-procedural locoregional anesthetic techniques. Unintended intravascular or intrathecal injection of bupivacaine may be associated with systemic toxicities, including central nervous system or cardiorespiratory depression and coma, ultimately progressing to respiratory arrest.
Limit exposure of articular cartilage to bupivacaine; meloxicam due to the potential risk of chondrolysis. Continuous intraarticular infusion administration of local anesthetics, including bupivacaine, after arthroscopic and other surgical procedures is an unapproved use, and there have been postmarketing reports of chondrolysis in patients receiving such infusions. Patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures, and some required arthroplasty or shoulder replacement.
Bupivacaine; meloxicam is contraindicated in patients with known amide local anesthetic hypersensitivity, salicylate hypersensitivity or NSAID hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) and in patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. A subpopulation of patients with asthma may have aspirin-sensitive asthma, which may include chronic rhinosinusitis complicated by nasal polyps, severe and potentially fatal acute bronchospasm, and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported, bupivacaine; meloxicam is contraindicated in patients with aspirin-sensitive asthma. When bupivacaine; meloxicam is used in patients with preexisting asthma without known aspirin sensitivity, monitor patients for exacerbation of asthma symptoms. Bupivacaine; meloxicam is contraindicated in patients with previous serious rash or skin reactions due to NSAIDs. The use of NSAIDs, including meloxicam, can cause serious and potentially fatal skin reactions including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Educate patients about the signs and symptoms of serious skin reactions.
Patients with impaired cardiovascular function (e.g., hypotension, AV block) are less able to compensate for functional changes associated with bupivacaine-related prolongation of AV conduction. Monitor patients closely for changes in blood pressure, heart rate, or ECG.
Bupivacaine; meloxicam is contraindicated in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of myocardial infarction and stroke was found in clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days after CABG surgery. Meloxicam, like all NSAIDs, may cause an increased risk of serious cardiovascular thromboembolism, including myocardial infarction or stroke, which can be fatal. Some observational studies found that this increased risk of serious cardiovascular (CV) thrombotic events began as early as the first weeks of treatment; the increase in CV risk has been most consistently observed at higher doses. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. The risk of these events after single-dose local application of bupivacaine; meloxicam is uncertain. Current evidence is insufficient to determine if the risk of an event is higher or lower for any particular NSAID compared to other NSAIDs. There is no consistent evidence that concomitant use of aspirin mitigates the increased risk for cardiovascular thrombotic events. Guidelines recommend against NSAID use in patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality and CV complications associated with their use. Observational data from a national registry demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning the first week of treatment. An increased relative risk of death in NSAID users continued during the follow-up period of 4 years. Data demonstrate that patients treated with NSAIDs were more likely to die in the first year after myocardial infarction compared to those not treated with NSAIDs. Caution is recommended when administering meloxicam to patients with cardiac disease, cardiomyopathy, cardiac arrhythmias (e.g., tachycardia), significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), hypertension, pre-existing kidney disease, or fluid retention. Closely monitor blood pressure during meloxicam receipt. Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or symptoms of a cardiovascular thrombotic event. Avoid bupivacaine; meloxicam use in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If bupivacaine; meloxicam is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. The use of meloxicam may blunt the CV effects of several therapeutic agents used to treat fluid retention or edema, which have been observed with NSAID use. A meta-analysis of randomized, controlled trials demonstrated an approximately 2-fold increase in hospitalizations for heart failure among non-selective and COX-2 selective-treated patients compared to placebo. NSAIDs, including meloxicam, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking NSAIDs may have impaired response to angiotensin-converting enzyme inhibitors, thiazide diuretics, or loop diuretics. A meta-analysis demonstrated that the effect of NSAIDs on blood pressure is the greatest in hypertensive individuals receiving antihypertensive medication. Normotensive patients receiving antihypertensive therapy had higher increases in blood pressure than subjects with uncontrolled hypertension or normotensive subjects receiving no hypertensive therapy.
Closely monitor patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), infants younger than 6 months, and those with concurrent exposure to oxidizing agents or their metabolites for signs and symptoms of methemoglobinemia. Methemoglobinemia is characterized by cyanotic skin discoloration and abnormal coloration of the blood, presenting immediately or within hours of local anesthetic exposure. Discontinue bupivacaine and any other oxidizing agents immediately and initiate supportive care (e.g., oxygen, hydration) if necessary to avoid serious central nervous system and cardiovascular effects. Severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
NSAIDs, including meloxicam, may increase the risk of bleeding events. Comorbid conditions, such as coagulopathy or concomitant use of anticoagulant therapy, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs), may increase this risk. Monitor these patients for signs of bleeding.
NSAIDs, including meloxicam, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and GI perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a more than 10-fold increased risk for developing a GI bleed compared to patients without risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant oral corticosteroid therapy, anticoagulants, aspirin, or selective serotonin reuptake inhibitors (SSRIs), tobacco smoking, ethanol ingestion, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease or coagulopathy are at increased risk for GI bleeding. To minimize GI risks in NSAID-treated patients, use the recommended dosage for each surgical procedure, and avoid administration of more than 1 NSAID at a time. If additional NSAID medication is indicated in the postoperative period, monitor patients for signs and symptoms of NSAID-related GI adverse reactions. In the setting of concomitant low-dose aspirin use for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Avoid NSAID use in higher risk populations unless the benefits are expected to outweigh the risks of bleeding; consider alternate therapy other than NSAIDs in higher risk patients as well as those with active GI bleeding. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. If a serious GI adverse event is suspected, promptly initiate evaluation and treatment.
Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, use bupivacaine; meloxicam cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Meloxicam has not been adequately studied in patients with severe hepatic impairment. Use bupivacaine; meloxicam in patients with severe hepatic impairment only if the benefits are expected to outweigh the risks; monitor patients for signs of worsening liver function. Consider increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic disease. No dose adjustment of bupivacaine; meloxicam is necessary in patients with mild to moderate hepatic impairment. Elevations of ALT or AST (3 times or more the upper limit of normal) have been reported in NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. The risk of these events after single-dose local application of bupivacaine; meloxicam is uncertain. Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), perform a clinical evaluation of the patient.
Correct volume status in dehydrated or hypovolemic patients before starting bupivacaine; meloxicam. Monitor renal function in patients with hepatic or renal impairment, heart failure, dehydration, or hypovolemia during bupivacaine; meloxicam use. Avoid bupivacaine; meloxicam use in patients with advanced renal disease or renal failure unless the benefits are expected to outweigh the risk of worsening renal function. If bupivacaine; meloxicam is used in patients with advanced renal disease, monitor patients for signs and symptoms of worsening renal function. Consider reducing the dose of bupivacaine; meloxicam for patients with mild to moderate renal impairment. Because bupivacaine and meloxicam and their metabolites are excreted by the kidney, the risk of toxic reactions to these drugs may be greater in patients with impaired renal function. Renal toxicity has been observed in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, NSAID use may cause a dose-dependent reduction in prostaglandin formation, and secondarily, renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
The pharmacological activity of bupivacaine; meloxicam in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infection.
In patients who are known or suspected to be CYP2C9 poor metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin or phenytoin), consider bupivacaine; meloxicam dose reduction, as these patients may have abnormally high plasma concentrations of meloxicam due to reduced metabolic clearance. Monitor these patients for adverse effects.
Bupivacaine is substantially excreted by the kidney, and the risk of bupivacaine toxicity may be greater in geriatric patients who are more likely to have impaired renal function. Because geriatric patients are more likely to have decreased renal function, take care in bupivacaine; meloxicam dose selection; it may be useful to monitor renal function. Consider reducing the dose of bupivacaine; meloxicam for elderly patients. Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions, although the applicability of this to a single administration of low-dose meloxicam in bupivacaine; meloxicam is uncertain. According to the Beers Criteria, NSAIDs are considered potentially inappropriate medications (PIMs) for use in geriatric patients. NSAIDs may cause new or worsening gastric and duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk groups including those above 75 years of age, or those taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet medications. The risk of ulcers, gross bleeding, or perforation is cumulative with continued use. Avoid the chronic use of systemic NSAIDs in high-risk geriatric patients, unless other alternatives are not effective, and the patient can take a gastroprotective agent. Avoid use in patients with a history of gastric or duodenal ulcers, unless other alternatives are not effective and the patient can take a gastroprotective agent. The use of a gastroprotective agent, like a proton pump inhibitor or misoprostol, reduces but does not eliminate, GI risks. NSAIDs can also increase blood pressure and induce kidney injury. The Beers Panel recommends avoiding NSAIDs in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: symptomatic heart failure or chronic kidney disease Stage 4 or higher (CrCl less than 30 mL/minute) (acute kidney injury, further decline of renal function). Use caution in patients with asymptomatic heart failure.
Bupivacaine is contraindicated in patients undergoing obstetrical paracervical nerve block anesthesia; the use of bupivacaine in this technique has resulted in fetal bradycardia and death. There are no adequate and well-controlled studies with bupivacaine in pregnant women. Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the pregnant woman, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. If bupivacaine is used during pregnancy, inform the patient of the potential hazard to the fetus. Placental transfer of local anesthetics is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. Fetal to maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding since only free, unbound drug is available for placental transfer. Bupivacaine is about 95% bound to plasma proteins, resulting in a low fetal to maternal ratio (0.2 to 0.4). Subcutaneous administration of bupivacaine to pregnant rabbits during organogenesis resulted in embryofetal lethality at clinically relevant doses. Decreased pup survival occurred at a dose comparable to the daily maximum recommended human dose on a body surface area basis in a rat pre- and post-natal developmental study. Avoid meloxicam use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive.
Bupivacaine is minimally excreted into breast milk. There are no human data available on whether meloxicam is present in human milk. There is no available information on the effects of bupivacaine; meloxicam on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for bupivacaine; meloxicam and any potential adverse effects on the breast-fed infant from bupivacaine; meloxicam or the underlying maternal condition.
NSAIDs, such as meloxicam, may pose a reproductive risk by delaying or preventing prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing infertility evaluation. Also, meloxicam may impair fertility in males of reproductive potential. Oral administration of meloxicam to male rats for 35 days resulted in decreased sperm count and motility and histopathological evidence of testicular degeneration at 0.3-times the maximum recommended human dose based on body surface area comparison. It is not known if these effects on fertility are reversible. The clinical relevance of these findings is unknown.
For postsurgical local analgesia after foot and ankle procedures, small-to-medium open abdominal procedures, or lower extremity total joint arthroplasty procedures:
-for postsurgical local analgesia after foot and ankle procedures, such as bunionectomy:
Soft Tissue or Periarticular dosage:
Adults: Up to 60 mg of bupivacaine and 1.8 mg of meloxicam (2.3 mL) applied to the proximal and distal ends (i.e., beyond the bony repair) of the wound.
-for postsurgical local analgesia after small-to-medium open abdominal procedures, such as open inguinal herniorrhaphy:
Soft Tissue dosage:
Adults: Up to 300 mg of bupivacaine and 9 mg of meloxicam (10.5 mL) applied above and below the fascial repair.
-for postsurgical local analgesia after lower extremity total joint arthroplasty procedures, such as total knee arthroplasty:
Soft Tissue or Periarticular dosage:
Adults: Up to 400 mg of bupivacaine and 12 mg of meloxicam (14 mL) applied directly to the joint capsule, anteromedial tissues and periosteum, and anterolateral tissues and periosteum after placement of the components.
Maximum Dosage Limits:
-Adults
400 mg bupivacaine and 12 mg meloxicam soft tissue or periarticular application per procedure.
-Geriatric
400 mg bupivacaine and 12 mg meloxicam soft tissue or periarticular application per procedure.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use bupivacaine; meloxicam in patients with severe hepatic impairment only if the benefits are expected to outweigh the risks; monitor patients for signs of worsening liver function. Consider increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic disease. No dose adjustment of bupivacaine; meloxicam is necessary in patients with mild to moderate hepatic impairment.
Patients with Renal Impairment Dosing
The use of bupivacaine; meloxicam in patients with severe renal impairment is not recommended. Consider reducing the bupivacaine; meloxicam dose in patients with mild to moderate renal impairment.
Intermittent hemodialysis
Meloxicam is not dialyzable. When using bupivacaine; meloxicam in patients on hemodialysis do not exceed maximum recommended dose or use with other meloxicam-containing products.
*non-FDA-approved indication
Abciximab: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Acebutolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Acetaminophen: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Codeine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Dextromethorphan: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Diphenhydramine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Hydrocodone: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Oxycodone: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Phenylephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of acyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Adagrasib: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with adagrasib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and adagrasib is a moderate CYP2C9 inhibitor.
Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as nonsteroidal antiinflammatory drugs may increase the risk of developing nephrotoxicity even in patients who have normal renal function. The use of adefovir with NSAIDs may be done cautiously. As stated in the current adefovir prescribing information, 'Ibuprofen (800 mg PO three times daily), when given concomitantly with adefovir dipivoxil, increased the adefovir Cmax by 33% and AUC by 23%, as well as urinary recovery. The increase appears to be due to higher oral bioavailability, not a reduction in renal clearance of adefovir.' In an in vitro investigation, the antiviral effect of adefovir was unaltered and the renal proximal tubule accumulation of adefovir was inhibited by the presence of a NSAID. Adefovir is efficiently transported by the human renal organic anion transporter 1, and the presence of this transporter appears to mediate the accumulation of the drug in renal proximal tubules. The in vitro study suggests that the use of a NSAID with adefovir may potentially reduce the nephrotoxic potential of adefovir. Of course, NSAIDs are associated with nephrotoxicity of their own; therefore, further data on the interaction between NSAIDs and adefovir in humans are needed.
Albuterol; Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Aldesleukin, IL-2: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Alendronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Alendronate; Cholecalciferol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Alfentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aliskiren: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren.
Alpha-blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Alteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Amikacin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
Amiloride: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Aminolevulinic Acid: (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable.
Aminosalicylate sodium, Aminosalicylic acid: (Major) Avoid concomitant use of meloxicam with aminosalicylic acid due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as aminosalicylic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Amiodarone: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with amiodarone is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and amiodarone is a moderate CYP2C9 inhibitor.
Amitriptyline: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Amlodipine; Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Amlodipine; Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Amphotericin B lipid complex (ABLC): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B liposomal (LAmB): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Anagrelide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Antithrombin III: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Apixaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Aprepitant, Fosaprepitant: (Moderate) Use caution if bupivacaine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in bupivacaine-related adverse effects for several days after administration of a multi-day aprepitant regimen. In vitro, bupivacaine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of bupivacaine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. (Moderate) Use caution if meloxicam and aprepitant, fosaprepitant are used concurrently, and monitor for an increase in meloxicam-related adverse effects for several days after administration of a multi-day aprepitant regimen. Meloxicam is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of meloxicam. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aprepitant is also a CYP2C9 inducer and meloxicam is a CYP2C9 substrate. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as NSAIDs, as the risk of renal impairment may be increased.
Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Articaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use articaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Asciminib: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with asciminib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and asciminib is a CYP2C9 inhibitor.
Aspirin, ASA: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Aspirin, ASA; Caffeine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Dipyridamole: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Aspirin, ASA; Omeprazole: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Atazanavir: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects. (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate.
Atazanavir; Cobicistat: (Moderate) Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of local anesthetics and an increased potential for QT prolongation or other adverse effects. (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate. (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Atenolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Atenolol; Chlorthalidone: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Azathioprine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Azelastine; Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Azilsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Bacitracin: (Major) Avoid concurrent use of bacitracin with nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Barbiturates: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Beclomethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Belladonna; Opium: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Benzalkonium Chloride; Benzocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzocaine; Butamben; Tetracaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of meloxicam with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Beta-blockers: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Betamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Betaxolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and nonsteroidal antiinflammatory drugs (NSAIDs) are used concomitantly. Coadministration of betrixaban and NSAIDs may increase the risk of bleeding.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Bismuth Subsalicylate: (Major) Avoid concomitant use of meloxicam with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Avoid concomitant use of meloxicam with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Bisoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Bivalirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Brimonidine; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Budesonide; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Bumetanide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Busulfan: (Major) Due to the thrombocytopenic effects of busulfan, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Butalbital; Acetaminophen: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of low dose aspirin or analgesic doses of aspirin and meloxicam is generally not recommended due to the increased risk of bleeding and renal impairment. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Meloxicam is not a substitute for low dose aspirin for cardiovascular protection. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Calcium-channel blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Candesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Cannabidiol: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with cannabidiol is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and cannabidiol is a weak CYP2C9 inhibitor.
Capecitabine: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with capecitabine is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and capecitabine is a weak CYP2C9 inhibitor.
Capreomycin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Captopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Carbamazepine: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Carmustine, BCNU: (Major) Due to the thrombocytopenic effects of carmustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine.
Carteolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Carvedilol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Celecoxib; Tramadol: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ceritinib: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ceritinib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ceritinib is a weak CYP2C9 inhibitor.
Chlorambucil: (Major) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chlordiazepoxide; Amitriptyline: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Chloroprocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroquine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as chloroquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chlorpheniramine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlorpheniramine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Chlorpropamide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Cholestyramine: (Minor) Pretreatment for four days with cholestyramine before IV meloxicam significantly increased the clearance of meloxicam by 50%. This interaction may occur via reduction of enterohepatic recycling of meloxicam in the gastrointestinal tract; the impact on oral dosing of meloxicam or overall clinical relevance is not established.
Choline Salicylate; Magnesium Salicylate: (Major) Avoid concomitant use of meloxicam with choline salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Major) Avoid concomitant use of meloxicam with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Cholinesterase inhibitors: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ciclesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cidofovir: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Cilostazol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ciprofloxacin: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Citalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Cladribine: (Major) Due to the thrombocytopenic effects of cladribine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Clofarabine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Clomipramine: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Clopidogrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Cobicistat: (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Phenylephrine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Colistimethate, Colistin, Polymyxin E: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Colistin: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as bupivacaine, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with bupivacaine. Treatment with bupivacaine may be initiated no sooner than 1 week after completion of conivaptan therapy.
Corticosteroids: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Cyclophosphamide: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as cyclophosphamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Cyclosporine: (Moderate) Monitor serum creatinine, potassium concentrations, and cyclosporine concentrations closely when systemic cyclosporine is given with meloxicam. Renal dysfunction associated with cyclosporine may be potentiated by concurrent usage of NSAIDs, particularly in a dehydrated patient. The effects of NSAIDs on the production of renal prostaglandins may also cause changes in the elimination of cyclosporine. Monitor patients closely for signs and symptoms of cyclosporine toxicity and infection, as NSAIDs may mask fever, pain, or swelling.
Cytarabine, ARA-C: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy.
Dabrafenib: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and meloxicam, a CYP2C9 substrate, may result in decreased levels of meloxicam; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of meloxicam efficacy. In addition, an increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Patients should be monitored closely for bleeding.
Dacarbazine, DTIC: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Dapsone: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Daratumumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Darunavir: (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Darunavir; Cobicistat: (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed. (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. (Moderate) The plasma concentrations of meloxicam may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while meloxicam is a CYP3A4 substrate. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed. (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Dasatinib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Deflazacort: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Delavirdine: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with delavirdine is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and delavirdine is a moderate CYP2C9 inhibitor. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as delavirdine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Desipramine: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia.
Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by desvenlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be monitored for signs and symptoms of bleeding while taking desvenlafaxine with NSAIDs.
Dexamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Diclofenac: (Major) Avoid concomitant use of diclofenac with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diclofenac; Misoprostol: (Major) Avoid concomitant use of diclofenac with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diflunisal: (Major) Avoid concomitant use of diflunisal with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diltiazem: (Moderate) Diltiazem may inhibit the CYP3A4-mediated metabolism of bupivacaine. Use caution when administering these drugs concomitantly.
Diphenhydramine; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Diphenhydramine; Naproxen: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Dipyridamole: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Disulfiram: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with disulfiram is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and disulfiram is a weak CYP2C9 inhibitor.
Docetaxel: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Donepezil: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Donepezil; Memantine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Dorzolamide; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Doxazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Doxepin: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Meloxicam is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Drospirenone: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Estetrol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Ethinyl Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended.
Duloxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant duloxetine and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Edoxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Efavirenz: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with efavirenz is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and efavirenz is a moderate CYP2C9 inhibitor.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with efavirenz is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and efavirenz is a moderate CYP2C9 inhibitor. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with efavirenz is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and efavirenz is a moderate CYP2C9 inhibitor.
Efgartigimod Alfa; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Elbasvir; Grazoprevir: (Moderate) Administering bupivacaine with elbasvir; grazoprevir may result in elevated bupivacaine plasma concentrations. Bupivacaine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. (Moderate) Administering meloxicam with elbasvir; grazoprevir may result in elevated meloxicam plasma concentrations. Meloxicam is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ivacaftor is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ivacaftor is a weak CYP2C9 inhibitor.
Eltrombopag: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when elvitegravir is administered with meloxicam as there is a potential for decreased meloxicam concentrations. Meloxicam is primarily metabolized by CYP2C9, while elvitegravir is a CYP2C9 inducer. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Caution is warranted when elvitegravir is administered with meloxicam as there is a potential for decreased meloxicam concentrations. Meloxicam is primarily metabolized by CYP2C9, while elvitegravir is a CYP2C9 inducer. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. (Minor) Plasma concentrations of bupivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Emtricitabine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Enalapril, Enalaprilat: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Entecavir: (Moderate) The manufacturer of entecavir recommends monitoring for adverse effects when coadministered with NSAIDs. Entecavir is primarily eliminated by the kidneys; NSAIDs can affect renal function. Concurrent administration may increase the serum concentrations of entecavir and adverse events.
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and nonsteroidal antiinflammatory drugs (NSAIDs), and monitor blood pressure. The concomitant use of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations.
Epoprostenol: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
Eprosartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Eptifibatide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with nonsteroidal antiinflammatory drugs (NSAIDs) is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases. Patients receiving concomitant NSAIDs may be at increased risk of perforation.
Escitalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Esmolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Ethacrynic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Ethanol: (Major) Advise patients to avoid alcohol and alcohol-containing products while taking NSAIDs. Concomitant ingestion of alcohol with NSAIDs increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol is a mucosal irritant and NSAIDs decrease platelet aggregation. Routine ingestion of alcohol and NSAIDs can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of NSAIDs and alcohol should be avoided. Chronic alcohol ingestion is often associated with hypoprothrombinemia and this condition increases the risk of bleeding.
Ethiodized Oil: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Etidronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Etodolac: (Major) Avoid concomitant use of etodolac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Etomidate: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Etravirine: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with etravirine is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and etravirine is a weak CYP2C9 inhibitor.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as meloxicam, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of meloxicam during coadministration with fenofibric acid.
Fenoprofen: (Major) Avoid concomitant use of fenoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Fentanyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for epidural analgesia or additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Floxuridine: (Major) Due to the thrombocytopenic effects of floxuridine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluconazole: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with fluconazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and fluconazole is a moderate CYP2C9 inhibitor. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Fludrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Flunisolide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluorouracil, 5-FU: (Major) Due to the thrombocytopenic effects of fluorouracil, 5-FU, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluoxetine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Flurbiprofen: (Major) Avoid concomitant use of flurbiprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Flutamide: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Salmeterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluticasone; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fluvastatin: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with fluvastatin is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and fluvastatin is a weak CYP2C9 inhibitor.
Fluvoxamine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluvoxamine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Formoterol; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Fosamprenavir: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Foscarnet: (Minor) The risk of renal toxicity may be increased if foscarnet is used in conjuction with other nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor renal function carefully during concurrent therapy.
Fosinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Furosemide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and meloxicam use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Galantamine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Garlic, Allium sativum: (Minor) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving drugs with a known potential risk for bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs).
Gemfibrozil: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with gemfibrozil is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and gemfibrozil is a weak CYP2C9 inhibitor.
General anesthetics: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Gentamicin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as gentamicin.
Ginger, Zingiber officinale: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and NSAIDs as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glipizide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glipizide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glyburide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Glyburide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Gold: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Grapefruit juice: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with grapefruit juice is necessary. Concurrent use may increase meloxicam exposure. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and grapefruit juice is a moderate CYP2C9 inhibitor.
Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Guanfacine: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Homatropine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects. (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Hydantoins: (Minor) Bupivacaine is metabolized by CYP3A4. Hydantoins induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Hydromorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydroxyurea: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as hydroxyurea, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of meloxicam with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibandronate: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate, respectively, and nonsteroidal antiinflammatory drugs. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as nonsteroidal antiinflammatory drugs (NSAIDs); the risk of bleeding may be increased. If coadministration with NSAIDs is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibuprofen lysine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ibuprofen; Famotidine: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ibuprofen; Oxycodone: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with meloxicam, a CYP3A substrate, as meloxicam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as ifosfamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Iloprost: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Imatinib: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Imipramine: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indapamide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Indinavir: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Indomethacin: (Major) Avoid concomitant use of indomethacin with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and nonsteroidal antiinflammatory drugs (NSAIDs) due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of NSAIDs in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Iodixanol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iohexol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iomeprol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iopamidol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Iopromide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ioversol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Ioxaglate Meglumine; Ioxaglate Sodium: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Irbesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with meloxicam may result in increased serum concentrations of meloxicam. Meloxicam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Isoflurane: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Isosorbide Mononitrate: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Isosulfan Blue: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Itraconazole: (Major) Concomitant use of itraconazole and meloxicam may result in decreased plasma concentrations of meloxicam. Caution should be used when meloxicam is used concurrently with itraconazole and its effects should be monitored; dosage adjustment of meloxicam may be required. (Moderate) Itraconazole causes a modest increase in bupivacaine serum concentrations. It is unclear if this increase is due to CYP3A4 inhibition by itraconazole or if other mechanisms are involved.
Ivacaftor: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ivacaftor is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ivacaftor is a weak CYP2C9 inhibitor.
Ketamine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Ketoconazole: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as ketoconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Ketoprofen: (Major) Avoid concomitant use of ketoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Ketorolac: (Contraindicated) Concomitant use of ketorolac with another NSAID is contraindicated. Increased adverse gastrointestinal effects are possible if ketorolac is used with other systemic nonsteroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors.
Labetalol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Leflunomide: (Moderate) In vitro studies indicate that the M1 metabolite of leflunomide inhibits cytochrome P450 2C9, the enzyme responsible for the metabolism of many NSAIDs. Leflunomide altered protein binding and thus, increased the free fraction of ibuprofen by 13% to 50%. The clinical significance of the interactions with NSAIDs is unknown. There was extensive concomitant use of NSAIDs in phase III clinical studies of leflunomide in the treatment of rheumatoid arthritis, and no clinical differential effects were observed. However, because some NSAIDs have been reported to cause hepatotoxic effects, some caution may be warranted in their use with leflunomide.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bupivacaine; monitor for potential reduction in efficacy. Bupivacaine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bupivacaine; monitor for potential reduction in efficacy. Bupivacaine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Levobunolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Levoketoconazole: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as ketoconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Levomilnacipran: (Moderate) Platelet aggregation may be impaired by SNRIs such as levomilnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking levomilnacipran and NSAIDs.
Levorphanol: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use prilocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lisinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lithium: (Moderate) Monitor serum lithium concentrations during concomitant nonsteroidal anti-inflammatory (NSAID) use; reduce the lithium dose based on serum lithium concentrations and clinical response. NSAIDs decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.
Lomustine, CCNU: (Major) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of meloxicam with ritonavir may result in elevated meloxicam plasma concentrations. Meloxicam is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Losartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lumacaftor; Ivacaftor: (Minor) Concomitant use of meloxicam and lumacaftor; ivacaftor may alter meloxicam exposure; caution and close monitoring are advised if these drugs are used together. Meloxicam is primarily metabolized by CYP2C9 and is also a substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C9. Although induction of meloxicam through the secondary CYP3A pathway may lead to minor decreases in drug efficacy, the net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism is not clear. Monitor the patient for decreased meloxicam efficacy or increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ivacaftor is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ivacaftor is a weak CYP2C9 inhibitor.
Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as nonsteroidal antiinflammatory drugs (NSAIDs). Healthcare providers are advised to discontinue NSAID therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Mafenide: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Magnesium Salicylate: (Major) Avoid concomitant use of meloxicam with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Mannitol: (Major) Avoid use of mannitol and nonsteroidal anti-inflammatory drugs (NSAIDs), if possible. If use together is necessary, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Concomitant administration of nephrotoxic drugs, such as NSAIDs, increases the risk of renal failure after administration of mannitol. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Mecamylamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Mechlorethamine, Nitrogen Mustard: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meclofenamate Sodium: (Major) Avoid concomitant use of meclofenamate sodium with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Mefenamic Acid: (Major) Avoid concomitant use of mefenamic acid with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Meperidine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Mepivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use mepivacaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Mesalamine, 5-ASA: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Methadone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Methenamine; Sodium Salicylate: (Major) Avoid concomitant use of meloxicam with sodium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Methohexital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Methotrexate: (Major) Do not administer nonsteroidal anti-inflammatory drugs (NSAIDs) before or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths from severe hematologic and gastrointestinal toxicity. Use caution when NSAIDs are administered concomitantly with lower doses of methotrexate as they have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Despite potential interactions, patients with rheumatoid arthritis (RA) are often receiving concurrent treatment with NSAIDs without apparent problems. However, these doses are lower than those used in psoriasis or malignancy; higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. NSAIDs may be continued in patients with RA receiving treatment with methotrexate, although the possibility of increased toxicity has not been fully explored.
Methoxsalen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as meloxicam could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methyldopa: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Methylprednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Methylsulfonylmethane, MSM: (Moderate) Patients taking methylsulfonylmethane, MSM have reported increased bruising or blood in the stool. These effects have not been confirmed in published medical literature or during clinical studies. Use methylsulfonylmethane, MSM with caution in patients who are taking drugs with the potential for additive bleeding, including nonsteroidal antiinflammatory drugs (NSAIDs). During an available, published clinical trials in patients with osteoarthritis, patients with bleeding disorders or using anticoagulants or platelet inhibiting drugs were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving NSAIDs should be observed for potential bleeding.
Metoclopramide: (Moderate) Coadministration of bupivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Mifepristone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Milnacipran: (Moderate) Platelet aggregation may be impaired by milnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking milnacipran and NSAIDs.
Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
Mitotane: (Moderate) Use caution if mitotane and bupivacaine are used concomitantly, and monitor for decreased efficacy of bupivacaine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and bupivacaine is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of bupivacaine. (Minor) Use caution if mitotane and meloxicam are used concomitantly, and monitor for decreased efficacy of meloxicam and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and meloxicam is a minor CYP3A4 substrate; coadministration may result in decreased plasma concentrations of meloxicam.
Mitoxantrone: (Major) Due to the thrombocytopenic effects of mitoxantrone, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Modafinil: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with modafinil is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and modafinil is a weak CYP2C9 inhibitor.
Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Monoamine oxidase inhibitors: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Morphine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nabumetone: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Nadolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Naproxen: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Naproxen; Esomeprazole: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Naproxen; Pseudoephedrine: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Nebivolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Nebivolol; Valsartan: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Nefazodone: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as nefazodone, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Nelarabine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nelfinavir: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Neomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, such as aminoglycosides.
Neostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Neostigmine; Glycopyrrolate: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of meloxicam with ritonavir may result in elevated meloxicam plasma concentrations. Meloxicam is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Nitrates: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitrofurantoin: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrofurantoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitroglycerin: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Non-Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
Nortriptyline: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as fluoxetine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olopatadine; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and nonsteroidal antiinflammatory drugs (NSAIDs) when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding.
Oritavancin: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with oritavancin is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and oritavancin is a weak CYP2C9 inhibitor. (Minor) Bupivacaine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of bupivacaine may be reduced if these drugs are administered concurrently.
Oxaprozin: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxymorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Paclitaxel: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pamidronate: (Moderate) Monitor renal function during concomitant pamidronate and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Paroxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and meloxicam, a CYP3A4 substrate, may cause an increase in systemic concentrations of meloxicam. Use caution when administering these drugs concomitantly.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as bupivacaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as bupivacaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Pentamidine: (Major) Avoid concurrent or sequential use of pentamidine with meloxicam. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
Pentobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Pentosan: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Pentostatin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Perindopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Perindopril; Amlodipine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Perphenazine; Amitriptyline: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Pertuzumab; Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Phenelzine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Phenobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Phenoxybenzamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Phentolamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Photosensitizing agents (topical): (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable.
Physostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Pindolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Pioglitazone; Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Piroxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Platelet Inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as nonsteroidal antiinflammatory drugs (NSAIDS), may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic acetaminophen.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Polymyxin B: (Major) The chronic coadministration of systemic polymyxins may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since Polymyxin B is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
Posaconazole: (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Povidone-Iodine: (Moderate) Bupivacaine liposomal should not come into contact with topical antiseptics (e.g., povidone-iodine). If a topical antiseptic is applied to the surgical site, allow the site to dry completely before administering bupivacaine liposomal.
Pralatrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant administration of drugs that undergo substantial renal clearance, such as nonsteroidal antiinflammatory drugs (NSAIDs), may result in delayed clearance of pralatrexate.
Prasugrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Prazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Prednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Prednisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Prilocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use prilocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use prilocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primaquine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as primaquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primidone: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Probenecid: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Probenecid; Colchicine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Procarbazine: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
Propofol: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Propranolol: (Major) Propranolol has been shown to significantly decrease the clearance of the amide local anesthetics (e.g., lidocaine, bupivacaine, and mepivacaine). Lidocaine and bupivacaine toxicity have been reported after coadministration with propranolol. The mechanism of the interaction between propranolol and lidocaine is thought to be due to propranolol-induced decreased hepatic blood flow causing decreased elimination of lidocaine. Local anesthetics may also cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents or rapid-onset vasodilators, such as nitrates. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Protriptyline: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Pyridostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Quinapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Quinine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Quinolones: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ramipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Rasburicase: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Regorafenib: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with regorafenib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and regorafenib is a weak CYP2C9 inhibitor.
Remifentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Reteplase, r-PA: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Risedronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Ritonavir: (Moderate) Concurrent administration of meloxicam with ritonavir may result in elevated meloxicam plasma concentrations. Meloxicam is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Rivaroxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Rivastigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Ropivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use other formulations of bupivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rucaparib: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with rucaparib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and rucaparib is a weak CYP2C9 inhibitor.
Sacubitril; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Salsalate: (Major) Avoid concomitant use of meloxicam with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Secobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Selective serotonin reuptake inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Sertraline: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Sevoflurane: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
Sodium Polystyrene Sulfonate: (Major) Meloxicam oral suspension contains sorbitol and use of sorbitol with sodium polystyrene sulfonate has been implicated in cases of upper gastrointestinal injury and colonic necrosis, both potentenially fatal complications. Concomitant use of the oral solution of meloxicam and sodium polystyrene sulfonate is not recommended. Patients with renal insufficiency may be at increased risk while on such therapy. This risk of interaction does not apply to other forms of meloxicam.
Sotalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Sparsentan: (Moderate) Monitor for worsening renal function during concomitant use of sparsentan and nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX-2) inhibitors. Concomitant use increases the risk for nephrotoxicity, especially in patients with additional risk factors such as hypovolemia and chronic renal impairment.
Spironolactone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Streptomycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as streptomycin.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sufentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Sulfadiazine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with sulfamethoxazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Sulfasalazine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfonamides: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfonylureas: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
Sulindac: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Sumatriptan; Naproxen: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Tacrolimus: (Moderate) Monitor patients for signs of worsening renal function during coadministration of tacrolimus and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as nonsteroidal antiinflammatory drugs (NSAIDS) may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Telmisartan; Amlodipine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Temozolomide: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tenecteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Teniposide: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Terazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Tetracaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use tetracaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tezacaftor; Ivacaftor: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ivacaftor is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ivacaftor is a weak CYP2C9 inhibitor.
Thiazide diuretics: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Thioguanine, 6-TG: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Thrombolytic Agents: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Ticagrelor: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ticlopidine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses. (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Tipranavir: (Minor) Bupivacaine is metabolized by cytochrome P450 (CYP) 3A4 isoenzymes. Known inhibitors of CYP 3A4, such as anti-retroviral protease inhibitors, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Although not studied, dosage adjustments of bupivacaine may be needed.
Tirofiban: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of NSAIDs with tobacco smoking may enhance the risk of gastrointestinal side effects, including peptic ulcer and GI bleeding. Patients using tobacco and NSAIDs concurrently should be monitored closely for GI adverse reactions.
Tobramycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as tobramycin.
Tolmetin: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers.
Toremifene: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with toremifene is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and toremifene is a weak CYP2C9 inhibitor.
Torsemide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Tramadol; Acetaminophen: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Trandolapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Verapamil may inhibit the CYP3A4-mediated metabolism of and bupivacaine. Use caution when administering these drugs concomitantly.
Tranylcypromine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with medications that impair platelet function and to promptly report any bleeding events to the practitioner.
Treprostinil: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.
Triamcinolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
Triamterene: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Tricyclic antidepressants: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Trimipramine: (Major) Coadminister bupivacaine and tricyclic antidepressants together with caution. If epinephrine is added to bupivacaine, severe and prolonged hypertension may occur in a patient taking a TCA. Tricyclic antidepressants can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient.
Urea: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
Valacyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of valacyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Valganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as valproic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with valproic acid is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and valproic acid is a moderate CYP2C9 inhibitor.
Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Vancomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor patients for signs and symptoms of bleeding when coadministering venlafaxine with NSAIDs.
Verapamil: (Moderate) Verapamil may inhibit the CYP3A4-mediated metabolism of and bupivacaine. Use caution when administering these drugs concomitantly.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with nonsteroidal anti-inflammatory drugs is necessary due to the risk of decreased verteporfin efficacy. Oxaprozin may additionally worsen photosensitivity. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation like nonsteroidal anti-inflammatory drugs could decrease the efficacy of verteporfin therapy.
Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as meloxicam, may occur during concurrent use of vigabatrin.
Vilazodone: (Moderate) Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with NSAIDs and to promptly report any bleeding events to the practitioner.
Voclosporin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Vorapaxar: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Voriconazole: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with voriconazole is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and voriconazole is a moderate CYP2C9 inhibitor. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as voriconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
Warfarin: (Moderate) Monitor patients for signs or symptoms of bleeding during concurrent use of warfarin and nonsteroidal antiinflammatory drugs (NSAIDs). To minimize the potential for GI bleeding, use the lowest effective NSAID dose for the shortest possible duration. If signs or symptoms of bleeding occur, promptly evaluate and treat. Systemic hematological effects may also occur with the use of topical NSAIDs. NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients.
Zafirlukast: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with zafirlukast is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and zafirlukast is a weak CYP2C9 inhibitor.
Zoledronic Acid: (Moderate) Monitor renal function during concomitant zoledronic acid and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity.
Like all local anesthetics, bupivacaine causes a reversible nerve-conduction blockade by decreasing nerve membrane permeability to sodium. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. Clinically, loss of nerve function occurs in the order of 1) pain, 2) temperature, 3) touch, 4) proprioception, and 5) skeletal muscle tone. Meloxicam inhibits prostaglandin synthesis, primarily by competitive inhibition of both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, resulting in analgesic and antiinflammatory pharmacologic effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Prostaglandins are mediators of inflammation. Meloxicam may decrease prostaglandins in peripheral tissues.
Bupivacaine; meloxicam is administered by instillation to the surgical site. The rate of absorption of bupivacaine or meloxicam from bupivacaine; meloxicam is dependent upon the total dose of drug administered and the vascularity of the administration site. After bupivacaine and meloxicam have been released from the extended-release solution and are absorbed systemically, their distribution and excretion are expected to be the same as for other bupivacaine solution formulations or meloxicam oral formulations. Systemic plasma concentrations of bupivacaine and meloxicam after application of bupivacaine; meloxicam do not correlate with local efficacy. Bupivacaine is distributed to some extent to all tissues, with a high concentration in well-perfused organs such as the liver, lung, heart, and brain. Bupivacaine is highly protein-bound (95% in adults), particularly to alpha1-acid glycoprotein. Bupivacaine is metabolized primarily in the liver via conjugation with glucuronic acid. Additionally, bupivacaine is N-dealkylated by the CYP3A subfamily, CYP2C19, and CYP2D6 to form pipecolylxylidine, the major metabolite of bupivacaine. Pipecolylxylidine is hydroxylated to form glucuronide conjugates. Approximately 6% of the dose is excreted in the urine unchanged; urinary excretion is affected by urinary perfusion and pH. The mean apparent terminal half-life for bupivacaine from the extended-release solution is approximately 14 to 15 hours. Meloxicam is about 99.4% bound to human plasma proteins, primarily to albumin, and is about 99% bound in patients with renal disease. The free fraction in synovial fluid is 2.5 times higher than in plasma due to the lower albumin content in synovial fluid as compared to plasma; the significance of this penetration is unknown. Meloxicam is extensively hepatically metabolized to 4 pharmacologically inactive metabolites. The major metabolites are formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety. Specifically, 5'-carboxy meloxicam (60% of dose), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethyl meloxicam, which is itself excreted (9% of dose). In vitro studies indicate that CYP2C9 enzymes are primarily involved in this metabolic pathway, with a minor contribution by CYP3A4 enzymes. Peroxidase activity is probably responsible for the other 2 metabolites which account for 16% and 4% of the administered dose, respectively. Meloxicam excretion is predominantly in the form of metabolites, with 43% of the dose excreted in the urine and remainder appearing in the feces. Only traces of unchanged drug are excreted in the urine (0.2%) and feces (1.6%). About 6% and 13% of the dose is found in urine in the form of the 5'-hydroxymethyl and 5'-carboxy metabolites, respectively. The mean apparent terminal half-life for meloxicam from the extended-release solution is approximately 22 to 25 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP2C19, CYP2D6, CYP3A4Formation of pipecolylxylidine, the primary metabolite of bupivacaine, appears to be primarily mediated by CYP3A4. The isoenzymes CYP2C19 and CYP2D6 may play minor roles in degradation. Pipecolylxylidine constitutes 5% of the dose, and thus N-dealkylation does not appear to account for a large percentage of the drug's metabolism. Drug interactions related to CYP3A4 inhibition are unlikely. In vitro studies indicate that CYP2C9 enzymes are primarily involved in the major metabolic pathway of meloxicam, with a minor contribution by CYP3A4 enzymes.
-Route-Specific Pharmacokinetics
Other Route(s)
Soft Tissue or Periarticular Instillation Route
The rate of systemic absorption of bupivacaine or meloxicam from the instillation site is dependent upon the total dose of drug administered and the vascularity of the site. After a single 60 mg dose in patients who underwent bunionectomy (n = 17), pharmacokinetic parameters for bupivacaine were Cmax (SD) = 54 (33) ng/mL, Tmax (range) = 3 (1.6, 24) hours, AUC (0 to 120 hours post-dose) (SD) = 1,681 (1,154) hours x ng/mL, and half-life (SD) = 15 (8) hours. After a single 300 mg dose in patients who underwent herniorrhaphy (n = 16), pharmacokinetic parameters for bupivacaine were Cmax = 271 (147) ng/mL, Tmax = 18 (3, 30) hours, AUC (0 to 120 hours post-dose) = 15,174 (8,545) hours x ng/mL, and half-life = 16 (9) hours. After a single 400 mg dose in patients who underwent total knee arthroplasty (n = 53), pharmacokinetic parameters for bupivacaine were Cmax = 695 (411) ng/mL, Tmax = 21 (4, 59) hours, AUC (0 to 144 hours post-dose) = 35,890 (28,400) hours x ng/mL, and half-life = 17 (7) hours. After a single 1.8 mg dose in patients who underwent bunionectomy (n = 17), pharmacokinetic parameters for meloxicam were Cmax (SD) = 26 (14) ng/mL, Tmax (range) = 18 (8, 60) hours, AUC (0 to 120 hours post-dose) (SD) = 1,621 (927) hours x ng/mL, and half-life (SD) = 33 (36) hours. After a single 9 mg dose in patients who underwent herniorrhaphy (n = 16), pharmacokinetic parameters for meloxicam were Cmax = 225 (96) ng/mL, Tmax = 54 (24, 96) hours, and AUC (0 to 120 hours post-dose) = 18,721 (7,923) hours x ng/mL. After a single 12 mg dose in patients who underwent total knee arthroplasty (n = 53), pharmacokinetic parameters for meloxicam were Cmax = 275 (134) ng/mL, Tmax = 36 (12, 72) hours, AUC (0 to 144 hours post-dose) = 19,525 (12,259) hours x ng/mL, and half-life = 42 (37) hours. When administered at the same dose, respectively, the pharmacokinetics of bupivacaine; meloxicam are not expected to be significantly different when used in procedures with similar surgical site characteristics, tissue type, surgical area size, and vascularity.
-Special Populations
Hepatic Impairment
After bupivacaine and meloxicam have been released from the extended-release solution and are absorbed systemically, the effects of hepatic impairment are expected to be the same as for other bupivacaine and meloxicam formulations. Hepatic disease may decrease the ability of the liver to metabolize bupivacaine. Patients with severe hepatic disease may be more susceptible to developing toxic bupivacaine plasma concentrations. Hepatic impairment may alter the disposition of meloxicam. The clinical significance of this effect is not known. In subjects with mild (Child-Pugh Class I) and moderate (Child-Pugh Class II) hepatic impairment, there are no marked differences in meloxicam plasma concentrations compared to healthy volunteers. Protein binding of meloxicam is not affected by hepatic insufficiency. Patients with severe hepatic impairment (Child-Pugh Class III) have not been adequately studied.
Renal Impairment
After bupivacaine and meloxicam have been released from the extended-release solution and are absorbed systemically, the effects of renal impairment are expected to be the same as for other bupivacaine and meloxicam formulations. Bupivacaine is renally excreted. Urinary excretion is affected by urinary perfusion and factors affecting pH. Renal impairment may alter the disposition of meloxicam. The clinical significance of this effect is not known. In patients with renal insufficiency, total meloxicam plasma concentrations decreased according to the degree of renal impairment, while the free AUC values are similar. Meloxicam total clearance is likely greater in renally impaired patients due to an increase in the unbound fraction of meloxicam. Patients with severe renal insufficiency have not been adequately studied. The unbound peak meloxicam plasma concentrations are higher in patients with end-stage renal failure receiving chronic hemodialysis (1% unbound fraction) in comparison to healthy volunteers (0.3% unbound fraction). Hemodialysis does not significantly remove meloxicam from the circulation.
Geriatric
Age does not have a clinically meaningful effect on the pharmacokinetics of bupivacaine and meloxicam in the extended-release solution.
Gender Differences
Sex does not have a clinically meaningful effect on the pharmacokinetics of bupivacaine and meloxicam in the extended-release solution.
Ethnic Differences
Race and ethnicity do not have a clinically meaningful effect on the pharmacokinetics of bupivacaine and meloxicam in the extended-release solution.
Other
CYP2C9 Poor Metabolizers
Limited data show that meloxicam AUC was substantially higher in individuals with reduced CYP2C9 activity, particularly in poor metabolizers (e.g., *3/*3), compared to normal metabolizers (*1/*1).
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