Ciprofloxacin

Drug Interactions Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co­-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug. Table 11: Drugs That are Affected by and Affecting Ciprofloxacin Drugs That are Affected by Ciprofloxacin Drug(s) Recommendation Comments Tizanidine Contraindicated Concomitant administration of tizanidine and ciprofloxacin is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see CONTRAINDICATIONS (4.2)].

7 DRUG INTERACTIONS Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug. Table 8: Drugs That are Affected by and Affecting Ciprofloxacin Drugs That are Affected by Ciprofloxacin Drug(s) Recommendation Comments Tizanidine Contraindicated Concomitant administration of tizanidine and ciprofloxacin is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [ see Contraindications ( 4.2 ) ] Theophylline Avoid Use (Plasma Exposure Likely to be Increased and Prolonged) Concurrent administration of ciprofloxacin with theophylline may result in increased risk of a patient developing central nervous system (CNS) or other adverse reactions.

Quinolone antimicrobial that inhibits CYP1A2; should be avoided due to significant increase in duloxetine concentrations.

Moderate CYP3A4 inhibitor; concomitant use is contraindicated due to increased risk of hypotension and syncope.

Concomitant use of moderate CYP3A4 inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) has not been studied, but concomitant use with lomitapide is contraindicated since lomitapide exposure will likely increase significantly in the presence of these inhibitors.

[see Contraindications (4) and Clinical Pharmacology ( 12.3 ) ] 7.2 Ciprofloxacin Concomitant use of ciprofoxacin and tizanidine hydrochloride is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [See Contraindications (4) and Clinical Pharmacology ( 12.3 ) ] 7.3 CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of tizanidine hydrochloride with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided.

7.2 Ciprofloxacin Concomitant use of ciprofloxacin and Zanaflex is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )] . 7.3 CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of Zanaflex with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrhythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided.

7.2 Ciprofloxacin Concomitant use of ciprofloxacin and tizanidine is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )]. 7.3 CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin Because of potential drug interactions, concomitant use of tizanidine with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrhythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided.

Concurrent administration may reduce ciprofloxacin bioavailability by as much as 90%.

Co-administered calcium acetate decreased ciprofloxacin bioavailability by approximately 50% in a study of 15 healthy subjects. Administer ciprofloxacin at least one hour before or three hours after calcium acetate.

Products containing calcium may substantially decrease ciprofloxacin absorption, resulting in serum and urine levels considerably lower than desired.

Strong CYP1A2 inhibitor that increases clozapine plasma levels, potentially resulting in adverse reactions. Requires dose reduction to one-third.

Moderate CYP3A inhibitor. If short-term use unavoidable, reduce cobimetinib dose from 60 mg to 20 mg.

Chewable/buffered tablets or pediatric powder may substantially decrease ciprofloxacin absorption.

Quinolone antimicrobial and potent CYP1A2 inhibitor that should be avoided due to potential significant increase in duloxetine concentrations.

Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin).

Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin).

Co-administration may cause severe hypoglycemia and fatalities have been reported due to potentiation of glucose-lowering effect.

Co-administration may cause severe hypoglycemia and fatalities have been reported due to potentiation of glucose-lowering effect.

Products containing iron may substantially decrease ciprofloxacin absorption, resulting in serum and urine levels considerably lower than desired.

Lanthanum carbonate reduces bioavailability of ciprofloxacin by approximately 50%. Administer at least 1 hour before or 4 hours after lanthanum carbonate.

Concurrent administration may reduce ciprofloxacin bioavailability by as much as 90%.

Moderate CYP1A2 inhibitor that moderately increases pirfenidone exposure. Dosage reduction recommended if ciprofloxacin 750 mg twice daily cannot be avoided; monitor closely with lower doses.

Strong CYP1A2 inhibitor that may increase pomalidomide exposure and risk of toxicities. Avoid concomitant use; if unavoidable, reduce pomalidomide dose.

Concomitant use may increase risk of tendon rupture, especially in elderly patients. Rupture can occur during or after treatment.

Rasagiline plasma concentrations may increase up to 2-fold, potentially resulting in increased adverse events. Dose should not exceed 0.5 mg once daily.

CYP1A2 inhibitor increased ropinirole AUC by 84% and Cmax by 60%. Dose adjustment of ropinirole may be required.

Concurrent administration may substantially decrease ciprofloxacin absorption, resulting in serum and urine levels considerably lower than desired.

Concurrent administration may result in increased risk of CNS or other adverse reactions due to increased plasma exposure and prolonged levels.

CYP1A2 inhibitor that increases warfarin effect and INR; requires close INR monitoring

CYP1A2 inhibitor that increases warfarin effect and INR; requires close INR monitoring.

Products containing zinc may substantially decrease ciprofloxacin absorption, resulting in serum and urine levels considerably lower than desired.

Caffeine accumulation may occur when consumed with quinolones like ciprofloxacin.

CYP1A2 inhibitor may increase anagrelide exposure; monitor for cardiovascular events and titrate dose accordingly.

CYP1A2 inhibitor may increase anagrelide exposure; monitor for cardiovascular events and adjust dose.

Increase in anticoagulant effect with risk of elevated INR. Monitor prothrombin time and INR frequently during and after co-administration.

Strong CYP1A2 inhibitor that increases asenapine AUC and Cmax. Consider asenapine dose reduction based on clinical response.

Systemic quinolones including ciprofloxacin interfere with the metabolism of caffeine.

Co-administration of calcium acetate decreased ciprofloxacin bioavailability by approximately 50% in a 15-subject study. Administer one hour before or three hours after calcium acetate capsules.

CYP3A4 inhibitor that increases carbamazepine plasma levels. Close monitoring of carbamazepine levels and dosage adjustment may be required.

Co-administration may cause transient elevations in serum creatinine; monitor renal function.

Quinolone antimicrobial that inhibits CYP1A2 and may increase duloxetine concentrations.

Ciprofloxacin must be taken at least 2 hours before or after ferric citrate to avoid reduced bioavailability.

Ferric maltol may decrease bioavailability of ciprofloxacin. Separate administration by at least 4 hours and monitor clinical response.

Potentially may potentiate hypoglycemic action of glyburide; monitor closely for hypoglycemia.

Potentially potentiates hypoglycemic action of glyburide; monitor for hypoglycemia.

Drug Interactions with Other Drugs that Affect Itraconazole Concentrations Concomitant Drug Within Class Prevention or Management Drug Interactions with Other Drugs that Increase Itraconazole Concentrations and May Increase Risk of Adverse Reactions Associated with Itraconazole Antibacterials Ciprofloxacin a Erythromycin a Clarithromycin a Monitor for adverse reactions.

Exposure to ciprofloxacin may be increased when coadministered with leflunomide. Monitor and adjust dose as required.

Exposure of ciprofloxacin may be increased in patients taking leflunomide. Monitor and adjust dose as required.

Co-administration requires caution; ciprofloxacin may inhibit methotrexate elimination.

Ciprofloxacin may increase anticoagulant effect and INR; monitor prothrombin time.

Patiromer binds ciprofloxacin, potentially reducing systemic exposure and clinical efficacy. Separate dosing by at least 3 hours.

Strong CYP1A2 inhibitor that may increase exposure to pentoxifylline.

Ciprofloxacin may alter serum phenytoin levels (increased or decreased), risking seizure control loss or toxicity.

7 DRUG INTERACTIONS Moderate (e.g., ciprofloxacin) and strong inhibitors of CYP1A2 (e.g., fluvoxamine) increase systemic exposure of pirfenidone and may alter the adverse reaction profile of pirfenidone. Consider dosage reduction with use of ciprofloxacin. Moderate CYP1A2 Inhibitors Concomitant administration of pirfenidone and ciprofloxacin (a moderate inhibitor of CYP1A2) moderately increases exposure to pirfenidone [see Clinical Pharmacology ( 12.3 )] .

OAT3 substrate. Pretomanid inhibits OAT3 transporter, potentially increasing ciprofloxacin concentrations and adverse reactions. Monitor and consider dose reduction.

CYP1A2 substrate/inhibitor that may increase blood levels and/or toxicity of propranolol.

CYP1A2 inhibitor that may increase rasagiline plasma concentrations up to 2-fold, resulting in increased adverse events. Dose limit to 0.5 mg once daily.

Rifapentine may increase metabolism and decrease activity. Dosage adjustment may be necessary.

The concomitant use of strong or moderate CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin, fluvoxamine, methoxsalen, mexiletine, oral contraceptives, thiabendazole, vemurafenib, zileuton) with TIGLUTIK may increase the risk of TIGLUTIK - associated adverse reactions [see Clinical Pharmacology (12.3) ].

CYP1A2 inhibitor that increases AUC and Cmax of ropinirole; dose adjustment may be required.

Sevelamer Drug Interactions Oral drugs for which sevelamer did not alter the pharmacokinetics when administered concomitantly Digoxin Enalapril Iron Metoprolol Warfarin Oral drugs that have demonstrated interaction with sevelamer and are to be dosed separately from sevelamer carbonate Ciprofloxacin Mycophenolate mofetil Dosing Recommendations Take at least 2 hours before or 6 hours after sevelamer Take at least 2 hours before sevelamer • For oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy consider separation of the timing of administration and/or monitor clinical responses or blood levels of the concomitant medication. ( 7 ) • Sevelamer has demonstrated interaction with ciprofloxacin, mycophenolate mofetil, and therefore these drugs should be dosed separately from sevelamer carbonate.

Sevelamer Drug Interactions Oral drugs for which sevelamer did not alter the pharmacokinetics when administered concomitantly Digoxin Enalapril Iron Metoprolol Warfarin Oral drugs that have demonstrated interaction with sevelamer and are to be dosed separately from sevelamer carbonate Ciprofloxacin Mycophenolate mofetil Dosing Recommendations Take at least 2 hours before or 6 hours after sevelamer Take at least 2 hours before sevelamer • For oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy consider separation of the timing of administration and/or monitor clinical responses or blood levels of the concomitant medication. ( 7 ) • Sevelamer has demonstrated interaction with ciprofloxacin, mycophenolate mofetil, and therefore these drugs should be dosed separately from sevelamer carbonate.

Table 4: Sevelamer Drug Interactions Oral drugs for which sevelamer did not alter the pharmacokinetics when administered concomitantly Digoxin Enalapril Iron Metoprolol Warfarin Oral drugs that have demonstrated interaction with sevelamer and are to be dosed separately from sevelamer hydrochloride Dosing Recommendations Ciprofloxacin Mycophenolate mofetil Take at least 2 hours before or 6 hours after sevelamer Take at least 2 hours before sevelamer • When clinically significant drug interactions are expected, separate the timing of administration and monitor clinical responses or blood levels of the concomitant medication. ( 7 ) • Sevelamer binds ciprofloxacin and mycophenolate mofetil; dose these drugs separately from sevelamer hydrochloride.

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil).

Teriflunomide may increase exposure of ciprofloxacin. Monitor patients and adjust dose as required.

Dose adjustment is recommended with concomitant use of UBRELVY and moderate CYP3A4 inhibitors (e.g., cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice) [see Dosage and Administration ( 2.2 )] .

Co-administration had no effect on ivacaftor exposure. No dosage adjustment necessary.

Serum concentrations of ciprofloxacin and metronidazole were not altered when given concomitantly.

Co-administration of obiltoxaximab with intravenous or oral ciprofloxacin did not alter the pharmacokinetics of either drug.

CYP3A inhibitor not expected to have significant effect on prasugrel active metabolite pharmacokinetics.

Co-administration of raxibacumab with ciprofloxacin did not alter the pharmacokinetics of either drug.

No significant effect on tezacaftor or ivacaftor exposure; no dosage adjustment necessary.

70% increase Ciprofloxacin Similar to cimetidine.

7.4 Drug Interaction Studies Two pharmacokinetic studies evaluated the effects of co-administration of posaconazole (300 mg QD), ciprofloxacin (500 mg BID), amlodipine (5 to 10 mg QD), and carvedilol (20 to 40 mg QD) on the systemic levels of colchicine. GLOPERBA can be administered with amlodipine, carvedilol, and ciprofloxacin at the tested doses without a need for dose adjustment.

7.3 Drugs with No Clinically Significant Interactions with TRIKAFTA Ciprofloxacin Ciprofloxacin had no clinically relevant effect on the exposure of tezacaftor or ivacaftor and is not expected to affect the exposure of elexacaftor. Therefore, no dose adjustment is necessary during concomitant administration of TRIKAFTA with ciprofloxacin [see Clinical Pharmacology (12.3) ] .

Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of CD including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of CD including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of CD including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

Consider an alternative to these antibiotics, such as ciprofloxacin, azithromycin, and levofloxacin. 7.15 Concomitant Drugs That Do Not Need Dosage Adjustment No dosage adjustment of ORKAMBI or concomitant drug is recommended when ORKAMBI is given with the following: azithromycin, aztreonam, budesonide, ceftazidime, cetirizine, ciprofloxacin, colistimethate, colistin, dornase alfa, fluticasone, ipratropium, levofloxacin, pancreatin, pancrelipase, salbutamol, salmeterol, sulfamethoxazole, trimethoprim, tiotropium, and tobramycin.

Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in shorter time to reach maximum plasma concentrations.

7.10 Ciprofloxacin, Amoxicillin Plus Clavulanic Acid and Other Drugs That Alter the Gastrointestinal Flora Drugs that alter the gastrointestinal flora, such as ciprofloxacin or amoxicillin plus clavulanic acid may interact with MMF by disrupting enterohepatic recirculation. Interference of MPAG hydrolysis may lead to less MPA available for absorption when mycophenolic acid delayed-release tablets are concomitantly administered with ciprofloxacin or amoxicillin plus clavulanic acid.

Ciprofloxacin and Amoxicillin plus Clavulanic Acid A total of 64 mycophenolate mofetil-treated renal transplant recipients received either oral ciprofloxacin 500 mg bid or amoxicillin plus clavulanic acid 375 mg tid for 7 days or at least 14 days. Approximately 50% reductions in median trough MPA concentrations (pre-dose) from baseline (mycophenolate mofetil alone) were observed in 3 days following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid.

Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, felodipine, omeprazole, or quinine .

Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, diltiazem, felodipine, omeprazole , or quinine .

As with some other quinolones, concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentrations of theophylline and prolongation of its elimination half-life. Some quinolones, including ciprofloxacin, have also been shown to interfere with the metabolism of caffeine. Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium/aluminum antacids, sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, or products containing calcium, iron, or zinc may substantially decrease its absorption, resulting in serum and urine levels considerably lower than desired.

7 DRUG INTERACTIONS Table 1 Oral drugs that can be administered concomitantly with Velphoro Calcitriol Ciprofloxacin Digoxin Enalapril Furosemide HMG-CoA reductase inhibitors Hydrochlorothiazide Losartan Metoprolol Nifedipine Omeprazole Quinidine Warfarin Oral drugs that are to be separated from Velphoro Dosing Recommendations Doxycycline Acetylsalicylic acid Cephalexin Take at least 1 hour before Velphoro. Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG‑CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

70% increase Ciprofloxacin Similar to cimetidine.

7.3 Drugs with No Clinically Significant Interactions with ALYFTREK Ciprofloxacin No clinically relevant effect on the exposure of tezacaftor was observed when tezacaftor/ivacaftor was used concomitantly with ciprofloxacin [see Clinical Pharmacology (12.3) ] .