Delafloxacin is a fluoroquinolone antibiotic approved in adults for oral or intravenous use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired pneumonia (CAP) due to susceptible bacteria. Disabling and potentially irreversible serious adverse reactions associated with quinolones include tendinitis, tendon rupture, peripheral neuropathy, central nervous system effects, and aortic aneurysm or dissection.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Delafloxacin tablets can be taken with or without food; however, administer at least 2 hours before or 6 hours after any antacid, multivitamin, or other medication that contains divalent or trivalent cations.
-If patients miss a dose, they should take it as soon as possible up to 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next dose, wait until the next scheduled dose.
Injectable Administration
Intravenous Administration
Reconstitution
-Reconstitute the delafloxacin 300 mg vial using 10.5 mL of 5% Dextrose for Injection or 0.9% Sodium Chloride for Injection to a concentration of 300 mg/12 mL (25 mg/mL).
-Shake vigorously until the contents of the vial are completely dissolved.
-The reconstituted vial must be further diluted.
-Storage: Reconstituted vials may be kept refrigerated at 2 to 8 degrees C (36 to 46 degrees F) or at room temperature of 20 to 25 degrees C (68 to 77 degrees F) for up to 24 hours. Do not freeze.
Dilution
-Withdraw the appropriate volume of reconstituted solution per dose, 12 mL for a 300 mg dose and 8 mL for a 200 mg dose.
-Dilute the reconstituted solution to a total volume of 250 mL using either 5% Dextrose for Injection or 0.9% Sodium Chloride for Injection to achieve a concentration of 1.2 mg/mL.
-Storage: Diluted solutions may be kept refrigerated at 2 to 8 degrees C (36 to 46 degrees F) or at room temperature of 20 to 25 degrees C (68 to 77 degrees F) for up to 24 hours. Do not freeze.
Intermittent IV infusion
-Infuse over 60 minutes.
-Do not administer with any solution containing multivalent cations through the same IV line.
-Do not co-infuse with other medications. Flush lines with 5% Dextrose for Injection or 0.9% Sodium Chloride for Injection before and after each delafloxacin infusion if administered via a common IV line.
Quinolones cause arthropathy and osteochondrosis in juvenile animals of several species. Evidence supporting sustained injury to developing joints in humans is lacking at this time; however, the possibility of rare occurrences has not been excluded. One retrospective study compared the rate of tendon or joint disorders in more than 7,000 children younger than 19 years old who received ciprofloxacin, ofloxacin, or levofloxacin with more than 20,000 children who received azithromycin. The incidence of potential tendon or joint disorders was found to be approximately 2% in both the quinolone and azithromycin groups, and verified disorders were reported in less than 1% in both groups. The authors state that this incidence is likely to reflect the background incidence of these disorders in children. Another published report evaluated the safety data collected from 2,523 children and adolescents who participated in 1 of 3 efficacy trials and were randomized to receive levofloxacin or nonquinolone antibiotics. Two of the trials were open-label and 1 was evaluator-blinded only. In addition, a subset of these children participated in a 1-year surveillance trial (n = 2,233). The safety analysis focused on 4 musculoskeletal disorders: arthralgia, arthritis, tendinopathy, and gait abnormality. The authors reported an odds ratio and 95% confidence interval of 2.2 (0.95 to 5.2) at 1 month and 1.9 (1.1 to 3.5) at 1 year after receiving levofloxacin for experiencing at least 1 of the 4 musculoskeletal disorders as reported by the patient or parent or evaluated by an investigator.
General and administration site adverse events reported in less than 2% of delafloxacin-treated patients during clinical trials include infusion-related reactions.
Hypersensitivity reactions to delafloxacin have been reported in clinical trials. Serious and sometimes fatal anaphylactoid reactions (anaphylactic shock) have been reported in patients receiving quinolones. Some reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, angioedema (pharyngeal and facial edema), dyspnea, urticaria, and itching. Immune and skin and soft tissue reactions reported in less than 2% of delafloxacin-treated patients include hypersensitivity, rash (unspecified), pruritus, urticaria, and dermatitis. Discontinue delafloxacin at the first sign of rash or other hypersensitivity.
Systemic quinolones, such as delafloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that include central nervous system effects (neurotoxicity) and psychiatric adverse events. Quinolones may cause convulsions (seizures), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremor. Psychiatric adverse events associated with quinolones include toxic psychosis, hallucinations, paranoia, depression, self-injurious behavior such as suicidal ideation or acts, confusion, delirium, disorientation, disturbances in attention, anxiety, agitation, nervousness, restlessness, insomnia, nightmares, and memory impairment. Headache has been reported in 3% of delafloxacin-treated patients during clinical trials. CNS or psychiatric adverse events reported in less than 2% of delafloxacin-treated patients during clinical trials include dizziness, dysgeusia, presyncope, syncope, agitation, anxiety, confusion, insomnia, and abnormal dreams. Neurological or psychiatric reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Discontinue delafloxacin immediately if a patient reports any central nervous system side effects or psychiatric adverse reactions.
Systemic quinolones, such as delafloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that include peripheral neuropathy. Systemic quinolones have been associated with cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons. This has resulted in reports of paresthesias (less than 2%), hypoesthesia (less than 2%), dysesthesia, and weakness. Symptoms of quinolone-induced neuropathy include pain, burning, tingling, numbness, and/or weakness, or other alterations of sensation such as light touch, temperature, position sense, and vibratory sensation and/or motor strength. These reactions can occur soon after initiation of therapy. Immediately discontinue use in patients experiencing symptoms of peripheral neuropathy. Myalgia has been reported in less than 2% of delafloxacin-treated patients during clinical trials. Serious postmarketing reports of myasthenia gravis exacerbations, including deaths and the requirement for ventilatory support, have been associated with quinolone use.
Systemic quinolones, such as delafloxacin, have been associated with disabling and potentially irreversible serious adverse reactions such as tendinopathy, including tendinitis and tendon rupture requiring surgical repair or resulting in prolonged disability. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Discontinue quinolones at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Ruptures have occurred unilaterally and bilaterally, and have mainly involved the Achilles tendon; however, ruptures in the shoulder joint, hand, biceps, thumb, and other tendon sites have been reported. The risk of tendon rupture is further increased in those over age 60, those receiving concomitant steroid therapy, and in kidney, heart, and lung transplant recipients. Other reasons for tendon ruptures include physical activity or exercise, kidney failure, and prior tendon problems.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis (less than 2%) has been reported with delafloxacin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other infectious processes that have been reported in less than 2% of delafloxacin-treated patients include fungal infection, oral candidiasis, and vulvovaginal candidiasis.
Gastrointestinal adverse events reported in delafloxacin-treated patients during clinical trials include nausea (8%), diarrhea (5% to 8%), vomiting (2%), abdominal pain (less than 2%), and dyspepsia (less than 2%).
Cardiac and vascular adverse events reported in less than 2% of delafloxacin-treated patients during clinical trials include sinus tachycardia, palpitations, bradycardia, ventricular extrasystoles, flushing, hypotension, and hypertension. Additionally, systemic quinolones are associated with an increased risk of aortic aneurysm and aortic dissection. Epidemiologic studies report an increased rate of aortic dissection within 2 months after quinolone use, particularly in elderly patients. Discontinue systemic quinolone treatment immediately if a patient reports side effects suggestive of aortic aneurysm or dissection.
Adverse events related to the special senses that were reported in less than 2% of delafloxacin-treated patients during clinical trials include tinnitus, vertigo, vestibular disorder, and blurred vision.
Blood glucose disturbances, including hyperglycemia and hypoglycemia, were reported in less than 2% of delafloxacin-treated patients during clinical trials. Because hypoglycemia, sometimes resulting in coma, occurs more frequently in elderly patients or patients with diabetes mellitus who are receiving an oral hypoglycemic agent or insulin concomitantly with delafloxacin, carefully monitor blood glucose concentrations in these patients. Discontinue delafloxacin if a hypoglycemic reaction occurs and institute appropriate therapy immediately.
Elevated hepatic enzymes, including increased ALT and AST, were reported in 3% to 5% of delafloxacin-treated patients during clinical trials. Other laboratory adverse events reported in less than 2% of delafloxacin-treated patients during clinical trials include increased blood alkaline phosphatase and increased blood creatine phosphokinase.
Renal adverse events reported in less than 2% of delafloxacin-treated patients during clinical trials include renal impairment, renal failure (unspecified), and increased serum creatinine.
Blood and lymphatic system disorders reported in less than 2% of delafloxacin-treated patients during clinical trials include agranulocytosis, anemia, leukopenia, neutropenia, and pancytopenia.
Delafloxacin is contraindicated in patients with known quinolone hypersensitivity. Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have occurred even after the first dose of the drug. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Discontinue delafloxacin immediately at the first appearance of a skin rash or any other sign of hypersensitivity.
Systemic quinolones have been associated with disabling and potentially irreversible serious adverse reactions such as tendinopathy, including tendinitis and tendon rupture requiring surgical repair or resulting in prolonged disability. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Discontinue quinolones at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Avoid quinolone use in patients with a history of tendon disorders or tendon rupture. Tendon rupture typically involves the Achilles tendon; however, ruptures of the hand, shoulder, biceps, thumb, and other tendons have also been reported. Tendinitis and tendon rupture can occur bilaterally. Rupture can occur during therapy or up to a few months after therapy has been stopped. The risk of tendon rupture is increased in older adults over 60 years of age, those receiving concomitant corticosteroid therapy, and in organ transplant recipients (including kidney, heart, and lung transplants). Other reasons for tendon ruptures include physical activity or exercise, kidney failure, or tendon problems in the past. If patients experience tendon inflammation or pain, they should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been confidently excluded.
Systemic quinolones have been associated with disabling and potentially irreversible serious neurotoxicity, including central nervous system effects, peripheral neuropathy, or psychiatric event. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Avoid quinolone use in patients who have previously experienced peripheral neuropathy. Additionally, use quinolones with caution in patients with a known or suspected CNS disorder (e.g., severe cerebrovascular disease or arteriosclerosis, seizure disorder) or in the presence of other risk factors (e.g., certain drug therapy, renal dysfunction) that may predispose to seizures or lower seizure threshold. Discontinue quinolone therapy at the first signs or symptoms of neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness, or other alterations of sensation such as light touch, pain, temperature, position sense, and vibratory sensation, and/or motor strength), central nervous system adverse events (seizures or convulsions, increased intracranial pressure (including pseudotumor cerebri), dizziness, or tremors), or psychiatric adverse events (toxic psychosis, hallucinations, paranoia, depression, suicidal thoughts or acts, confusion, delirium, disorientation, disturbances in attention, anxiety, agitation, nervousness, insomnia, nightmares, or memory impairment).
Avoid use of systemic quinolones, such as delafloxacin, in patients with a history of myasthenia gravis. Systemic quinolones may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles. Serious postmarketing events, including deaths and the requirement for ventilatory support, have been associated with quinolone use in patients with myasthenia gravis.
Use delafloxacin with caution in patients with renal disease. Some modification of dosage is recommended in patients with renal impairment. Delafloxacin is not recommended for use in patients with renal failure or end-stage renal disease (ESRD), including those receiving dialysis. In patients with severe renal impairment or ESRD (eGFR less than 15 mL/minute/1.73 m2), accumulation of the intravenous vehicle, sulfobutylether-beta-cyclodextrin (SBECD) occurs. Monitor serum creatinine closely in patients with severe renal impairment receiving intravenous delafloxacin, and consider switching to oral therapy. Discontinue delafloxacin if eGFR decreases to less than 15 mL/minute/1.73 m2.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including delafloxacin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Reserve systemic quinolones for use only when there are no alternative antibacterial treatments available in patients at risk for aortic dissection, including those with a history of aneurysm of the aorta or other blood vessels, peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients. Epidemiologic studies report an increased rate of aortic dissection within 2 months after quinolone use, particularly in elderly patients.
Geriatric adults may be at a higher risk of adverse events related to systemic quinolones. Geriatric adults may be more susceptible to drug-associated aortic dissection, and may also be at increased risk for drug-associated tendon effects, especially in those receiving concomitant treatment with corticosteroids. Older adults are also more likely to have decreased renal function and care should be taken in dose selection; it may be useful to monitor renal function.
Delafloxacin can cause dizziness and light-headedness; therefore, patients should know how they react to the drug before driving or operating machinery or engaging in an activity requiring mental alertness or coordination.
Blood glucose disturbances, including symptomatic hyperglycemia and hypoglycemia, have been reported in patients receiving systemic delafloxacin. Hypoglycemia, sometimes resulting in coma, occurs more frequently in patients with diabetes mellitus who are receiving an oral hypoglycemic agent or insulin concomitantly with delafloxacin; carefully monitor blood glucose concentrations in these patients. Educate patients on the symptoms of hypoglycemia and how to treat if they experience hypoglycemia. Discontinue delafloxacin immediately if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Patients with diabetes may also be at an increased risk of developing detachment of the retina.
Published studies regarding adverse pregnancy outcomes with quinolone use during pregnancy have reported conflicting outcomes. Most systematic reviews and meta-analyses of observational studies have indicated no significant increases in rates of major malformations and adverse pregnancy outcomes for quinolone exposure during pregnancy. Some studies have demonstrated an increased risk of miscarriage or major malformations; however, some of these studies had significant methodological limitations, which could have led to a higher risk. The manufacturer states that limited data with delafloxacin use in human pregnancy are insufficient to inform a drug-associated risk.
There are no data available on the presence of delafloxacin in breast milk, the effects on the breast-fed infant, or the effects on milk production. Delafloxacin is excreted in the breast milk of rats. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for delafloxacin and any potential adverse effects on the breast-fed infant from delafloxacin or the underlying maternal condition.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Chlamydophila pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus haemolyticus, Staphylococcus lugdunesis, Streptococcus agalactiae (group B streptococci), Streptococcus anginosus, Streptococcus constellatus, Streptococcus dysgalactiae, Streptococcus intermedius, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of skin and skin structure infections:
Oral dosage:
Adults: 450 mg PO every 12 hours for 5 to 14 days.
Intravenous dosage:
Adults: 300 mg IV every 12 hours for 5 to 14 days.
For the treatment of community-acquired pneumonia (CAP):
Oral dosage:
Adults: 450 mg PO every 12 hours for a total duration of 5 to 10 days.
Intravenous dosage:
Adults: 300 mg IV every 12 hours for a total duration of 5 to 10 days.
Maximum Dosage Limits:
-Adults
900 mg/day PO or 600 mg/day IV.
-Geriatric
900 mg/day PO or 600 mg/day IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
If serum creatinine concentration increases in patients receiving intravenous delafloxacin, consider switching to oral therapy.
Renal dosing is based on estimated Glomerular Filtration Rate (eGFR) as calculated by the MDRD equation:
eGFR 30 mL/minute/1.73m2 or more: No dosage adjustment is needed.
eGFR 15 to 29 mL/minute/1.73m2: 200 mg IV every 12 hours. No dosage adjustment is needed for oral formulation.
eGFR less than 15 mL/minute/1.73m2: Use is not recommended due to insufficient information. In delafloxacin patients with severe renal impairment or end-stage renal disease (ESRD), accumulation of the intravenous vehicle, sulfobutylether-beta-cyclodextrin (SBECD) occurs.
Intermittent hemodialysis
Use is not recommended due to insufficient information. Hemodialysis removes approximately 19% of delafloxacin and 56% of sulfobutylether-beta-cyclodextrin (SBECD).
*non-FDA-approved indication
Acarbose: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including alpha-glucosidase inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Acetaminophen; Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Albuterol; Budesonide: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Alogliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including alpha-glucosidase inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Aluminum Hydroxide: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids containing aluminum hydroxide.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids containing aluminum hydroxide.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids containing aluminum hydroxide. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids containing aluminum hydroxide. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids containing aluminum hydroxide. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium trisilicate. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Amlodipine; Celecoxib: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Betamethasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Budesonide: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Budesonide; Formoterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Bupivacaine; Meloxicam: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Calcium Acetate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Magnesium Hydroxide: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Simethicone: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Chloride: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Gluconate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium; Vitamin D: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Celecoxib: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Celecoxib; Tramadol: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Chlorpheniramine; Pseudoephedrine: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Choline Salicylate; Magnesium Salicylate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium salicylate. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Chromium: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Cortisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Deflazacort: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dexamethasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Diclofenac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Diclofenac; Misoprostol: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Didanosine, ddI: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after didanosine tablets or powder for oral solution. Delafloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with delafloxacin.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Diflunisal: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Diphenhydramine; Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Diphenhydramine; Naproxen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etodolac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fenoprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ferric Maltol: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
Fludrocortisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Flurbiprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Hydrocodone; Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Hydrocortisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ibuprofen; Famotidine: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ibuprofen; Oxycodone: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ibuprofen; Pseudoephedrine: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Indomethacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Iron Salts: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
Iron: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ketoprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ketorolac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Lanthanum Carbonate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after lanthanum carbonate. When oral quinolones are given for short courses, consider eliminating the lanthanum carbonate doses that would be normally scheduled near the time of quinolone intake. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Linagliptin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Magnesium Citrate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium citrate. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Magnesium Hydroxide: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium hydroxide. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain magnesium hydroxide.
Magnesium Salicylate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after products that contain magnesium salicylate. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Magnesium Salts: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer quinolones at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of quinolones may be reduced by chelation with magnesium sulfate.
Magnesium: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium.
Meclofenamate Sodium: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Mefenamic Acid: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Meglitinides: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including meglitinides, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Meloxicam: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Metformin; Repaglinide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including meglitinides, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methylprednisolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Miglitol: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including alpha-glucosidase inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Nabumetone: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Naproxen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Naproxen; Esomeprazole: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Naproxen; Pseudoephedrine: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Nateglinide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including meglitinides, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Nonsteroidal antiinflammatory drugs: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oxaprozin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Piroxicam: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Polycarbophil: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after calcium polycarbophil. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Polyethylene Glycol; Electrolytes: (Major) Administer quinolones at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of quinolones may be reduced by chelation with magnesium sulfate.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer quinolones at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of quinolones may be reduced by chelation with magnesium sulfate.
Polysaccharide-Iron Complex: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
Pramlintide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including pramlintide, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Prednisolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Prednisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Pyridoxine, Vitamin B6: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Quinapril: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after quinapril tablets, which contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after quinapril tablets, which contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Repaglinide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including meglitinides, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sevelamer: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after sevelamer. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sucralfate: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after sucralfate. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with sucralfate. This interaction appears to be the result of chelation by the aluminum content of sucralfate.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulindac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Sumatriptan; Naproxen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tolmetin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Triamcinolone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Vitamin D: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Zinc Salts: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Zinc: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Delafloxacin is bactericidal via inhibition of DNA gyrase (topoisomerase II), an enzyme responsible for counteracting the excessive supercoiling of DNA during replication or transcription, and topoisomerase IV, an enzyme that helps separate the daughter DNA molecules. In gram-negative bacteria, the primary target is the DNA gyrase A subunit, while the primary target in gram-positive bacteria is generally topoisomerase IV. Delafloxacin is a dual targeting quinolone that has equally potent binding to both DNA-gyrase and topoisomerase IV. Additionally, delafloxacin has an anionic structure and is weakly acidic, which distinguishes it from other fluoroquinolones, such as moxifloxacin, which is zwitterionic or neutral. This enhances its antibacterial potency in environments with reduced pH, such as those found in phagolysosomes and infection sites containing inflammatory cells. Whereas MICs for other quinolones, such as ciprofloxacin and moxifloxacin, increase as the pH decreases, MICs for delafloxacin shift even lower at decreased pH. Uptake of delafloxacin is significant in both bacteria and eukaryotic cells, a property further enhanced at acidic pH, thus making delafloxacin more potent against S. aureus, both intracellularly and extracellularly. Once inside the bacteria cell, where pH is neutral, delafloxacin will be deprotonated (ionized) and less diffusible than moxifloxacin and therefore will remain inside the bacterial cell exerting its bactericidal actions. Delafloxacin exhibits concentration-dependent pharmacodynamics where the ratio of area under the concentration curve of free delafloxacin to minimal inhibitory concentration (free AUC:MIC) appears to best correlate with antibacterial activity.
The susceptibility interpretive criteria for delafloxacin is delineated by pathogen. The MICs are defined for methicillin-resistant S. aureus (MRSA), S. haemolyticus, E. coli, K. pneumoniae, and E. cloacae as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. The MICs are defined for S. lugdunensis as susceptible at 0.03 mcg/mL or less. The MICs are defined for S. pyogenes, S. anginosus Group, and H. parainfluenzae as susceptible at 0.06 mcg/mL or less. The MICS are defined for S. agalactiae as susceptible at 0.06 mcg/mL or less, intermediate at 0.12 mcg/mL, and resistant at 0.25 mcg/mL or more. The MICs are defined for E. faecalis as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 mcg/mL, and resistant at 0.5 mcg/mL or more. The MICs are defined for P. aeruginosa as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for S. pneumoniae as susceptible at 0.03 mcg/mL or less. The MICs are defined for H. influenzae as susceptible at 0.004 mcg/mL or less. The MICs for methicillin-sensitive S. aureus (MSSA) are determined by site of infection. For acute bacterial skin and skin structure infections (ABSSSI), the MICs for MSSA are defined as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. For community-acquired pneumonia (CAP), the MICs for MSSA are defined as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 mcg/mL, and resistant at 0.5 mcg/mL or more.
Resistance to quinolones, including delafloxacin, can occur due to multiple-step mutations in defined regions of the target bacterial enzymes topoisomerase IV and DNA gyrase, referred to as Quinolone-Resistance Determining Regions (QRDRs), or through altered efflux. Although cross-resistance between delafloxacin and other quinolones has been observed, some isolates resistant to other quinolones may be susceptible to delafloxacin. Since delafloxacin is a dual targeting quinolone that has equally potent binding to both DNA-gyrase and topoisomerase IV, while other quinolones preferentially bind to 1 or the other, the development of resistant strains may be reduced. Delafloxacin's intrinsic activity is higher than other quinolones; therefore, the impact of target mutations is not as impactful. Additionally, since delafloxacin does not become a zwitterion, it appears to be retained within the bacteria better than other quinolones. Delafloxacin also appears to be a poor substrate for efflux pumps. Compared to other quinolones, the concentrations preventing the selection of mutants (MPCs) are low, ranging 1 to 4 times the initial MIC, and 8 to 32-fold lower than other quinolones.
Delafloxacin is administered orally and intravenously. The plasma protein binding of delafloxacin is approximately 84%, and it binds primarily to albumin. Plasma protein binding is not significantly altered by renal impairment. The volume of distribution is 30 to 48 L, which approximates to total body water. After administration of 7 doses of delafloxacin 300 mg to healthy volunteers (n = 30), the mean delafloxacin AUC0-12 in alveolar macrophages was 80% of the free-plasma AUC0-12 and the mean AUC0-12 in epithelial lining fluid was 70% of the free-plasma AUC0-12.
Renal clearance of delafloxacin accounts for 35% to 45% of the total clearance. Glucuronidation is the primary metabolic pathway with oxidative metabolism representing about 1% of an administered dose. The glucuronidation is mediated mainly by UGT1A1, UGT1A3, and UGT2B15. Unchanged parent drug is the predominant component in plasma. There are no significant circulating metabolites. After a single IV dose, 65% was excreted in urine as unchanged delafloxacin and glucuronide metabolites and 28% was excreted in the feces as unchanged delafloxacin. After a single oral dose, 50% was excreted in urine as unchanged delafloxacin and glucuronide metabolites and 48% was excreted in the feces as unchanged delafloxacin. The mean half-life of delafloxacin was 3.7 hours after a single IV dose with a range from 4.2 to 8.5 hours after multiple oral doses.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP3A4, UGT1A1, UGT1A3, UGT2B15, P-gp, BCRP
Glucuronidation of delafloxacin is mediated mainly by UGT1A1, UGT1A3, and UGT2B15; however, glucuronidation represents 1% of the administered dose. In vitro, delafloxacin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); however, the clinical relevance of coadministration with inhibitors of these transporters is unknown. At clinically relevant concentrations, delafloxacin was a mild inducer of CYP2C9 and CYP3A4 in human hepatocytes. However, delafloxacin did not affect Cmax and AUC of midazolam (a sensitive CYP3A4 substrate). In vitro, at concentrations higher than clinically relevant, delafloxacin increased the activity of CYP2E1.
-Route-Specific Pharmacokinetics
Oral Route
The absolute bioavailability of delafloxacin after a single 450 mg oral dose was 58.8%. The AUC after a single 450 mg oral dose was comparable to that of a single 300 mg IV dose. Cmax was achieved within about 1 hour after oral administration under fasting conditions. Food did not affect the bioavailability of delafloxacin. Steady state was achieved within 3 days with an accumulation of approximately 36%.
Intravenous Route
The AUC after a single 450 mg oral dose was comparable to that of a single 300 mg IV dose. Steady state was achieved within 3 days with an accumulation of approximately 10%.
-Special Populations
Hepatic Impairment
No clinically meaningful changes in delafloxacin Cmax and AUC were observed after administration of a single 300 mg IV dose to patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C) compared to healthy controls.
Renal Impairment
The mean total exposure compared to matched controls after a single 400 mg oral dose was 1.5-fold higher in patients with moderate (eGFR 31 to 50 mL/minute/1.73 m2) and severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2). Total systemic exposure in patients with mild renal impairment (eGFR 51 to 80 mL/minute/1.73 m2) was comparable to healthy patients.
The mean total exposure compared to matched controls after a single 300 mg IV dose was 1.3-fold higher in patients with mild renal impairment (eGFR 51 to 80 mL/minute/1.73 m2), 1.6-fold higher in patients with moderate renal impairment (eGFR 31 to 50 mL/minute/1.73 m2), and 1.8-fold higher in patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2). In end-stage renal disease (ESRD) patients on hemodialysis, the mean total exposure was 2.1- and 2.6-fold higher for those receiving the dose within 1 hour before and 1 hour after dialysis, respectively, as compared to healthy controls. The mean dialysate clearance of delafloxacin was 4.21 L/hour (SD 1.56 L/hour). After about 4 hours of hemodialysis, the mean fraction of administered delafloxacin recovered in the dialysate was approximately 19%.
In patients with moderate renal impairment (eGFR 31 to 50 mL/minute/1.73 m2), severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2), or ESRD on hemodialysis, the accumulation of the intravenous vehicle, sulfobutylether-beta-cyclodextrin (SBECD), occurs. The mean systemic exposure (AUC) as compared to healthy controls increased 2-fold in patients with moderate impairment and 5-fold in patients with severe impairment. In ESRD patients on hemodialysis, the mean systemic exposure was 7.5- and 27-fold higher for those receiving the dose within 1 hour before and 1 hour after dialysis, respectively, as compared to healthy controls. In ESRD patients undergoing hemodialysis, SBECD is dialyzed at a clearance of 4.74 L/hour. When hemodialysis occurred 1 hour after the dose, the mean fraction of SBECD recovered in the dialysate was 56.1% over approximately 4 hours.
Geriatric
Delafloxacin pharmacokinetics were not significantly impacted by age. After a single 250 mg oral dose, the mean Cmax and AUC in elderly patients (65 years and older) were about 35% higher compared to young adults (18 to 40 years). This difference was not considered clinically relevant.
Gender Differences
Delafloxacin pharmacokinetics were not significantly impacted by gender. After the administration of a 250 mg oral dose, the mean Cmax and AUC values in male patients were comparable to female patients. Females have a 24% lower AUC than males; however, this difference is not considered clinically relevant.
Ethnic Differences
Delafloxacin pharmacokinetics were not significantly impacted by race.
Obesity
Delafloxacin pharmacokinetics were not significantly impacted by weight or body mass index.
Other
Delafloxacin pharmacokinetics were not significantly impacted by infectious disease state (ABSSSI and CABP).