7 DRUG INTERACTIONS The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with tinidazole: Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need adjustment during and up to 8 days after tinidazole therapy ( 7.1 ) Alcohol-containing beverages/preparations: Avoid during and up to 3 days after tinidazole therapy ( 7.1 ) Lithium: Monitor serum lithium concentrations ( 7.1 ) Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) Fluorouracil: Monitor for fluorouracil-associated toxicities ( 7.1 ) Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1 , 7.2 ) CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions ( 7.2 ) Although not specifically identified in studies with tinidazole, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole.
Source: FDA drug label - tinidazole
( 5.14 , 7.5 ) Antacids, Multivitamins or Dairy Products: Decreased absorption of Bismuth Subcitrate Potassium, Metronidazole and Tetracycline Hydrochloride Capsules; do not take concomitantly. ( 7.7 ) CYP inducers and CYP inhibitors: Prolonged or accelerated half-life of metronidazole or concomitant medications; use with caution. ( 7.8 , 7.9 ) 7.1 Disulfiram Psychotic reactions have been reported in alcoholic patients who are using metronidazole, a component of bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride and disulfiram concurrently.
Source: FDA drug label - bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride
Monitor for increased toxicities in patients receiving radiation therapy or drugs known to cause: • Myelosuppression and/or immunosuppression [ see Warnings and Precautions ( 5.1 ) ] • Nephrotoxicity including hemorrhagic cystitis [ see Warnings and Precautions ( 5.2 ) ] • Cardiotoxicity [ see Warnings and Precautions ( 5.3 ) ] • Pulmonary toxicity [ see Warnings and Precautions ( 5.4 ) ] • Secondary malignancies [ see Warnings and Precautions ( 5.5 ) ] • Hepatotoxicity including liver necrosis and VOD [ see Warnings and Precautions ( 5.6 ) ] 7.3 Effect of Cyclophosphamide on Other Drugs Metronidazole Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Monitor for neurologic toxicities in patients receiving metronidazole.
Source: FDA drug label - cyclophosphamide for injection
7.3 Drugs which Cause Peripheral Neuropathy The use of drugs which cause peripheral neuropathy (e.g., bortezomib, amiodarone, cisplatin, docetaxel, paclitaxel, vincristine, disulfiram, phenytoin, metronidazole, alcohol) can cause an additive effect and should be used with caution.
Source: FDA drug label - thalidomide
albuterol, systemic and inhaled amoxicillin ampicillin, with or without sulbactam atenolol azithromycin caffeine, dietary ingestion cefaclor co-trimoxazole (trimethoprim and sulfamethoxazole) diltiazem dirithromycin enflurane famotidine felodipine finasteride hydrocortisone isoflurane isoniazid isradipine influenza vaccine ketoconazole lomefloxacin mebendazole medroxyprogesterone methylprednisolone metronidazole metoprolol nadolol nifedipine nizatidine norfloxacin ofloxacin omeprazole prednisone, prednisolone ranitidine rifabutin roxithromycin sorbitol (purgative doses do not inhibit theophylline absorption) sucralfate terbutaline, systemic terfenadine tetracycline tocainide The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline.
Source: FDA drug label - aminophylline
7 DRUG INTERACTIONS 7.1 Disulfiram Psychotic reactions have been reported in patients who are concurrently taking disulfiram and nitroimidazole agents (structurally related to benznidazole, but not with benznidazole).
Source: FDA drug label - benznidazole
7 DRUG INTERACTIONS Drugs that Decrease Busulfan Clearance: Metronidazole, itraconazole, iron chelating agents, acetaminophen. Metronidazole decreases the clearance of busulfan to a greater extent than does itraconazole; metronidazole coadministration has been associated with increased busulfan toxicity.
Source: FDA drug label - busulfan
Drug Interactions Cimetidine tablets, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline, and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.
Source: FDA drug label - cimetidine
Drug Interactions Cimetidine, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.
Source: FDA drug label - cimetidine hydrochloride
(See PRECAUTIONS .) The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly.
Source: FDA drug label - ciprofloxacin
Metronidazole: Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity.
Source: FDA drug label - cyclophosphamide
Metronidazole Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity.
Source: FDA drug label - cyclophosphamide injection, solution
( 7.3 ) 7.1 Disulfiram and Metronidazole Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole). Discontinue products containing disulfiram or metronidazole at least 14 days before starting treatment with dronabinol oral solution and do not administer these products within 7 days of completing treatment with dronabinol oral solution [see Contraindications (4) , Warnings and Precautions (5.3) ] .
Source: FDA drug label - dronabinol
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.
Source: FDA drug label - infliximab
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.
Source: FDA drug label - infliximab-axxq
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.
Source: FDA drug label - infliximab-dyyb
Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance.
Source: FDA drug label - lithium
Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance.
Source: FDA drug label - lithium carbonate
Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance.
Source: FDA drug label - lithium citrate
Disulfiram/metronidazole Lopinavir and ritonavir oral solution contains alcohol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole).
Source: FDA drug label - lopinavir and ritonavir
Concurrent administration of any of the following drugs with lorazepam had no effect on the pharmacokinetics of lorazepam: metoprolol, cimetidine, ranitidine, disulfiram, propranolol, metronidazole, and propoxyphene.
Source: FDA drug label - lorazepam
7 DRUG INTERACTIONS Concomitant use of mebendazole and metronidazole should be avoided [see Warnings and Precautions (5.3) ] .
Source: FDA drug label - mebendazole
Drug interactions Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.
Source: FDA drug label - metronidazole topical
7 DRUG INTERACTIONS The intravaginal administration of a single dose of metronidazole vaginal gel results in lower systemic exposure to metronidazole that is approximately 2% to 4% of that achieved following oral administration of 500 mg metronidazole tablets [see Clinical Pharmacology ( 12.3 )]. The following drug interactions were reported for oral metronidazole. • Warfarin and other coumarin anticoagulants: Prolonged anticoagulant effects of warfarin and other coumarin anticoagulants have been reported with co-administration of oral metronidazole.
Source: FDA drug label - metronidazole vaginal gel, 1.3 %
Drug Interactions Drug interaction studies with mycophenolate mofetil have been conducted with acyclovir, antacids, cholestyramine, cyclosporine, ganciclovir, oral contraceptives, sevelamer, trimethoprim/sulfamethoxazole, norfloxacin, and metronidazole. Norfloxacin and Metronidazole Following single-dose administration of mycophenolate mofetil (1 g) to 11 healthy volunteers on day 4 of a 5 day course of a combination of norfloxacin and metronidazole, the mean MPA AUC 0-48h was significantly reduced by 33% compared to the administration of mycophenolate mofetil alone (p< 0.05). Therefore, mycophenolate mofetil is not recommended to be given with the combination of norfloxacin and metronidazole.
Source: FDA drug label - mycophenolate mofetil
( 7.5 ) Norfloxacin and Metronidazole: May decrease MPA concentrations; concomitant use with both drugs is not recommended. 7.6 Norfloxacin and Metronidazole MPA plasma concentrations may be decreased when MMF is administrated with norfloxacin and metronidazole. Therefore, mycophenolic acid delayed-release tablets are not recommended to be given with the combination of norfloxacin and metronidazole.
Source: FDA drug label - mycophenolic acid
There was no effect on neostigmine action on rocuronium reversal by cefuroxime, metronidazole, cefuroxime or metronidazole.
Source: FDA drug label - neostigmine methylsulfate
All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+ NADH).
Source: FDA drug label - metronidazole
Antialcoholics: disulfiram/ metronidazole Ritonavir formulations contain ethanol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole).
Source: FDA drug label - ritonavir
Antialcoholics: disulfiram/ metronidazole Ritonavir formulations contain ethanol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole).
Source: FDA drug label - ritonavir 100 mg
Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.* albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without methylprednisolone sulbactam metronidazole atenolol metoprolol azithromycin nadolol caffeine, dietary ingestion nifedipine cefaclor nizatidine co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin ofloxacin diltiazem omeprazole dirithromycin prednisone, prednisolone enflurane ranitidine famotidine rifabutin felodipine roxithromycin finasteride Sorbitol (purgative doses do not inhibit hydrocortisone theophylline absorption) isoflurane sucralfate isoniazid terbutaline, systemic isradipine terfenadine influenza vaccine tetracycline ketoconazole tocainide lomefloxacin * Refer to PRECAUTIONS, Drug Interactions for information regarding table.
Source: FDA drug label - theophylline
albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without sulbactam methylprednisolone atenolol metronidazole azithromycin metoprolol caffeine, dietary ingestion nadolol cefaclor nifedipine co-trimoxazole (trimethoprim and sulfamethoxazole) nizatidine diltiazem norfloxacin dirithromycin ofloxacin enflurane omeprazole famotidine prednisone, prednisolone felodipine ranitidine finasteride rifabutin hydrocortisone roxithromycin isoflurane Sorbitol (purgative doses do not inhibit theophylline absorption) isoniazid sucralfate isradipine terbutaline, systemic influenza vaccine terfenadine ketoconazole tetracycline lomefloxacin tocainide
Source: FDA drug label - theophylline anhydrous
Diltiazem Felodipine Nicardipine Nisoldipine Verapamil ↕ Diltiazem ↑ Felodipine (CYP3A substrate but not P-gp substrate) ↕ Nicardipine ↕ Nisoldipine (CYP3A substrate but not clear whether it is a P-gp substrate) ↕ Verapamil Disulfiram/Metronidazole Combination with TPV/ritonavir not studied APTIVUS capsules contain alcohol that can produce disulfiram-like reactions when co-administered with disulfiram or other drugs which produce this reaction (e.g., metronidazole).
Source: FDA drug label - tipranavir
7 DRUG INTERACTIONS The intravaginal administration of a single 5 gram dose of VANDAZOLE results in relatively lower mean systemic exposure to metronidazole that is approximately 2% to 5% of that achieved following a 500 mg oral dose of metronidazole [see Clinical Pharmacology ( 12.3 )] . VANDAZOLE should not be used by patients who have taken disulfiram within the last two weeks [see Contraindications ( 4.2 )] . Alcoholic beverages and preparations containing ethanol or propylene glycol should not be consumed during and for at least three days after VANDAZOLE therapy [see Contraindications ( 4.3 )] .
Source: FDA drug label - metronidazole
Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3.
Source: FDA drug label - warfarin
Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 .
Source: FDA drug label - warfarin sodium