Bupivacaine; epinephrine is a parenteral combination of an amide local anesthetic and vasoconstrictor indicated for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. Not all blocks are indicated for use with bupivacaine; epinephrine given clinically significant risks associated with use. Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including central nervous system or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. There have been reports of cardiac arrest with difficult resuscitation or death during use of bupivacaine for epidural anesthesia in obstetrical patients. In most cases, this has followed use of bupivacaine 0.75%. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably after unintentional intravascular injection. Bupivacaine's onset of action is moderately rapid, and its duration is significantly longer than other commonly used local anesthetics. Also, analgesia persists longer than anesthesia, which postpones the need for postoperative opioids. While most local anesthetics have a similar therapeutic index in regards to central nervous system toxicity, bupivacaine appears to be more cardiotoxic than other amide-type anesthetics. Epinephrine is added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Bupivacaine; epinephrine 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
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration, whenever the solution and container permit.
-Do not mix bupivacaine with other local anesthetics as there is insufficient data on the clinical use of such mixtures.
-Avoid rapid administration of a large volume; administer in incremental doses when feasible.
-Carefully monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness after each local anesthetic injection.
-Storage: Discard any unused portion from a single-dose vial.
Other Injectable Administration
Epidural or Intracaudal Administration
-Do not use solutions containing preservatives for caudal or epidural anesthesia.
-Administer a test dose initially and monitor the effects before the full dose is given. Repeat doses should be preceded by a test dose if not clinically contraindicated. When using a "continuous" catheter technique, give the test dose before the initial and all supplemental doses.
-Some experts question the use of bupivacaine in the test dose in children due to the potential for toxicity with unintentional intravascular administration.
-Administer slowly in incremental doses with sufficient time between doses to detect toxicity. Perform frequent aspirations before and during the injection to avoid intravascular or intrathecal injection; negative aspiration does not guarantee intravascular or intrathecal injection has been avoided.
Local Infiltration Administration
-Administer slowly in incremental doses. Perform frequent aspirations before and during the injection to avoid intravascular injection; negative aspiration does not guarantee intravascular injection has been avoided.
Nerve Block Administration
-During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access.
-Administer slowly in incremental doses. Perform frequent aspirations before and during the injection to avoid intravascular injection; negative aspiration does not guarantee intravascular injection has been avoided.
Adverse effects of bupivacaine are most often related to excessive plasma concentrations due to overdosage, rapid absorption from the injection site, unintentional intravascular injection, or slow metabolic degradation. Factors influencing plasma protein binding (e.g., age [i.e., neonates], acidosis, systemic disease, or competitive drugs) may also put patients at risk for toxicity. In general, central nervous system toxicity occurs at lower doses and lower plasma concentrations in comparison to cardiac toxicity.
Cases of respiratory arrest have been reported after administration of bupivacaine in the head or neck areas (i.e., retrobulbar, dental, stellate ganglion blocks). Patients receiving epidural doses of bupivacaine have experienced respiratory paralysis and apnea. Factors that may contribute to hypoventilation include preanesthetic medications, intraoperative analgesics or sedatives, and surgical manipulation. Closely monitor cardiovascular and respiratory vital signs when administering bupivacaine.
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. Often, the initial presentation includes symptoms of CNS stimulation such as anxiety, restlessness, incoherent speech, lightheadedness, numbness or tingling of the mouth and lips, tinnitus, dysgeusia (metallic taste), dizziness, blurred vision, and tremor or twitching. In some cases, CNS excitement may not occur or be transient, with CNS depression being the first manifestation of an adverse reaction. Depressive effects may quickly proceed to drowsiness and unconsciousness, while stimulatory effects may progress into convulsions or seizures. The incidence of seizures is dependent upon the route of administration and drug dose, with approximately 0.1% of epidural anesthetic administrations resulting in seizures. Seizures have occurred after inadvertent intravascular administration of large bupivacaine doses, as well as small doses administered into the head and neck area (i.e., retrobulbar, dental, stellate ganglion block). Other reported adverse events include anesthesia, paresthesias, weakness, muscle paralysis, nausea, vomiting, chills, and miosis.
At therapeutic concentrations, local anesthetics have minimal effect on cardiac conduction, excitability, refractoriness, or contractility. However, at toxic serum concentrations, these drugs can depress cardiac conduction, excitability, and contractility, resulting in bradycardia, hypotension, AV block, palpitations, ventricular arrhythmia exacerbation (e.g., ventricular tachycardia, ventricular fibrillation), or cardiovascular collapse leading to cardiac arrest. High bupivacaine plasma concentrations have occurred with unintended intravascular administration, repeated dosing, decreased hepatic function, diminished plasma protein binding due to acidosis, pathologically lowered plasma protein binding, or competition with other drugs for protein binding sites. Health care providers are advised to use extreme caution when administering bupivacaine 0.75% as use of this concentration has been associated with cases of cardiac arrest in obstetrical patients receiving epidural anesthesia and after inadvertent intravascular injection of the drug. The resuscitation efforts have been difficult or impossible in these circumstances despite apparent adequate preparations and appropriate management. The cardiac arrest has occurred after convulsions resulting from systemic toxicity of bupivacaine. Therefore, bupivacaine 0.75% is only recommended for use during surgeries where a high degree of muscle relaxation and long duration of drug effect are desired; it is not recommended for obstetrical anesthesia. In addition to blockade of sodium, potassium, and calcium channels within the heart, CNS-mediated effects of bupivacaine may be responsible for some adverse cardiac effects, specifically hypotension resulting from a loss of sympathetic tone after epidural administration. Treat cardiovascular side effects resulting from bupivacaine administration with general supportive physiologic measures, such as oxygen therapy, assisted ventilation, and IV fluids.
Allergic reactions to bupivacaine or other formulation ingredients are characterized by urticaria, angioedema (including laryngeal edema), pruritus, erythema, sneezing, dizziness, syncope, sinus tachycardia, hyperhidrosis, fever, nausea, vomiting, and anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity to the local anesthetic or the methylparaben used as a preservative in some formulations.
An injection site reaction, including edema or puffiness, may occur after administration of bupivacaine; epinephrine.
Adverse effects associated with spinal anesthesia or during caudal or lumbar epidural block with unintentional penetration of the subarachnoid space depend upon the amount of bupivacaine; epinephrine given subdurally. Spinal block of varying magnitude may occur and can be associated with hypotension; a high spinal is characterized by leg paralysis, loss of consciousness or coma, respiratory paralysis, and bradycardia. Other neurologic effects observed after epidural anesthesia include hypotension, headache, back pain, septic meningitis, meningismus, arachnoiditis, shivering, cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid, fecal incontinence, urinary incontinence or urinary retention, loss of perineal sensation, and sexual function. Persistent motor, sensory, and/or autonomic (sphincter control) deficit of lower spinal segments with slow (several months) or incomplete recovery has been reported rarely.
During labor and obstetric delivery, local anesthetics can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Monitor fetal heart rate continuously because fetal bradycardia has occurred in patients during bupivacaine anesthesia and may be associated with fetal acidosis. Avoid use of bupivacaine as a paracervical block anesthetic, as this technique has resulted in fetal bradycardia and fetal death. Maternal hypotension can result from regional anesthesia; patient position can alleviate this problem. Administer the injection with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, caudal, or pudendal bupivacaine anesthesia may cause decreased uterine contractility or maternal expulsion efforts and alter the forces of parturition. Bupivacaine 0.75% has been associated with inadvertent intravascular injections resulting in maternal cardiac arrest and death.
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.
Drugs used to administer anesthesia have been associated with malignant hyperthermia. Although it is unknown whether amide-type local anesthetics, such as bupivacaine, trigger this reaction, it is recommended that a standard protocol for management be available when bupivacaine is administered. Early unexplained symptoms such as tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful management includes prompt discontinuation of suspected triggering agents and institution of treatment, including oxygen, supportive measures, and dantrolene.
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. Since methemoglobin concentrations may continue to rise, immediately discontinue bupivacaine 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.
Bupivacaine; epinephrine 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; epinephrine use also requires a specialized care setting; use bupivacaine; epinephrine 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.
Avoid intravenous administration, intraarterial administration, or intrathecal administration of bupivacaine; epinephrine. Bupivacaine; epinephrine is contraindicated for use as intravenous regional anesthesia (Bier Block) due to reports of cardiac arrest and death. Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including central nervous system or cardiorespiratory depression and coma, ultimately progressing to respiratory arrest. Aspirate for blood or cerebrospinal fluid (when applicable) before injecting bupivacaine; epinephrine, both before the initial injection and with all subsequent doses, to avoid inadvertent intravascular or intrathecal administration. The absence of blood or cerebrospinal fluid does not ensure against intravascular or intrathecal injection. Administer an initial test dose before epidural administration. Monitor the patient for central nervous system and cardiovascular toxicity, as well as signs of inadvertent intravascular administration (e.g., increased heart rate, transient rise in systolic blood pressure) or intrathecal administration (e.g., decreased sensation of the buttocks, paresis of the legs, absent knee jerk) for an appropriate amount of time before the full dose is given. When using a continuous catheter technique, give test doses initially and before any reinforcing doses.
Small doses of bupivacaine; epinephrine used for local head and neck anesthesia (e.g., retrobulbar and dental blocks) may produce systemic toxicity similar to that seen with unintentional intravascular injections of larger doses. These reactions may be due to intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation or, during retrobulbar blocks, puncture of the optic nerve dural sheath with subsequent drug diffusion into the subdural space. Monitor circulation and respiration constantly; resuscitative medications and equipment and appropriate supportive personnel should be immediately available.
The presence of akinesia rather than anesthesia alone should determine the readiness of the patient for ocular surgery. Constantly monitor respiration and circulation after an ophthalmic block; there have been reports of respiratory arrest after local anesthetic injection for retrobulbar block. Resuscitative medications and equipment and appropriate supportive personnel should be immediately available. Bupivacaine 0.75% is indicated for retrobulbar block but should not be used for any other peripheral block or local infiltration, including the conjunctiva.
Give bupivacaine; epinephrine in reduced doses in patients with impaired cardiovascular function (e.g., hypotension, AV block); these patients are less able to compensate for functional changes associated with bupivacaine; epinephrine-related prolongation of AV conduction. Monitor patients closely for changes in blood pressure, heart rate, or ECG. Use bupivacaine; epinephrine with caution and in restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply such as digits, nose, external ear, or penis. Patients with arteriosclerosis, cerebrovascular disease, or hypertension and/or hypertension-related vascular disease, may exhibit exaggerated vasoconstrictor response.
Do not use bupivacaine; epinephrine solutions containing preservatives (i.e., multidose vials) for caudal, epidural, or spinal anesthesia. Spinal anesthesia is contraindicated in patients with severe bleeding, severe hypotension, shock, cardiac arrhythmias, infection at the injection site, and sepsis. Use spinal anesthesia with great caution in patients with heart block, preexisting central nervous system disorders (e.g., poliomyelitis, pernicious anemia, syphilis, or tumors), hematologic disorders predisposing to coagulopathy or patients on anticoagulant therapy, chronic backache, preoperative headache, hypotension, hypertension, arthritis, spinal deformity, technical problems (e.g., persistent paresthesias, persistent bloody tap), extremes of age, and psychosis or other causes of poor cooperation by the patient.
Bupivacaine; epinephrine is contraindicated in patients with bupivacaine or other amide local anesthetic hypersensitivity or hypersensitivity to other formulation ingredients. Do not use multidose vials in patients with paraben hypersensitivity as they contain methylparaben as a preservative. Bupivacaine; epinephrine contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite hypersensitivity is seen more frequently in persons with asthma. The overall prevalence of sulfite hypersensitivity in the general population is unknown and probably low.
Consider reduced dosing and increased monitoring for systemic toxicity in patients with moderate to severe hepatic disease who are treated with bupivacaine; epinephrine, especially with repeat doses. Amide local anesthetics such as bupivacaine are hepatically metabolized.
Bupivacaine is substantially excreted by the kidney, and risk of toxicity may be greater in patients with renal impairment or renal failure.
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.
Many drugs used during anesthesia are considered triggering agents for familial malignant hyperthermia. Although it is unknown whether amide-type local anesthetics trigger this reaction, a standard protocol for management should be available when bupivacaine; epinephrine is administered. Early unexplained tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspected trigger(s), and prompt institution of treatment (e.g., oxygen, supportive measures, dantrolene).
Use bupivacaine; epinephrine with caution in patients with diabetes mellitus or thyrotoxicosis.
Neonates and infants may be at increased risk for bupivacaine toxicity due to decreased protein binding, increased volume of distribution, decreased metabolism, and prolonged half-life. Because of these pharmacokinetic differences, systemic toxicity can be more unpredictable, with cardiac toxicity presenting concomitantly with (instead of preceding) central nervous system toxicity. Continuous infusions of bupivacaine in children have resulted in high systemic drug concentrations, cardiovascular abnormalities, and seizures. Use epidural infusions with caution in infants and children; limiting infusions to less than 48 hours may minimize the risk of toxicity. Reduce the local anesthetic infusion rate in pediatric patients at risk for seizures (e.g., preexisting seizure disorder, electrolyte imbalance); such patients are at increased risk of seizures with lower drug plasma concentrations.
Geriatric patients may require lower doses of bupivacaine; epinephrine. Patients 65 years and older, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with bupivacaine; epinephrine. In clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients. Bupivacaine is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, take care in dose selection, and it may be useful to monitor renal function.
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.
Bupivacaine; epinephrine is contraindicated in patients undergoing obstetrical paracervical nerve block anesthesia; the use of bupivacaine in this technique has resulted in fetal bradycardia and death. Unintended fetal intracranial injection of local anesthetics after intended paracervical or pudendal nerve block for obstetrical anesthesia may cause neonatal depression and seizures. Supportive measures and forced urinary excretion of the local anesthetic have been used successfully to manage this complication. Only bupivacaine 0.25% and 0.5% are indicated for obstetrical anesthesia. Bupivacaine 0.75% is not recommended for obstetrical anesthesia. Experience with nonobstetric surgical procedures in pregnant patients is not sufficient to recommend use of bupivacaine 0.75% in these patients. Cardiac arrest with difficult resuscitation or death has occurred during use of bupivacaine for epidural anesthesia; in most cases, this has followed use of bupivacaine 0.75%. Resuscitation has been difficult or impossible despite adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably after unintentional intravascular injection. Reserve bupivacaine 0.75% for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary. 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. There are no available data on the use of bupivacaine; epinephrine in human pregnancy to inform a drug-associated risk of adverse developmental outcomes. If bupivacaine; epinephrine is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to a pregnant patient. To do this, maintain the patient in the left lateral decubitus position, or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. During treatment of systemic toxicity, maternal hypotension, or fetal bradycardia after regional block, maintain the pregnant patient in the left lateral decubitus position if possible, or manually displace the uterus off the great vessels. Elevating the patient's legs will also help prevent decreases in blood pressure. Monitor the fetal heart rate continuously, and electronic fetal monitoring is highly advisable. Epidural, spinal, or pudendal nerve block may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia may prolong the second stage of labor by removing the reflex urge to bear down or interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance. The use of some local anesthetic drug products during labor and obstetric delivery may be followed by diminished muscle strength and tone in a neonate for the first day or 2 of life; however, this has not been reported with bupivacaine. 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.
Bupivacaine is minimally excreted into breast milk. Bupivacaine can persist in plasma for up to 168 hours. There is no available information on the effects of bupivacaine; epinephrine on milk production. Use bupivacaine; epinephrine in a breast-feeding woman only if clearly indicated. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for bupivacaine and any potential adverse effects on the breast-fed infant from bupivacaine or the underlying maternal condition. Due to poor oral absorption of local anesthetics, the potential for adverse effects in the nursing infant is low. In general, use of parenteral bupivacaine during surgery or other procedures allows breast-feeding of the healthy term infant to be permissible as soon as the mother is awake and alert. In a study of 27 pregnant women undergoing cesarean delivery, administration of epidural anesthesia with 0.5% bupivacaine and 2% lidocaine during delivery had no effect on the infants who were breast-fed. In a comparison study of epidural anesthesia with bupivacaine to a general anesthesia regimen, the time to first breast-feeding was significantly shorter (107 vs. 228 minutes) with bupivacaine than with general anesthesia. A prospective cohort study comparing women who received no analgesia (n = 63) to women who received continuous epidural fentanyl and either bupivacaine 0.05% to 0.1% (n = 39) or ropivacaine (n = 13) during labor and delivery found no differences between the groups in breast-feeding effectiveness or infant neurobehavioral status at 8 to 12 hours postpartum. Although bupivacaine has not been evaluated by the American Academy of Pediatrics (AAP), previous AAP recommendations considered lidocaine to be usually compatible with breast-feeding.
General dosing information:
-The dosage of bupivacaine; epinephrine administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. Administer the smallest dosage and concentration required to produce the desired result.
For local anesthesia, including infiltration anesthesia:
Infiltration Dosage (bupivacaine 0.25% and epinephrine 1:200,000):
Adults: Up to 90 mL (up to bupivacaine 225 mg) by infiltration. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: Up to 90 mL (up to bupivacaine 225 mg) by infiltration. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
For regional anesthesia, including caudal anesthesia, epidural anesthesia, or obstetric anesthesia:
-for caudal block:
Intracaudal dosage (bupivacaine 0.25% or 0.5% and epinephrine 1:200,000):
Adults: 2 to 3 mL (bupivacaine 10 to 15 mg) intracaudally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 25 mg) increments intracaudally up to 15 to 30 mL (bupivacaine 37.5 to 150 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: 2 to 3 mL (bupivacaine 10 to 15 mg) intracaudally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 25 mg) increments intracaudally up to 15 to 30 mL (bupivacaine 37.5 to 150 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
-for lumbar epidural block excluding obstetrical anesthesia:
Epidural dosage (bupivacaine 0.25%, 0.5%, or 0.75% and epinephrine 1:200,000):
Adults: 2 to 3 mL (bupivacaine 10 to 15 mg) epidurally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 37.5 mg) increments epidurally up to 10 to 20 mL (bupivacaine 25 to 150 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: 2 to 3 mL (bupivacaine 10 to 15 mg) epidurally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 37.5 mg) increments epidurally up to 10 to 20 mL (bupivacaine 25 to 150 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
-for lumbar epidural block in obstetrical anesthesia:
Epidural dosage (bupivacaine 0.25% or 0.5% and epinephrine 1:200,000):
Adults: 2 to 3 mL (bupivacaine 10 to 15 mg) epidurally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 25 mg) increments epidurally up to 10 to 20 mL (bupivacaine 25 to 100 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: 2 to 3 mL (bupivacaine 10 to 15 mg) epidurally as test dose, then 3 to 5 mL (bupivacaine 7.5 to 25 mg) increments epidurally up to 10 to 20 mL (bupivacaine 25 to 100 mg). May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
For nerve block anesthesia, including peripheral nerve block:
Perineural Dosage (bupivacaine 0.25% or 0.5% and epinephrine 1:200,000):
Adults: 5 to 90 mL (bupivacaine 12.5 to 225 mg) perineurally. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: 5 to 90 mL (bupivacaine 12.5 to 225 mg) perineurally. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
For dental anesthesia, including local infiltration and mandibular nerve block and maxillary nerve block:
Infiltration or Perineural Dosage (bupivacaine 0.5% and epinephrine 1:200,000):
Adults: 1.8 mL (bupivacaine 9 mg) by infiltration or block injection per injection site; may repeat a second dose of 1.8 mL after allowing 2 to 10 minutes for block onset if needed to produce adequate anesthesia. Do not exceed bupivacaine 90 mg for a single dental sitting.
Children and Adolescents 12 to 17 years: 1.8 mL (bupivacaine 9 mg) by infiltration or block injection per injection site; may repeat a second dose of 1.8 mL after allowing 2 to 10 minutes for block onset if needed to produce adequate anesthesia. Do not exceed bupivacaine 90 mg for a single dental sitting.
For ophthalmic anesthesia, including retrobulbar nerve block:
Retrobulbar dosage (bupivacaine 0.75% and epinephrine 1:200,000):
Adults: 2 to 4 mL (15 to 30 mg) by retrobulbar injection. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Children and Adolescents 12 to 17 years: 2 to 4 mL (15 to 30 mg) by retrobulbar injection. May repeat dose every 3 hours as needed. Do not exceed bupivacaine 400 mg/day.
Maximum Dosage Limits:
NOTE: The maximum dosage limit within the recommended dosage range must be individualized in each case after evaluating the size and physical status of the patient, as well as the anticipated rate of systemic absorption from a particular injection site.
-Adults
Bupivacaine 90 mg/dental sitting by infiltration or nerve block; bupivacaine 400 mg/day by infiltration, epidurally, or perineurally for other indications.
-Geriatric
Bupivacaine 90 mg/dental sitting by infiltration or nerve block; bupivacaine 400 mg/day by infiltration, epidurally, or perineurally for other indications.
-Adolescents
Bupivacaine 90 mg/dental sitting by infiltration or nerve block; bupivacaine 400 mg/day by infiltration, epidurally, or perineurally for other indications.
-Children
12 years: Bupivacaine 90 mg/dental sitting by infiltration or nerve block; bupivacaine 400 mg/day by infiltration, epidurally, or perineurally for other indications.
1 to 11 years: 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
Consider reduced dosing and increased monitoring for bupivacaine toxicity in patients with moderate to severe hepatic impairment.
Patients with Renal Impairment Dosing
The risk of bupivacaine toxicity may be greater in patients with renal impairment.
*non-FDA-approved indication
Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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: (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: (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) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (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: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (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. (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
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: (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: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (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.
Aclidinium; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Acrivastine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Albuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
Albuterol; Budesonide: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Alogliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alogliptin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alpha-blockers: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ambrisentan: (Major) Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking ambrisentan with a sympathomimetic.
Amiloride: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Aminosalicylate sodium, Aminosalicylic acid: (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) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Amitriptyline: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Atorvastatin: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Benazepril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Celecoxib: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Amobarbital: (Major) Amobarbital increases cardiac irritability via myocardial sensitization to catecholamines and can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Amphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Amphetamines: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Angiotensin II receptor antagonists: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Angiotensin-converting enzyme inhibitors: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
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.
Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
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.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Aspirin, ASA; Carisoprodol; 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.
Aspirin, ASA; 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.
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.
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. (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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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 and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Atomoxetine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
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.
Azelastine; Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Azilsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Azilsartan; Chlorthalidone: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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 potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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.
Benzphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Beta-blockers: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Betamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
Bexagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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 and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bromocriptine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Brompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Budesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Budesonide; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Bumetanide: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
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. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (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.
Butyrophenone: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Caffeine; Sodium Benzoate: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Calcium-channel blockers: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Canagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Canagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Candesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Captopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Carbamazepine: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Carbidopa; Levodopa; Entacapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine.
Cardiac glycosides: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Cetirizine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlordiazepoxide; Amitriptyline: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Chlorothiazide: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Codeine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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; Dextromethorphan: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Hydrocodone: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. (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) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
Chlorpromazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Chlorthalidone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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.
Ciclesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Class IA Antiarrhythmics: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Class IB Antiarrhythmics: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Clevidipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Clomipramine: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Clonidine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Clozapine: (Moderate) Clozapine may induce significant alpha-adrenergic blockade during clozapine overdose, leading to profound hypotension. Epinephrine should generally not be used to treat clozapine-induced hypotension due to the unopposed beta-activity, which potentially could worsen the hypotension.
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.
Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
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: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. (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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. (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.
COMT inhibitors: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine.
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 potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Cortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Dapagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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: (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: (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: (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.
Deflazacort: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Delavirdine: (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.
Desflurane: (Moderate) Monitor patients who are concomitantly receiving epinephrine and desflurane for the development of arrhythmias. Halogenated anesthetics, such as desflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration.
Desipramine: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Desloratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Desmopressin: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
Dexamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Dexbrompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dexmethylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dextromethorphan; Quinidine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Diazoxide: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dichlorphenamide: (Moderate) Use dichlorphenamide and epinephrine together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the long-term use epinephrine. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diethylpropion: (Major) Diethylpropion has vasopressor effects. Coadministration with other vasopressors may have the potential for serious cardiac adverse effects such as hypertensive crisis and cardiac arrhythmias.
Digoxin: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Diltiazem: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Diltiazem may inhibit the CYP3A4-mediated metabolism of bupivacaine. Use caution when administering these drugs concomitantly.
Dinoprostone, Prostaglandin E2: (Major) Oxytocics have inherent vasopressor properties; hypertensive episodes have been reported in laboring women during induction with oxytoxin. Because epinephrine is a vasopressor, concomitant use may result in severe, prolonged hypertension. In addition, epinephrine, secondary to beta2-receptor agonism, can interfere with the oxytocic action of drugs such as dinoprostone or oxytocin.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Diphenhydramine; Ibuprofen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Diphenhydramine; Naproxen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
Disopyramide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Dobutamine: (Moderate) Dobutamine may potentiate the pressor effects of epinephrine.
Dofetilide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
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.
Dopamine: (Moderate) Monitor blood pressure during concomitant use of dopamine and other vasopressors, such as epinephrine, due to the risk for severe hypertension.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Doxapram: (Moderate) Doxapram may potentiate the pressor effects of epinephrine.
Doxazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Doxepin: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dronedarone: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Droperidol: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Dulaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (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: (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.
Empagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Linagliptin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Enalapril, Enalaprilat: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Entacapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine.
Eplerenone: (Moderate) Antihypertensives, including eplerenone, antagonize the vasopressor effects of parenteral epinephrine.
Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Eprosartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Ertugliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Ethacrynic Acid: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Ethiodized Oil: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ethotoin: (Minor) Bupivacaine is metabolized by CYP3A4. Hydantoins induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Etomidate: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (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.
Exenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Felodipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Fenoldopam: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
Fexofenadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Fluconazole: (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 potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Flunisolide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluoxetine: (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.
Fluphenazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
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 potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluticasone; Salmeterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluvoxamine: (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.
Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Formoterol; Mometasone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Fosinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Fosphenytoin: (Minor) Bupivacaine is metabolized by CYP3A4. Hydantoins induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Furosemide: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
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.
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.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glipizide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glipizide; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glyburide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glyburide; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Caffeine should be avoided or used cautiously with epinephrine. CNS stimulants and sympathomimetics are associated with adverse effects such as nervousness, irritability, insomnia, and cardiac arrhythmias.
Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Guanfacine: (Moderate) Antihypertensives, including guanfacine, antagonize the vasopressor effects of parenteral epinephrine.
Haloperidol: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
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.
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: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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: (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 potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Ibuprofen; 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.
Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Ibutilide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
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: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
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) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Incretin Mimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Indapamide: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
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.
Insulin Aspart: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Degludec: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Detemir: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Glargine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Glulisine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Lispro: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin, Inhaled: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulins: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Iodixanol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iohexol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iomeprol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ionic Contrast Media: (Major) The intravascular injection of a contrast medium should never be made after the administration of vasopressors since they strongly potentiate neurologic effects. Serious neurologic sequelae, including permanent paralysis, have been reported after cerebral arteriography, selective spinal arteriography, and arteriography of vessels supplying the spinal cord.
Iopamidol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iopromide: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ioversol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ipratropium; Albuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
Irbesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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.
Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. (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. (Moderate) Monitor patients who are concomitantly receiving epinephrine and isoflurane for the development of arrhythmias. Halogenated anesthetics, such as isoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
Isophane Insulin (NPH): (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Isoproterenol: (Major) Do not administer isoproterenol and epinephrine simultaneously due to additive cardiac stimulation, which may induce serious arrhythmias. These drugs may be administered alternately provided a proper interval has elapsed between doses.
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. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
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. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Isosulfan Blue: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Isradipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Itraconazole: (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.
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. (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
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.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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.
Levalbuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
Levamlodipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Levobunolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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: (Major) Due to the effects of levomilnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine.
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.
Levothyroxine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
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. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Linagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Linagliptin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Linezolid: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
Liothyronine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Lisdexamfetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Lisinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Loop diuretics: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Lopinavir; Ritonavir: (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.
Loratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Losartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Loxapine: (Major) Patients taking loxapine can have reduced pressor response to ephedrine, phenylephrine, metaraminol, or norepinephrine, but these drugs are preferred over epinephrine if a vasopressor agent is required. The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of loxapine. This reaction can result in an apparently paradoxical condition called 'epinephrine reversal.' Epinephrine reversal can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Macitentan; Tadalafil: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
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.
Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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.
Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Metformin; Repaglinide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Metformin; Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Metformin; Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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.
Methamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
Methohexital: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Methyldopa: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Methylergonovine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Methylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Methylprednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Metolazone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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 and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Mexiletine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Milnacipran: (Major) Concomitant use of milnacipran with drugs that increase blood pressure and heart rate has not been systematically evaluated and such combinations should be used with caution. Due to the effects of milnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine. Monitor heart rate and blood pressure, and the patients clinical response to therapy if co-use is necessary. Milnacipran is associated with a mean increase in heart rate of 7 to 8 beats per minute, and higher increases in heart rate (13 beats per minute or more) occur more commonly in patients treated with milnacipran than in those receiving placebo. The mean increase from baseline was 5 to 6 mmHg in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and cases of hypertension with milnacipran have been reported, some requiring immediate treatment.
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.
Minoxidil: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. (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.
Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Naproxen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Nateglinide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nebivolol; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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.
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.
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.
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.
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.
Nicardipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Nicotine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and nicotine use. Concomitant use may potentiate sympathetic effects.
NIFEdipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Nimodipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Nirmatrelvir; Ritonavir: (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.
Nisoldipine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
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. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
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. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Nitroprusside: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Non-Ionic Contrast Media: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Nortriptyline: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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: (Moderate) Olanzapine may induce significant alpha-adrenergic blockade in overdose, leading to profound hypotension. Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity since the beta-stimulation may worsen hypotension in the setting of olanzapine overdose.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce significant alpha-adrenergic blockade in overdose, leading to profound hypotension. Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity since the beta-stimulation may worsen hypotension in the setting of olanzapine overdose. (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.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce significant alpha-adrenergic blockade in overdose, leading to profound hypotension. Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity since the beta-stimulation may worsen hypotension in the setting of olanzapine overdose.
Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Olopatadine; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Opicapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine.
Oritavancin: (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.
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.
Oxytocin: (Moderate) Oxytocin may potentiate the pressor effects of epinephrine. Severe hypertension has been reported when oxytocin was given 3 to 4 hours after prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.
Ozanimod: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Paliperidone: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of paliperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The use of other agents for vascular support is recommended when needed.
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.
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.
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.
Pentobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Perindopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Perindopril; Amlodipine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Perphenazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Perphenazine; Amitriptyline: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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. (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
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.
Phendimetrazine: (Major) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.
Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. (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.
Phenothiazines: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Phenoxybenzamine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Phentermine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
Phentermine; Topiramate: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
Phentolamine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Phenytoin: (Minor) Bupivacaine is metabolized by CYP3A4. Hydantoins induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
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.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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-sparing diuretics: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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.
Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Prazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Prednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Prednisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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.
Procainamide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (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.
Prochlorperazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Promethazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Promethazine; Phenylephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Propofol: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Protriptyline: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Pseudoephedrine; Triprolidine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
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.
Quinapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Quinidine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine.
Ramipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
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.
Regular Insulin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
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.
Repaglinide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Risperidone: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Ritonavir: (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.
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.
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.
Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sacubitril; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Safinamide: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis.
Salmeterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Secobarbital: (Minor) Bupivacaine is metabolized by CYP3A4. Barbiturates induce these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Selegiline: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Semaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
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. (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
SGLT2 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and vasopressors. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
Sotagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sotalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Spironolactone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor blood pressure during concomitant use of epinephrine and St. John's Wort. Patients receiving St. John's Wort may experience severe, prolonged hypertension when given epinephrine. St. John's Wort has been shown to weakly inhibit monoamine oxidase and may potentiate the pressor effects of epinephrine.
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.
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) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Telmisartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Telmisartan; Amlodipine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Terazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
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.
Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity. (Moderate) Theophylline may potentiate the hypokalemic effects of epinephrine.
Thiazide diuretics: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Thiazolidinediones: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Thioridazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Thiothixene: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Thyroid hormones: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
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 hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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.
Tirzepatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tolcapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine.
Torsemide: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
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) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Trandolapril; Verapamil: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Verapamil may inhibit the CYP3A4-mediated metabolism of and bupivacaine. Use caution when administering these drugs concomitantly.
Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. (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.
Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Triamcinolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Triamterene: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Tricyclic antidepressants: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Trifluoperazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Trimipramine: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine. (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.
Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
Verapamil: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Verapamil may inhibit the CYP3A4-mediated metabolism of and bupivacaine. Use caution when administering these drugs concomitantly.
Voriconazole: (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.
Ziprasidone: (Major) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of ziprasidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with alpha-1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension.
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. Complete sensory block occurs at recommended doses, but the effect on motor function varies with concentration. Specifically, when used for epidural, caudal, or peripheral nerve block, the 0.25% concentration produces incomplete motor block, the 0.5% concentration produces motor blockade with moderate muscle relaxation, and the 0.75% concentration produces complete muscle relaxation.
Systemic absorption of local anesthetics can produce cardiovascular and central nervous system (CNS) effects. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to AV block, ventricular arrhythmia, cardiac arrest, and death. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Systemic absorption of local anesthetics can produce CNS stimulation, depression, or both. CNS stimulation typically manifests as restlessness, tremors, and shivering progressing to seizures and followed by CNS depression, coma, and, ultimately, respiratory arrest. However, local anesthetics have a primary depressant effect on the medulla and higher centers; CNS depression may occur without the initial excitatory stage.
Epinephrine is a vasoconstrictor added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
Bupivacaine; epinephrine is administered parenterally. 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 bupivacaine dose is excreted in the urine unchanged; urinary excretion is affected by urinary perfusion and pH. Bupivacaine clearance is 7 to 9 mL/kg/minute, and bupivacaine elimination half-life is 1.2 to 2.9 hours in adults. Epinephrine slows bupivacaine absorption into the general circulation and thus prolongs maintenance of an active tissue concentration and prolongs the duration of anesthetic effect.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C19, CYP2D6
Formation 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.
-Route-Specific Pharmacokinetics
Other Route(s)
Absorption depends on the dose, concentration, route of administration, tissue vascularity, and degree of vasodilation surrounding the area of injection. A dilute concentration of epinephrine (1:200,000) usually reduces the rate of absorption and peak plasma concentration of bupivacaine, permitting the use of moderately larger total doses and sometimes prolonging the duration of action.
Epidural and Regional Routes
After caudal, epidural, or peripheral nerve block, bupivacaine peak blood concentrations are achieved in 30 to 45 minutes and decline to insignificant concentrations during the next 3 to 6 hours.
Infiltration Route
Bupivacaine's onset of action after dental injections is rapid (2 to 10 minutes) and may last up to 7 hours. The duration of local anesthesia after bupivacaine administration is significantly longer lasting than other commonly used local anesthetics. Analgesia persists beyond the return of sensation. Bupivacaine duration of action of ranges from 180 to 600 minutes.
-Special Populations
Hepatic Impairment
Hepatic disease may decrease the ability of the liver to metabolize bupivacaine. Patients with severe hepatic disease may be more susceptible to developing toxic plasma concentrations.
Renal Impairment
Bupivacaine is renally excreted. Urinary excretion is affected by urinary perfusion and factors affecting pH.
Pediatrics
Children
Bupivacaine Vd and half-life values decrease in children compared to infants, presumably due to an increased serum protein binding that occurs with aging. These values appear to decrease with increasing age, and therefore, children have a larger Vd and longer half-life compared to adults. In a pharmacokinetic study of 6 children (age 7.25 +/- 0.75 years), bupivacaine 2.5 mg/kg as a single bolus dose via caudal injection achieved a Cmax of 1.25 mcg/mL within 30 minutes. Mean Vd, AUC, half-life, and clearance were 2.7 L/kg, 260 mcg x minute/mL, 9.6 hours, and 10 mL/kg/minute, respectively.
Geriatric
Geriatric patients exhibited higher peak plasma concentrations and decreased plasma clearance of bupivacaine compared to younger patients after administration of parenteral bupivacaine.