| Acid-reducing agents | Antacids may adsorb drugs in gastrointestinal tract, thus reducing absorption. Some antacids (eg, magnesium hydroxide with aluminum hydroxide) alkalinize the urine somewhat, thus altering excretion of drugs sensitive to urinary pH. H2-antagonists and proton-pump inhibitors can alter the absorption of drugs requiring gastric acidity for dissolution. | Antivirals: [P] Decreased absorption of antivirals that require acid for dissolution including atazanavir, fosamprenavir, indinavir, nelfinavir, rilpivirine. Azole antifungals: [P] Reduced gastrointestinal absorption of itraconazole, ketoconazole, and posaconazole due to increased gastric pH. Digoxin: [NP] Decreased gastrointestinal absorption of digoxin. Iron: [P] Decreased gastrointestinal absorption of iron with calcium-containing antacids. Kinase inhibitors: [P] Reduced gastrointestinal absorption of bosutinib, dabrafenib, dasatinib, erlotinib, idelalisib, and lapatinib due to increased gastric pH. Quinolones: [HP] Decreased gastrointestinal absorption of ciprofloxacin, norfloxacin, and enoxacin (and probably other quinolones). Rosuvastatin: [P] Decreased absorption of rosuvastatin. Salicylates: [P] Increased renal clearance of salicylates due to increased urine pH; occurs only with large doses of salicylates. Tetracyclines: [HP] Decreased gastrointestinal absorption of tetracyclines. Thyroxine: [NP] Reduced gastrointestinal absorption of thyroxine. |
| Alcohol | Chronic alcoholism results in enzyme induction. Acute alcoholic intoxication tends to inhibit drug metabolism (whether person is alcoholic or not). Severe alcohol-induced hepatic dysfunction may inhibit ability to metabolize drugs. Disulfiram-like reaction in the presence of certain drugs. Additive central nervous system depression with other central nervous system depressants. | Acetaminophen: [NE] Increased formation of hepatotoxic acetaminophen metabolites (in chronic alcoholics). Acitretin: [P] Increased conversion of acitretin to etretinate (teratogenic). Anticoagulants, oral: [NE] Increased hypoprothrombinemic effect with acute alcohol intoxication. Central nervous system depressants: [HP] Additive or synergistic central nervous system depression. Insulin: [NE] Acute alcohol intake may increase hypoglycemic effect of insulin (especially in fasting patients). Drugs that may produce a disulfiram-like reaction: Cephalosporins: [NP] Disulfiram-like reactions are noted with cefamandole, cefoperazone, cefotetan, and moxalactam. Chloral hydrate: [NP] Mechanism not established. Disulfiram: [HP] Inhibited aldehyde dehydrogenase. Metronidazole: [NP] Mechanism not established. Sulfonylureas: [NE] Chlorpropamide is most likely to produce a disulfiram-like reaction; acute alcohol intake may increase hypoglycemic effect (especially in fasting patients). |
| Allopurinol | Inhibits hepatic drug-metabolizing enzymes. Febuxostat will also inhibit the metabolism of azathioprine and mercaptopurine. | Anticoagulants, oral: [NP] Increased hypoprothrombinemic effect. Azathioprine: [P] Decreased azathioprine detoxification resulting in increased azathioprine toxicity. Mercaptopurine: [P] Decreased mercaptopurine metabolism resulting in increased mercaptopurine toxicity. |
| Anticoagulants, oral | Susceptible to induction and inhibition of CYP2C9 (warfarin), CYP3A4 (apixaban, rivaroxaban), and P-glycoprotein (apixaban, dabigatran, edoxaban, rivaroxaban). Warfarin highly bound to plasma proteins. Anticoagulation response altered by drugs that affect clotting factor synthesis or catabolism. | Drugs that may increase anticoagulant effect: Acetaminophen: [NE] Impaired synthesis of clotting factors at higher doses. Amiodarone: [P] Inhibited anticoagulant elimination. Anabolic steroids: [P] Altered clotting factor disposition? Azole antifungals: [P] Ketoconazole, itraconazole, voriconazole, and posaconazole can decrease apixaban, dabigatran, edoxaban, rivaroxaban, and perhaps warfarin elimination. Cimetidine: [HP] Decreased warfarin metabolism. Clopidogrel: [NP] Decreased warfarin metabolism and inhibits platelet function. Disulfiram: [P] Decreased warfarin metabolism. Efavirenz: [NP] Decreased warfarin metabolism. Fluconazole: [P] Decreased warfarin metabolism. Fluoxetine: [P] Decreased warfarin metabolism. Gemfibrozil: [NE] Mechanism not established. Lovastatin: [NP] Decreased warfarin metabolism. Macrolide antibiotics: [NP] Clarithromycin and erythromycin inhibit the metabolism of oral anticoagulants. Metronidazole: [P] Decreased warfarin metabolism. Miconazole: [NE] Decreased warfarin metabolism. Nonsteroidal anti-inflammatory drugs (NSAIDs): [HP] Inhibition of platelet function, gastric erosions; some agents increase hypoprothrombinemic response (unlikely with diclofenac, ibuprofen, or naproxen). Propafenone: [NE] Probably decreases anticoagulant elimination. Quinidine: [NP] Additive hypoprothrombinemia, decreased apixaban, dabigatran, edoxaban, rivaroxaban elimination. Ritonavir: [P] Decreased apixaban, dabigatran, edoxaban, rivaroxaban elimination. Salicylates: [HP] Platelet inhibition with aspirin but not with other salicylates; [P] large doses have hypoprothrombinemic effect. Simvastatin: [NP] Decreased warfarin metabolism. Sulfinpyrazone: [NE] Inhibited warfarin metabolism. Sulfonamides: [NE] Inhibited warfarin metabolism. Trimethoprim-sulfamethoxazole: [P] Decreased warfarin metabolism. Verapamil: [P] Decreased apixaban, dabigatran, edoxaban, rivaroxaban elimination. See also Alcohol; Allopurinol. Drugs that may decrease anticoagulant effect: Aminoglutethimide: [P] Increased metabolism of anticoagulant. Barbiturates: [P] Increased metabolism of anticoagulant. Bosentan: [P] Increased metabolism of anticoagulant. Carbamazepine: [P] Increased elimination of anticoagulant. Cholestyramine: [P] Reduced absorption of anticoagulant. Nafcillin: [NE] Increased metabolism of anticoagulant. Phenytoin: [NE] Increased metabolism of anticoagulant. Anticoagulant effect may increase transiently at start of phenytoin therapy due to protein-binding displacement of warfarin. Primidone: [P] Increased metabolism of anticoagulant. Rifabutin: [P] Increased elimination of anticoagulant. Rifampin: [P] Increased elimination of anticoagulant. St. John’s wort: [NE] Increased elimination of anticoagulant. Tipranavir: [NP] Increased elimination of apixaban, dabigatran, edoxaban, rivaroxaban. |
| Antidepressants, tricyclic and heterocyclic | Inhibition of transmitter uptake into 5-HT and NE neurons. Antimuscarinic effects may be additive with other antimuscarinic drugs. Susceptible to induction and inhibition of metabolism via CYP2D6, CYP3A4, and other CYP450 enzymes. | Amiodarone: [P] Decreased antidepressant metabolism. Expect similar interactions with dronedarone. Barbiturates: [P] Increased antidepressant metabolism. Bupropion: [NE] Decreased antidepressant metabolism. Carbamazepine: [NP] Enhanced metabolism of antidepressants. Cimetidine: [P] Decreased antidepressant metabolism. Clonidine: [P] Decreased clonidine antihypertensive effect. Diphenhydramine: [P] Decreased metabolism of antidepressants metabolized by CYP2D6. Guanadrel: [P] Decreased uptake of guanadrel into sites of action. Haloperidol: [P] Decreased metabolism of antidepressants metabolized by CYP2D6. Monoamine oxidase inhibitors (MAOIs): [NP] Some cases of excitation, hyperpyrexia, mania, and convulsions, especially with serotonergic antidepressants such as clomipramine and imipramine, but many patients have received combination without ill effects. Quinidine: [NP] Decreased metabolism of antidepressants metabolized by CYP2D6. Rifampin: [P] Increased antidepressant metabolism. Selective serotonin reuptake inhibitors (SSRIs): [P] Fluoxetine and paroxetine inhibit CYP2D6 and decrease metabolism of antidepressants metabolized by this enzyme (eg, desipramine). Citalopram, sertraline, and fluvoxamine are only weak inhibitors of CYP2D6, but fluvoxamine inhibits CYP1A2 and CYP3A4 and thus can inhibit the metabolism of antidepressants metabolized by these enzymes. Sympathomimetics: [P] Increased pressor response to norepinephrine, epinephrine, and phenylephrine. Terbinafine: [P] Decreased antidepressant metabolism. |
| Azole antifungals | Inhibition of CYP3A4 (itraconazole = ketoconazole > posaconazole > voriconazole > fluconazole). Inhibition of CYP2C9 (fluconazole, voriconazole). Inhibition of P-glycoprotein (itraconazole, ketoconazole, posaconazole). Susceptible to enzyme inducers (itraconazole, ketoconazole, voriconazole). | Antivirals: [P] Decreased metabolism of amprenavir, atazanavir, boceprevir, daclatasvir, darunavir, delavirdine, etravirine, fosamprenavir, indinavir, lopinavir, maraviroc, nelfinavir, rilpivirine, ritonavir, saquinavir, and tipranavir. Barbiturates: [P] Increased metabolism of itraconazole, ketoconazole, voriconazole. Benzodiazepines: [P] Decreased metabolism of alprazolam, midazolam, triazolam. Calcium channel blockers: [P] Decreased calcium channel blocker metabolism. Carbamazepine: [P] Decreased carbamazepine metabolism. Potential increased metabolism of itraconazole, ketoconazole, and voriconazole. Cisapride: [NP] Decreased metabolism of cisapride. Colchicine: [P] Decreased metabolism and transport of colchicine. Cyclosporine: [P] Decreased elimination of cyclosporine. Digoxin: [NE] Increased plasma concentrations of digoxin with itraconazole, posaconazole, and ketoconazole. Eplerenone: [P] Decreased metabolism of eplerenone. Ergot alkaloids: [P] Decreased metabolism of ergot alkaloids. HMG-CoA reductase inhibitors: [HP] Decreased metabolism of lovastatin, simvastatin, and, to a lesser extent, atorvastatin. Opioid analgesics: [P] Decreased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Quinidine: [P] Decreased metabolism of quinidine. Phenytoin: [P] Decreased metabolism of phenytoin with fluconazole and probably voriconazole. Phosphodiesterase inhibitors: [P] Decreased metabolism of phosphodiesterase inhibitor. Pimozide: [NE] Decreased pimozide metabolism. Rifabutin: [P] Decreased rifabutin metabolism. Increased metabolism of itraconazole, ketoconazole, and voriconazole. Rifampin: [P] Increased metabolism of itraconazole, ketoconazole, and voriconazole. Sirolimus: [P] Decreased elimination of sirolimus. Tacrolimus: [P] Decreased elimination of tacrolimus. See also Acid-Reducing Agents; Anticoagulants, oral. |
| Barbiturates | Induction of hepatic microsomal drug metabolizing enzymes and P-glycoprotein. Additive central nervous system depression with other central nervous system depressants. | Antivirals: Increased metabolism of antivirals amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir with barbiturates. Beta-adrenoceptor blockers: [P] Increased β-blocker metabolism. Calcium channel blockers: [P] Increased calcium channel blocker metabolism. Central nervous system depressants: [HP] Additive central nervous system depression. Corticosteroids: [P] Increased corticosteroid metabolism. Cyclosporine: [NE] Increased cyclosporine metabolism. Doxycycline: [P] Increased doxycycline metabolism. Estrogens: [P] Increased estrogen metabolism. Kinase inhibitors: [P] Increased metabolism of axitinib, bosutinib, ceritinib, cabozantinib, cobimetinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, ixazomib, lapatinib, nilotinib, nintedanib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ruxolitinib, sunitinib, tofacitinib, vandetanib, vemurafenib. Methadone: [NE] Increased methadone metabolism. Opioid analgesics: [P] Increased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Phenothiazine: [P] Increased phenothiazine metabolism. Phenytoin: [P] Increased phenytoin metabolism. Quinidine: [P] Increased quinidine metabolism. Sirolimus: [NE] Increased sirolimus metabolism. Tacrolimus: [NE] Increased tacrolimus metabolism. Theophylline: [NE] Increased theophylline metabolism. Valproic acid: [P] Decreased phenobarbital metabolism. See also Anticoagulants, oral; Antidepressants, tricyclic. |
| Beta-adrenoceptor blockers | Beta blockade (especially with noncardioselective agents such as propranolol) alters response to sympathomimetics with β-agonist activity (eg, epinephrine, albuterol). Beta blockers that undergo extensive first-pass metabolism may be affected by drugs capable of altering this process. | Drugs that may increase β-blocker effect: Amiodarone: [P] Decreased metabolism of β blockers metabolized by CYP2D6 (timolol, propranolol, nebivolol, metoprolol, carvedilol). Enhanced effects on myocardial conduction. Expect similar interactions with dronedarone. Cimetidine: [P] Decreased metabolism of β blockers that are cleared primarily by the liver, eg, propranolol. Less effect (if any) on those cleared by the kidneys, eg, atenolol, nadolol. Diphenhydramine: [P] Decreased metabolism of β blockers metabolized by CYP2D6 (timolol, propranolol, nebivolol, metoprolol, carvedilol). Haloperidol: [P] Decreased metabolism of β blockers metabolized by CYP2D6 (timolol, propranolol, nebivolol, metoprolol, carvedilol). Quinidine: [P] Decreased metabolism of β blockers metabolized by CYP2D6 (timolol, propranolol, nebivolol, metoprolol, carvedilol). Selective serotonin reuptake inhibitors (SSRIs): [P] Fluoxetine and paroxetine inhibit CYP2D6 and increase concentrations of timolol, propranolol, metoprolol, carvedilol, and nebivolol. Terbinafine: [P] Decreased metabolism of β blockers metabolized by CYP2D6 (timolol, propranolol, nebivolol, metoprolol, carvedilol). Drugs that may decrease β-blocker effect: Nonsteroidal anti-inflammatory drugs (NSAIDs): [P] Indomethacin reduces antihypertensive response; other prostaglandin inhibitors probably also interact. Effects of β blockers on other drugs: Clonidine: [NE] Hypertensive reaction if clonidine is withdrawn; this is more likely to occur with non-cardioselective beta blockers. Insulin: [P] Inhibition of glucose recovery from hypoglycemia; inhibition of symptoms of hypoglycemia (except sweating); increased blood pressure during hypoglycemia. Prazosin: [P] Increased hypotensive response to first dose of prazosin. Sympathomimetics: [P] Increased pressor response to epinephrine (and possibly other sympathomimetics); this is more likely to occur with noncardioselective β blockers. See also Barbiturates; Theophylline. |
| Bile acid-binding resins | Resins may bind with orally administered drugs in gastrointestinal tract. Resins may bind in gastrointestinal tract with drugs that undergo enterohepatic circulation, even if the latter are given parenterally. | Acetaminophen: [NE] Decreased gastrointestinal absorption of acetaminophen. Digitalis glycosides: [NE] Decreased gastrointestinal absorption of digitoxin (possibly also digoxin). Furosemide: [P] Decreased gastrointestinal absorption of furosemide. Methotrexate: [NE] Reduced gastrointestinal absorption of methotrexate. Mycophenolate: [P] Reduced gastrointestinal absorption of mycophenolate. Thiazide diuretics: [P] Reduced gastrointestinal absorption of thiazides. Thyroid hormones: [P] Reduced thyroid absorption. See also Anticoagulants, oral. |
| Calcium channel blockers | Verapamil, diltiazem, and perhaps nicardipine inhibit hepatic drug-metabolizing enzymes (CYP3A4) and P-glycoprotein. Metabolism (via CYP3A4) of diltiazem, felodipine, nicardipine, nifedipine, verapamil, and other calcium channel blockers subject to induction and inhibition. | Amiodarone: [P] Decreased metabolism of calcium channel blockers. Enhanced effects on myocardial conduction with bepridil, diltiazem, and verapamil. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of calcium channel blockers. Boceprevir: [P] Decreased metabolism of calcium channel blockers. Carbamazepine: [P] Decreased carbamazepine metabolism with diltiazem and verapamil; possible increase in calcium channel blocker metabolism. Cimetidine: [NP] Decreased metabolism of calcium channel blockers. Colchicine: [P] Decreased colchicine elimination with diltiazem, nicardipine, and verapamil. Conivaptan: [P] Decreased metabolism of calcium channel blockers. Cyclosporine: [P] Decreased cyclosporine elimination with diltiazem, nicardipine, verapamil. Digitalis glycosides: [P] Decreased elimination of digitalis glycoside with bepridil, diltiazem and verapamil. Kinase inhibitors: [P] Decreased metabolism of calcium channel blockers with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Decreased metabolism of kinase inhibitors by diltiazem, nicardipine, and verapamil. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the metabolism of calcium channel blockers. Phenytoin: [P] Increased metabolism of calcium channel blockers. Rifampin: [P] Increased metabolism of calcium channel blockers. Sirolimus: [P] Decreased sirolimus elimination with diltiazem, nicardipine, verapamil. Statins: [P] Decreased atorvastatin, lovastatin, and simvastatin elimination with diltiazem, nicardipine, verapamil. Tacrolimus: [P] Decreased tacrolimus elimination with diltiazem, nicardipine, verapamil. Theophylline: [P] Decreased theophylline metabolism with diltiazem, nicardipine, and verapamil. See also Azole antifungals; Barbiturates. |
| Carbamazepine | Induction of hepatic microsomal drug-metabolizing enzymes and P-glycoprotein. Susceptible to induction and inhibition of metabolism, primarily by CYP3A4. | Amiodarone: [P] Decreased metabolism of carbamazepine; increased metabolism of amiodarone. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of carbamazepine. Increased metabolism of antivirals by carbamazepine. Cimetidine: [P] Decreased carbamazepine metabolism. Corticosteroids: [P] Increased corticosteroid metabolism. Cyclosporine: [P] Increased cyclosporine metabolism and possible decreased carbamazepine metabolism. Danazol: [P] Decreased carbamazepine metabolism. Digitalis glycosides: [P] Increased digoxin elimination. Fluvoxamine: [NE] Decreased carbamazepine metabolism. Estrogens: [P] Increased estrogen metabolism. Haloperidol: [P] Increased haloperidol metabolism. Isoniazid: [P] Decreased carbamazepine metabolism. Kinase inhibitors: [P] Decreased metabolism of carbamazepine with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Increased metabolism of kinase inhibitors. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the metabolism of carbamazepine. Nefazodone: [NE] Decreased carbamazepine metabolism. Opioid analgesics: [P] Increased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Rifampin: [P] Increased carbamazepine metabolism. Selective serotonin reuptake inhibitors (SSRIs): [NE] Fluoxetine and fluvoxamine decrease carbamazepine metabolism. Sirolimus: [P] Increased sirolimus metabolism. St. John’s wort: [P] Increased carbamazepine metabolism. Tacrolimus: [P] Increased tacrolimus metabolism. Theophylline: [NE] Increased theophylline metabolism. See also Anticoagulants, oral; Antidepressants, tricyclic; Azole antifungals; Calcium channel blockers. |
| Cimetidine | Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not.) May inhibit the renal tubular secretion of weak bases. | Antivirals: [P] Decreased metabolism of amprenavir, atazanavir, boceprevir, daclatasvir, darunavir, delavirdine, etravirine, fosamprenavir, indinavir, lopinavir, maraviroc, nelfinavir, rilpivirine, ritonavir, saquinavir, and tipranavir. Benzodiazepines: [P] Decreased metabolism of alprazolam, chlordiazepoxide, diazepam, halazepam, prazepam, and clorazepate but not oxazepam, lorazepam, or temazepam. Carmustine: [NE] Increased bone marrow suppression. Dofetilide: [NP] Decreased renal excretion of dofetilide. Lidocaine: [P] Decreased metabolism of lidocaine. Opioid analgesics: [P] Decreased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Phenytoin: [NE] Decreased phenytoin metabolism. Procainamide: [P] Decreased renal excretion of procainamide. Quinidine: [P] Decreased metabolism of quinidine. Theophylline: [P] Decreased theophylline metabolism. See also Anticoagulants, oral; Antidepressants, tricyclic; Azole antifungals; β-Adrenoceptor blockers; Calcium channel blockers; Carbamazepine. |
| Cisapride | Susceptible to induction and inhibition of metabolism by CYP3A4 inhibitors. High cisapride serum concentrations can result in ventricular arrhythmias. | Amiodarone: [NP] Decreased cisapride metabolism. Expect similar interaction with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of cisapride. Cobicistat: [P] Decreased metabolism of cisapride. Conivaptan: [P] Decreased metabolism of cisapride. Cyclosporine: [NE] Decreased metabolism of cisapride. Kinase inhibitors: [P] Decreased metabolism of cisapride with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the metabolism of cisapride. Nefazodone: [NP] Decreased metabolism of cisapride by CYP3A4. Ritonavir: [P] Decreased metabolism of cisapride. Selective serotonin reuptake inhibitors (SSRIs): [NP] Fluvoxamine reduces cisapride metabolism. See also Azole antifungals. |
| Colchicine | Susceptible to changes in CYP3A4 metabolism and P-glycoprotein transport. | Amiodarone: [NP] Decreased colchicine metabolism and transport. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of colchicine. Carbamazepine: [P] Increased metabolism of colchicine. Cobicistat: [P] Decreased metabolism of colchicine. Conivaptan: [P] Decreased metabolism of colchicine. Cyclosporine: [P] Decreased colchicine elimination. Kinase inhibitors: [P] Decreased metabolism of colchicine with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the metabolism of colchicine. Nefazodone: [NE] Decreased colchicine metabolism. Rifampin: [P] Increased colchicine metabolism. St. John’s wort: [NP] Increased colchicine metabolism. See also Azole antifungals; Calcium channel blockers. |
| Cyclosporine | Susceptible to induction and inhibition of elimination by CYP3A4 and P-glycoprotein. (Tacrolimus and sirolimus appear to have similar interactions.) | Aminoglycosides: [NE] Possible additive nephrotoxicity. Amphotericin B: [NE] Possible additive nephrotoxicity. Cidofovir: [NE] Possible additive nephrotoxicity. Drugs that may increase cyclosporine effect: Amiodarone: [P] Decreased cyclosporine elimination. Expect similar interaction with dronedarone. Androgens: [NE] Increased serum cyclosporine concentration. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the elimination of cyclosporine. Cobicistat: [P] Decreased cyclosporine elimination. Conivaptan: [P] Decreased cyclosporine elimination. Kinase inhibitors: [P] Decreased metabolism of cyclosporine with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Cyclosporine reduces metabolism of kinase inhibitors. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the elimination of cyclosporine. Nefazodone: [P] Decreased cyclosporine metabolism. Quinupristin: [P] Decreased cyclosporine metabolism. Statins: [NP] Decreased metabolism of atorvastatin, lovastatin, and simvastatin. Myopathy and rhabdomyolysis noted in patients taking statins and cyclosporine. Drugs that may decrease cyclosporine effect: Bosentan: [P] Increased cyclosporine elimination. Dexamethasone: [NP] Increased cyclosporine metabolism. Efavirenz: [P] Increased cyclosporine metabolism. Etravirine: [NP] Increased cyclosporine metabolism. Nevirapine: [NP] Increased cyclosporine metabolism. Phenytoin: [P] Increased cyclosporine metabolism. Rifabutin: [NP] Increased cyclosporine metabolism. Rifampin: [P] Increased cyclosporine elimination. St. John’s wort: [NP] Increased cyclosporine elimination. See also Azole antifungals; Barbiturates; Calcium channel blockers; Carbamazepine. |
| Digitalis glycosides | Digoxin susceptible to alteration of gastrointestinal absorption. Renal and nonrenal excretion of digoxin susceptible to inhibition. Digitalis toxicity may be increased by drug-induced electrolyte imbalance (eg, hypokalemia). | Drugs that may increase digitalis effect: Amiodarone: [P] Increased digoxin plasma concentrations. Expect similar interaction with dronedarone. Antivirals: [P] Daclatasvir, indinavir, nelfinavir, paritaprevir, ritonavir, saquinavir, and telaprevir reduce the elimination of digoxin. Conivaptan: [P] Increased digoxin plasma concentrations. Cyclosporine: [P] Increased digoxin plasma concentrations. Macrolide antibiotics: [P] Azithromycin, clarithromycin, and erythromycin inhibit the elimination of digoxin. Potassium-depleting drugs: [P] Increases likelihood of digitalis toxicity. Propafenone: [P] Increases digoxin plasma concentrations. Quinidine: [HP] Increased digoxin plasma concentrations; displaces digoxin from tissue binding sites. Spironolactone: [NE] Increased digoxin plasma concentrations. Tacrolimus: [P] Increased digoxin plasma concentrations. Ticagrelor: [P] Increased digoxin plasma concentrations. See also Azole antifungals; Calcium channel blockers. Drugs that may decrease digitalis effect: Kaolin-pectin: [P] Decreased gastrointestinal digoxin absorption. Rifampin: [NE] Increased metabolism of digitoxin and elimination of digoxin. St. John’s wort: [NP] Increased digoxin elimination. Sulfasalazine: [NE] Decreased gastrointestinal digoxin absorption. See also Acid reducing agents; Bile acid-binding resins; Carbamazepine. |
| Disulfiram | Inhibits CYP2C9. Inhibits aldehyde dehydrogenase. | Benzodiazepines: [P] Decreased metabolism of chlordiazepoxide and diazepam but not lorazepam and oxazepam. Metronidazole: [NE] Confusion and psychoses reported in patients receiving this combination; mechanisms unknown. Phenytoin: [P] Decreased phenytoin metabolism. See also Alcohol; Anticoagulants, oral. |
| Estrogens | Estrogen metabolism (CYP3A4) susceptible to induction and inhibition. Enterohepatic circulation of estrogen may be interrupted by alteration in bowel flora (eg, due to antibiotics). | Ampicillin: [NP] Interruption of enterohepatic circulation of estrogen; possible reduction in oral contraceptive efficacy. Some other oral antibiotics may have a similar effect. Bexarotene: [P] Increased estrogen metabolism, possible reduction in oral contraceptive efficacy. Bosentan: [NP] Enzyme induction leading to reduced estrogen effect. Corticosteroids: [P] Decreased metabolism of corticosteroids leading to increased corticosteroid effect. Dexamethasone may increase estrogen metabolism. Efavirenz: [P] Increased estrogen metabolism, possible reduction in oral contraceptive efficacy. Griseofulvin: [NP] Increased estrogen metabolism, possible reduction in oral contraceptive efficacy. Nelfinavir: [P] Increased estrogen metabolism, possible reduction in oral contraceptive efficacy. Nevirapine: [NP] Increased estrogen metabolism, possible reduction in oral contraceptive efficacy. Phenytoin: [P] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. Primidone: [P] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. Rifabutin: [P] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. Rifampin: [P] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. St. John’s wort: [P] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. See also Barbiturates; Carbamazepine. |
| HMG-CoA reductase inhibitors (statins) | Lovastatin, simvastatin, and, to a lesser extent, atorvastatin are susceptible to CYP3A4 inhibitors and inducers; additive risk with other drugs that can cause myopathy. | Amiodarone: [NP] Decreased atorvastatin, lovastatin, and simvastatin metabolism. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of atorvastatin, lovastatin, and simvastatin. Bosentan: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. Carbamazepine: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. Clofibrate: [NP] Increased risk of myopathy. Cobicistat: [P] Decreased metabolism of atorvastatin, lovastatin, and simvastatin. Conivaptan: [P] Decreased metabolism of atorvastatin, lovastatin, and simvastatin. Cyclosporine: [P] Decreased atorvastatin, lovastatin, rosuvastatin, pitavastatin, and simvastatin elimination. Gemfibrozil: [NP] Increased plasma lovastatin and simvastatin and increased risk of myopathy. Kinase inhibitors: [P] Decreased metabolism of atorvastatin, lovastatin, and simvastatin by ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Macrolide antibiotics: [P] Clarithromycin and erythromycin inhibit the elimination of statins. Nefazodone: [NP] Decreased atorvastatin, lovastatin, and simvastatin metabolism. Phenytoin: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. Rifampin: [P] Increased atorvastatin, lovastatin, and simvastatin metabolism. St. John’s wort: [NP] Increased atorvastatin, lovastatin, and simvastatin metabolism. See also Azole antifungals; Calcium channel blockers; Cyclosporine. |
| Iron | Binds with drugs in gastrointestinal tract, reducing absorption. | Methyldopa: [NE] Decreased methyldopa absorption. Mycophenolate: [P] Decreased mycophenolate absorption. Quinolones: [P] Decreased absorption of ciprofloxacin and other quinolones. Tetracyclines: [P] Decreased absorption of tetracyclines; decreased efficacy of iron. Thyroid hormones: [P] Decreased thyroxine absorption. See also Antacids. |
| Levodopa | Levodopa degraded in gut prior to reaching sites of absorption. Agents that alter gastrointestinal motility may alter degree of intraluminal degradation. Antiparkinsonism effect of levodopa susceptible to inhibition by other drugs. | Clonidine: [NE] Inhibited antiparkinsonism effect. Haloperidol: [NP] Inhibited antiparkinsonism effect. Metoclopramide: [NP] Inhibited antiparkinsonism effect. Monoamine oxidase inhibitors (MAOIs): [P] Hypertensive reaction (carbidopa prevents the interaction). Papaverine: [NE] Inhibited antiparkinsonism effect. Phenothiazines: [P] Inhibited antiparkinsonism effect. Phenytoin: [NE] Inhibited antiparkinsonism effect. Pyridoxine: [P] Inhibited antiparkinsonism effect (carbidopa prevents the interaction). |
| Lithium | Renal lithium excretion sensitive to changes in sodium balance. (Sodium depletion tends to cause lithium retention.) Susceptible to drugs enhancing central nervous system lithium toxicity. | ACE inhibitors (ACEIs): [NE] Reduce renal clearance of lithium; increase lithium effect. Angiotensin II receptor blockers (ARBs): [NE] Reduce renal clearance of lithium; increase lithium effect. Diuretics (especially thiazides): [P] Decreased excretion of lithium; furosemide may be less likely to produce this effect than thiazide diuretics. Haloperidol: [NP] Occasional cases of neurotoxicity in manic patients, especially with large doses of one or both drugs. Methyldopa: [NE] Increased likelihood of central nervous system lithium toxicity. Nonsteroidal anti-inflammatory drugs (NSAIDs): [NE] Reduced renal lithium excretion (except sulindac and salicylates). Theophylline: [P] Increased renal excretion of lithium; reduced lithium effect. |
| Macrolides | The macrolides clarithromycin and erythromycin are known to inhibit CYP3A4 and P-glycoprotein. Azithromycin does not appear to inhibit CYP3A4 but is a modest inhibitor of P-glycoprotein. | Benzodiazepines: [P] Decreased metabolism of alprazolam, midazolam, triazolam. Eplerenone: [P] Decreased metabolism of eplerenone. Ergot alkaloids: [P] Decreased elimination of ergot alkaloids. Kinase inhibitors: [P] Decreased metabolism of axitinib, bosutinib, ceritinib, cabozantinib, cobimetinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, ixazomib, lapatinib, nilotinib, nintedanib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ruxolitinib, sunitinib, tofacitinib, vandetanib, and vemurafenib by clarithromycin and erythromycin. Opioid analgesics: [P] Decreased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Phosphodiesterase inhibitors: [P] Decreased metabolism of phosphodiesterase inhibitor. Pimozide: [P] Increased pimozide concentrations. Quinidine: [P] Increased serum quinidine concentrations. Theophylline: [P] Decreased metabolism of theophylline. See also Anticoagulants, oral; Calcium channel blockers; Carbamazepine; Cisapride; Colchicine; Cyclosporine; Digitalis glycosides; HMG-CoA reductase inhibitors. |
| Monoamine oxidase inhibitors (MAOIs) | Increased norepinephrine stored in adrenergic neuron. Displacement of these stores by other drugs may produce acute hypertensive response. MAOIs have intrinsic hypoglycemic activity. | Anorexiants: [P] Hypertensive episodes due to release of stored norepinephrine (benzphetamine, diethylpropion, mazindol, phendimetrazine, phentermine). Antidiabetic agents: [P] Additive hypoglycemic effect. Buspirone: [NE] Possible serotonin syndrome; avoid concurrent use. Dextromethorphan: [NP] Severe reactions (hyperpyrexia, coma, death) have been reported. Guanethidine: [P] Reversal of the hypotensive action of guanethidine. Mirtazapine: [NE] Possible serotonin syndrome; avoid concurrent use. Nefazodone: [NP] Possible serotonin syndrome; avoid concurrent use. Opioid analgesics: [NP] Some patients develop hypertension, rigidity, excitation; meperidine more likely to interact than morphine; avoid concurrent use. Phenylephrine: [P] Hypertensive episode, since phenylephrine is metabolized by monoamine oxidase. Selective serotonin reuptake inhibitors (SSRIs): [P] Fatalities have occurred due to serotonin syndrome; contraindicated in patients taking MAOIs; avoid concurrent use. Sibutramine: [NE] Possible serotonin syndrome; avoid concurrent use. Sympathomimetics (indirect-acting): [HP] Hypertensive episode due to release of stored norepinephrine (amphetamines, ephedrine, isometheptene, phenylpropanolamine, pseudoephedrine). Tramadol: [NP] Possible serotonin syndrome; avoid concurrent use. Venlafaxine: [NP] Possible serotonin syndrome; avoid concurrent use. See also Antidepressants, tricyclic and heterocyclic; Levodopa. |
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Prostaglandin inhibition may result in reduced renal sodium excretion, impaired resistance to hypertensive stimuli, and reduced renal lithium excretion. Most NSAIDs inhibit platelet function; may increase likelihood of bleeding due to other drugs that impair hemostasis. | ACE inhibitors (ACEIs): [P] Decreased antihypertensive response. Angiotensin II receptor blockers (ARBs): [P] Decreased antihypertensive response. Furosemide: [P] Decreased diuretic, natriuretic, and antihypertensive response to furosemide. Hydralazine: [NE] Decreased antihypertensive response to hydralazine. Methotrexate: [NP] Possibly increased methotrexate toxicity (especially with anticancer doses of methotrexate). Selective serotonin reuptake inhibitors (SSRIs): [P] Increased risk of bleeding due to platelet inhibition. Thiazide diuretics: [P] Decreased diuretic, natriuretic, and antihypertensive response. Triamterene: [NE] Decreased renal function noted with triamterene plus indomethacin in both healthy subjects and patients. See also Anticoagulants, oral; β-Adrenoceptor blockers; Lithium. |
| Opioid analgesics | Opioid analgesics that are substrates of CYP3A4 (alfentanil, fentanyl, oxycodone, sufentanil, and to a lesser extent methadone) are susceptible to inhibitors and inducers. Methadone is primarily metabolized by CYP2B6. Additive central nervous system depression with other central nervous system depressants. | Amiodarone: [NP] Decreased CYP3A4-dependent opioid metabolism. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of CYP3A4-dependent opioids. Boceprevir: [P] Decreased metabolism of CYP3A4-dependent opioids. Bosentan: [P] Increased CYP3A4-dependent opioid metabolism. Cobicistat: [P] Decreased metabolism of CYP3A4-dependent opioids. Conivaptan: [P] Decreased metabolism of CYP3A4-dependent opioids. Efavirenz: [P] Increased metabolism of CYP3A4-dependent opioids. Kinase inhibitors: [P] Decreased metabolism of CYP3A4-dependent opioid by ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Nefazodone: [NP] Decreased CYP3A4-dependent opioid metabolism. Nevirapine: [P] Increased metabolism of CYP3A4-dependent opioids. Phenytoin: [P] Increased CYP3A4-dependent opioid metabolism. Rifampin: [P] Increased CYP3A4-dependent opioid metabolism. St. John’s wort: [NP] Increased CYP3A4-dependent opioid metabolism. See also Azole antifungal agents; Barbiturates; Carbamazepine; Cimetidine; Macrolides; Monoamine oxidase inhibitors. |
| Phenytoin | Induces hepatic microsomal drug metabolism. Susceptible to inhibition of metabolism by CYP2C9 and, to a lesser extent, CYP2C19. | Drugs whose metabolism is stimulated by phenytoin: Corticosteroids: [P] Decreased serum corticosteroid levels. Doxycycline: [P] Decreased serum doxycycline levels. Mexiletine: [NE] Decreased serum mexiletine levels. Quinidine: [P] Decreased serum quinidine levels. Theophylline: [NP] Decreased serum theophylline levels. See also Calcium channel blockers; Cyclosporine; Estrogens; Opioid analgesics. Drugs that inhibit phenytoin metabolism: Amiodarone: [P] Increased serum phenytoin concentration; possible reduction in serum amiodarone concentration. Capecitabine: [NE] Increased phenytoin plasma concentrations. Chloramphenicol: [P] Increased phenytoin plasma concentrations. Felbamate: [P] Increased phenytoin plasma concentrations. Fluorouracil: [NE] Increased phenytoin plasma concentrations. Fluvoxamine: [NP] Increased phenytoin plasma concentrations. Isoniazid: [NP] Increased serum phenytoin; problem primarily with slow acetylators of isoniazid. Metronidazole: [NP] Increased phenytoin plasma concentrations. Sulfamethoxazole: [P] Increased phenytoin plasma concentrations. Ticlopidine: [NP] Increased phenytoin plasma concentrations. See also Azole antifungals; Cimetidine; Disulfiram. Drugs that enhance phenytoin metabolism: Bosentan: [P] Decreased phenytoin plasma concentrations. Carbamazepine: [P] Decreased phenytoin plasma concentrations. Rifampin: [P] Decreased phenytoin plasma concentrations. St. John’s wort: [P] Decreased phenytoin plasma concentrations. See also Barbiturates. |
| Pimozide | Susceptible to CYP3A4 inhibitors; may exhibit additive effects with other agents that prolong QTc interval. | Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of pimozide. Boceprevir: [P] Decreased metabolism of pimozide. Cobicistat: [P] Decreased metabolism of pimozide. Conivaptan: [P] Decreased metabolism of pimozide. Kinase inhibitors: [P] Decreased metabolism of pimozide with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Nefazodone: [NP] Decreased pimozide metabolism. See also Azole antifungals; Cyclosporine; Macrolides. |
| Potassium-sparing diuretics (amiloride, eplerenone, spironolactone, triamterene) | Additive effects with other agents increasing serum potassium concentration. Eplerenone is a substrate for CYP3A4 and is susceptible to inhibition and induction. May alter renal excretion of substances other than potassium (eg, digoxin, hydrogen ions). | ACE inhibitors (ACEIs): [NP] Additive hyperkalemic effect. Angiotensin II receptor blockers (ARBs): [NP] Additive hyperkalemic effect. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of eplerenone. Boceprevir: [P] Decreased metabolism of eplerenone. Cobicistat: [P] Decreased metabolism of eplerenone. Conivaptan: [P] Decreased metabolism of eplerenone. Kinase inhibitors: [P] Decreased metabolism of eplerenone with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Potassium-sparing diuretics: [P] Additive hyperkalemic effect. Potassium supplements: [P] Additive hyperkalemic effect; especially a problem in presence of renal impairment. See also Azole antifungals; Digitalis glycosides; Macrolides; Nonsteroidal anti-inflammatory drugs. |
| Probenecid | Interference with renal excretion of drugs that undergo active tubular secretion, especially weak acids. Inhibition of glucuronide conjugation of other drugs. | Clofibrate: [P] Reduced glucuronide conjugation of clofibric acid. Methotrexate: [P] Decreased renal methotrexate excretion; possible methotrexate toxicity. Pralatrexate: [P] Decreased renal pralatrexate excretion; possible pralatrexate toxicity. Penicillin: [P] Decreased renal penicillin excretion. Salicylates: [P] Decreased uricosuric effect of probenecid (interaction unlikely with less than 1.5 g of salicylate daily). |
| Quinidine | Substrate of CYP3A4. Inhibits CYP2D6. Renal excretion susceptible to changes in urine pH. Additive effects with other agents that prolong the QTc interval. | Acetazolamide: [P] Decreased renal quinidine excretion due to increased urinary pH; elevated serum quinidine. Amiodarone: [NP] Increased serum quinidine levels; additive prolongation of QTc interval. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of quinidine. Boceprevir: [P] Decreased metabolism of quinidine. Cobicistat: [P] Decreased metabolism of quinidine. Conivaptan: [P] Decreased metabolism of quinidine. Kaolin-pectin: [NE] Decreased gastrointestinal absorption of quinidine. Kinase inhibitors: [P] Decreased metabolism of quinidine with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Rifampin: [P] Increased quinidine metabolism. Thioridazine: [NE] Decreased thioridazine metabolism; additive prolongation of QTc interval. See also Anticoagulants, oral; Antidepressants, tricyclic; Azole antifungals; Barbiturates; Cimetidine; Digitalis glycosides; Macrolides; Phenytoin. |
| Quinolone antibiotics | Susceptible to inhibition of gastrointestinal absorption. Some quinolones (ciprofloxacin, enoxacin) inhibit CYP1A2, while ciprofloxacin also inhibits CYP3A4. | Caffeine: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit caffeine metabolism. Frovatriptan: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit frovatriptan metabolism. Ropinirole: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit ropinirole metabolism. Sucralfate: [HP] Reduced gastrointestinal absorption of ciprofloxacin, norfloxacin, and probably other quinolones. Theophylline: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit theophylline metabolism. Tizanidine: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit tizanidine metabolism. Zolmitriptan: [P] Ciprofloxacin, enoxacin, and, to a lesser extent, norfloxacin inhibit zolmitriptan metabolism. See also Acid-reducing agents; Anticoagulants, oral; Iron. |
| Rifampin | Inducer (strong) of hepatic microsomal drug-metabolizing enzymes and P-glycoprotein. | Corticosteroids: [P] Increased corticosteroid hepatic metabolism; reduced corticosteroid effect. Mexiletine: [NE] Increased mexiletine metabolism; reduced mexiletine effect. Sulfonylurea hypoglycemics: [P] Increased hepatic metabolism of tolbutamide and probably other sulfonylureas metabolized by the liver (including chlorpropamide). Theophylline: [P] Increased theophylline metabolism. See also Anticoagulants, oral; Antidepressants, tricyclic and heterocyclic; Azole antifungals; Beta-adrenoceptor blockers; Calcium channel blockers; Cyclosporine; Digitalis glycosides; Estrogens; HMG-CoA reductase inhibitors; Opioid analgesics; Phenytoin; Quinidine. |
| Salicylates | Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. | Carbonic anhydrase inhibitors: [NE] Increased acetazolamide serum concentrations; increase salicylate toxicity due to decreased blood pH. Corticosteroids: [P] Increased salicylate elimination; possible additive toxic effect on gastric mucosa. Heparin: [NP] Increased bleeding tendency with aspirin, but probably not with other salicylates. Methotrexate: [P] Decreased renal methotrexate clearance; increases methotrexate toxicity (primarily at anticancer doses). Selective serotonin reuptake inhibitors (SSRIs): [P] Increased risk of bleeding due to platelet inhibition. Sulfinpyrazone: [HP] Decreased uricosuric effect of sulfinpyrazone (interaction unlikely with less than 1.5 g of salicylate daily). See also Acid-reducing agents; Anticoagulants, oral; Probenecid. |
| Selective serotonin reuptake inhibitors (SSRIs) | SSRIs can lead to excessive serotonin response when administered with other serotonergic drugs (eg, MAOIs). Some SSRIs inhibit various cytochrome P450s including CYP2D6, CYP1A2, CYP3A4, and CYP2C19. | Codeine: [HP] Reduced analgesic effect due to inhibition of codeine metabolism to morphine by fluoxetine and paroxetine. Theophylline: [P] Decreased metabolism of theophylline by fluvoxamine-induced inhibition of CYP1A2. See also Anticoagulants, oral; Antidepressants, tricyclic and heterocyclic; β-Adrenoceptor blockers; Carbamazepine; Cisapride; Colchicine; Cyclosporine; HMG-CoA reductase inhibitors; Monoamine oxidase inhibitors; Nonsteroidal anti-inflammatory drugs; Phenytoin; Pimozide; Salicylates. |
| Theophylline | Susceptible to induction and inhibition of hepatic metabolism by CYP1A2 and CYP3A4. | Beta-adrenoceptor blockers: [NP] Decreased theophylline bronchodilation especially with noncardioselective β blockers. Smoking: [HP] Increased theophylline metabolism. Tacrine: [NP] Decreased theophylline metabolism. Ticlopidine: [NP] Decreased theophylline metabolism. Zileuton: [NP] Decreased theophylline metabolism. See also Barbiturates; Calcium channel blockers; Carbamazepine; Cimetidine; Lithium; Macrolides; Phenytoin; Quinolones; Rifampin; Selective serotonin reuptake inhibitors. |