| Drug or Drug Group | Properties Promoting Drug Interaction | Clinically Documented Interactions |
|---|---|---|
| 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. | 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. | ||
| Antacids | Antacids may adsorb drugs in gastrointestinal tract, thus reducing absorption. Antacids tend to speed gastric emptying, thus delivering drugs to absorbing sites in the intestine more quickly. Some antacids (eg, magnesium hydroxide with aluminum hydroxide) alkalinize the urine somewhat, thus altering excretion of drugs sensitive to urinary pH. | Atazanavir: [NP] Decreased absorption of atazanavir (requires acid for absorption). |
| Digoxin: [NP] Decreased gastrointestinal absorption of digoxin. | ||
| Indinavir: [NP] Decreased absorption of indinavir (requires acid for absorption). | ||
| Iron: [P] Decreased gastrointestinal absorption of iron with calcium-containing antacids. | ||
| Itraconazole: [P] Reduced gastrointestinal absorption of itraconazole due to increased pH (itraconazole requires acid for absorption). | ||
| Ketoconazole: [P] Reduced gastrointestinal absorption of ketoconazole due to increased pH (ketoconazole requires acid for absorption). | ||
| Quinolones: [HP] Decreased gastrointestinal absorption of ciprofloxacin, norfloxacin, enoxacin (and probably other quinolones). | ||
| Salicylates: [P] Increased renal clearance of salicylates due to increased urine pH; occurs only with large doses of salicylates. | ||
| Sodium polystyrene sulfonate: [NE] Binds antacid cation in gut, resulting in metabolic alkalosis. | ||
| Tetracyclines: [HP] Decreased gastrointestinal absorption of tetracyclines. | ||
| Thyroxine: [NP] Reduced gastrointestinal absorption of thyroxine. | ||
| Anticoagulants, oral | Metabolism inducible. Susceptible to inhibition of metabolism by CYP2C9. 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. | ||
| Amiodarone: [P] Inhibited anticoagulant metabolism. | ||
| Anabolic steroids: [P] Altered clotting factor disposition? | ||
| Chloramphenicol: [NE] Decreased dicumarol metabolism (probably also warfarin). | ||
| Cimetidine: [HP] Decreased warfarin metabolism. | ||
| Clofibrate: [P] Mechanism not established. | ||
| Clopidogrel: [NP] Decreased warfarin metabolism and inhibits platelet function. | ||
| Danazol: [NE] Impaired synthesis of clotting factors? | ||
| Dextrothyroxine: [P] Enhanced clotting factor catabolism? | ||
| Disulfiram: [P] Decreased warfarin metabolism. | ||
| Erythromycin: [NP] Probably inhibits anticoagulant metabolism. | ||
| Fluconazole: [P] Decreased warfarin metabolism. | ||
| Gemfibrozil: [NE] Mechanism not established. | ||
| Lovastatin: [NP] Decreased warfarin metabolism. | ||
| Metronidazole: [P] Decreased warfarin metabolism. | ||
| Miconazole: [NE] Decreased warfarin metabolism. | ||
| Nonsteroidal anti-inflammatory drugs: [P] Inhibition of platelet function, gastric erosions; some agents increase hypoprothrombinemic response (unlikely with diclofenac, ibuprofen, or naproxen). | ||
| Propafenone: [NE] Probably decreases anticoagulant metabolism. | ||
| Quinidine: [NP] Additive hypoprothrombinemia. | ||
| 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. | ||
| Thyroid hormones: [P] Enhanced clotting factor catabolism. | ||
| Trimethoprim-sulfamethoxazole: [P] Inhibited warfarin metabolism; displaces from protein binding. | ||
| Voriconazole: [NP] Decreased warfarin metabolism. | ||
| See also Alcohol; Allopurinol. | ||
| Drugs that may decrease anticoagulant effect: | ||
| Aminoglutethimide: [P] Enzyme induction. | ||
| Barbiturates: [P] Enzyme induction. | ||
| Carbamazepine: [P] Enzyme induction. | ||
| Cholestyramine: [P] Reduced absorption of anticoagulant. | ||
| Glutethimide: [P] Enzyme induction. | ||
| Nafcillin: [NE] Enzyme induction. | ||
| Phenytoin: [NE] Enzyme induction; anticoagulant effect may increase transiently at start of phenytoin therapy due to protein-binding displacement. | ||
| Primidone: [P] Enzyme induction. | ||
| Rifabutin: [P] Enzyme induction. | ||
| Rifampin: [P] Enzyme induction. | ||
| St. John’s wort: [NE] Enzyme induction. | ||
| Effects of anticoagulants on other drugs: | ||
| Hypoglycemics, oral: [P] Dicumarol inhibits hepatic metabolism of tolbutamide and chlorpropamide. | ||
| Phenytoin: [P] Dicumarol inhibits metabolism of phenytoin. | ||
| Antidepressants, tricyclic and heterocyclic | Inhibition of amine uptake into postganglionic adrenergic neuron. Antimuscarinic effects may be additive with other antimuscarinic drugs. Metabolism inducible. Susceptible to inhibition of metabolism by CYP2D6 and other CYP450 enzymes. | Barbiturates: [P] Increased antidepressant metabolism. |
| Bupropion: [NE] Decreased antidepressant metabolism. | ||
| Carbamazepine: [NE] Enhanced metabolism of antidepressants. | ||
| Cimetidine: [P] Decreased antidepressant metabolism. | ||
| Clonidine: [P] Decreased clonidine antihypertensive effect. | ||
| Guanadrel: [P] Decreased uptake of guanadrel into sites of action. | ||
| Guanethidine: [P] Decreased uptake of guanethidine into sites of action. | ||
| Monoamine oxidase inhibitors: [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: [NE] Decreased antidepressant metabolism. | ||
| 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. | ||
| Azole antifungals | Inhibition of CYP3A4 (itraconazole = ketoconazole > posaconazole > voriconazole > fluconazole). Inhibition of CYP2C9 (fluconazole, voriconazole). Susceptible to enzyme inducers (itraconazole, ketoconazole, voriconazole). Gastrointestinal absorption pH-dependent (itraconazole, ketoconazole). Inhibition of P-glycoprotein (itraconazole, ketoconazole, posaconazole). | Barbiturates: [P] Increased metabolism of itraconazole, ketoconazole, voriconazole. |
| Calcium channel blockers: [P] Decreased calcium channel blocker metabolism. | ||
| Carbamazepine: [P] Decreased carbamazepine metabolism. | ||
| Cisapride: [NP] Decreased metabolism of cisapride; possible ventricular arrhythmias. | ||
| Cyclosporine: [P] Decreased metabolism of cyclosporine. | ||
| Digoxin: [NE] Increased plasma concentrations of digoxin with itraconazole, posaconazole, and ketoconazole. | ||
| H2-receptor antagonists: [NE] Decreased absorption of itraconazole and ketoconazole. | ||
| HMG CoA reductase inhibitors: Decreased metabolism of lovastatin, simvastatin, and, to a lesser extent, atorvastatin. | ||
| Phenytoin: [P] Decreased metabolism of phenytoin with fluconazole and probably voriconazole. | ||
| Pimozide: [NE] Decreased pimozide metabolism. | ||
| Proton pump inhibitors: [P] Decreased absorption of itraconazole and ketoconazole. | ||
| Rifampin: [P] Increased metabolism of itraconazole, ketoconazole, and voriconazole. | ||
| See also Antacids; Anticoagulants, oral. | ||
| Barbiturates | Induction of hepatic microsomal drug metabolizing enzymes. Additive central nervous system depression with other central nervous system depressants. | 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. | ||
| Delavirdine: [P] Increased delavirdine metabolism. | ||
| Doxycycline: [P] Increased doxycycline metabolism. | ||
| Estrogens: [P] Increased estrogen metabolism. | ||
| Methadone: [NE] Increased methadone metabolism. | ||
| Phenothiazine: [P] Increased phenothiazine metabolism. | ||
| Protease inhibitors: [NE] Increased protease inhibitor metabolism. | ||
| Quinidine: [P] Increased quinidine metabolism. | ||
| Sirolimus: [NE] Increased sirolimus metabolism. | ||
| Tacrolimus: [NE] Increased tacrolimus metabolism. | ||
| Theophylline: [NE] Increased theophylline metabolism; reduced theophylline effect. | ||
| Valproic acid: [P] Decreased phenobarbital metabolism. | ||
| See also Anticoagulants, oral; Antidepressants, tricyclic. | ||
| Beta-adrenoceptor blockers | Beta-blockade (especially with nonselective agents such as propranolol) alters response to sympathomimetics with β-agonist activity (eg, epinephrine). β Blockers that undergo extensive first-pass metabolism may be affected by drugs capable of altering this process. β Blockers may reduce hepatic blood flow. | Drugs that may increase β-blocker effect: |
| 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. | ||
| Selective serotonin reuptake inhibitors (SSRIs): [P] Fluoxetine and paroxetine inhibit CYP2D6 and increase concentrations of timolol, propranolol, metoprolol, carvedilol, and labetalol. | ||
| Drugs that may decrease β-blocker effect: | ||
| Enzyme inducers: [P] Barbiturates, phenytoin, and rifampin may enhance β-blocker metabolism; other enzyme inducers may produce similar effects. | ||
| Nonsteroidal anti-inflammatory drugs: [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 while patient is taking propranolol. | ||
| 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 nonselective β blockers. | ||
| See also 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 (but not nifedipine) inhibit hepatic drug-metabolizing enzymes. Metabolism of diltiazem, nifedipine, verapamil, and probably other calcium channel blockers subject to induction and inhibition. | Carbamazepine: [P] Decreased carbamazepine metabolism with diltiazem and verapamil; possible increase in calcium channel blocker metabolism. |
| Cimetidine: [NP] Decreased metabolism of calcium channel blockers. | ||
| Cyclosporine: [P] Decreased cyclosporine metabolism with diltiazem, nicardipine, verapamil. | ||
| Phenytoin: [NE] Increased metabolism of calcium channel blockers. | ||
| Rifampin: [P] Increased metabolism of calcium channel blockers. | ||
| Sirolimus: [P] Decreased sirolimus metabolism with diltiazem, nicardipine, verapamil. | ||
| Tacrolimus: [P] Decreased tacrolimus metabolism with diltiazem, nicardipine, verapamil. | ||
| See also Azole antifungals; Barbiturates; Theophyllin; Digitalis glycosides. | ||
| Carbamazepine | Induction of hepatic microsomal drug-metabolizing enzymes. Susceptible to inhibition of metabolism, primarily by CYP3A4. | Cimetidine: [P] Decreased carbamazepine metabolism. |
| Clarithromycin: [P] Decreased carbamazepine metabolism. | ||
| Corticosteroids: [P] Increased corticosteroid metabolism. | ||
| Cyclosporine: [P] Increased cyclosporine metabolism. | ||
| Danazol: [P] Decreased carbamazepine metabolism. | ||
| Doxycycline: [P] Increased doxycycline metabolism. | ||
| Erythromycin: [NE] Decreased carbamazepine metabolism. | ||
| Fluvoxamine: [NE] Decreased carbamazepine metabolism. | ||
| Estrogens: [P] Increased estrogen metabolism. | ||
| Haloperidol: [P] Increased haloperidol metabolism. | ||
| Isoniazid: [P] Decreased carbamazepine metabolism. | ||
| Nefazodone: [NE] Decreased carbamazepine metabolism. | ||
| Propoxyphene: [HP] Decreased carbamazepine metabolism. | ||
| 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. | ||
| Chloramphenicol | Inhibits hepatic drug-metabolizing enzymes. | Phenytoin: [P] Decreased phenytoin metabolism. |
| Sulfonylurea hypoglycemics: [P] Decreased sulfonylurea metabolism. | ||
| See also Anticoagulants, oral. | ||
| Cimetidine | Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not.) May inhibit the renal tubular secretion of weak bases. | Atazanavir: [NP] Decreased absorption of atazanavir (requires acid for absorption; other H2 blockers and proton pump inhibitors would be expected to have the same effect). |
| Benzodiazepines: [P] Decreased metabolism of alprazolam, chlordiazepoxide, diazepam, halazepam, prazepam, and clorazepate but not oxazepam, lorazepam, or temazepam. | ||
| Carmustine: [NE] Increased bone marrow suppression. | ||
| Indinavir: [NP] Decreased absorption of indinavir (requires acid for absorption; other H2 blockers and proton pump inhibitors would be expected to have the same effect). | ||
| Ketoconazole: [NE] Decreased absorption of ketoconazole (requires acid for absorption; other H2 blockers and proton pump inhibitors would be expected to have the same effect). | ||
| Itraconazole: [NE] Decreased absorption of itraconazole (requires acid for absorption; other H2-receptor antagonists and proton pump inhibitors would be expected to have the same effect). | ||
| Lidocaine: [P] Decreased metabolism of lidocaine; increased serum lidocaine. | ||
| Phenytoin: [NE] Decreased phenytoin metabolism; increased serum phenytoin. | ||
| Procainamide: [P] Decreased renal excretion of procainamide; Increased serum procainamide levels. Similar effect with ranitidine but smaller. | ||
| Quinidine: [P] Decreased metabolism of quinidine; Increased serum quinidine levels. | ||
| Theophylline: [P] Decreased theophylline metabolism; Increased plasma theophylline. | ||
| See also Anticoagulants, oral; Antidepressants, tricyclic; Beta-adrenoceptor blockers; Calcium channel blockers; Carbamazepine. | ||
| Cisapride | Susceptible to inhibition of metabolism by CYP3A4 inhibitors. High cisapride serum concentrations can result in ventricular arrhythmias. | Clarithromycin: [NP] Decreased metabolism of cisapride; possible ventricular arrhythmia. |
| Cyclosporine: [NE] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Erythromycin: [NP] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Fluconazole: [NE] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Itraconazole: [NP] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Ketoconazole: [NP] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Nefazodone: [NP] Possibly decreased metabolism of cisapride by CYP3A4; possible ventricular arrhythmia. | ||
| Ritonavir: [NE] Decreased metabolism of cisapride; possible ventricular arrhythmia. | ||
| Selective serotonin reuptake inhibitors (SSRIs): [NP] Fluvoxamine inhibits CYP3A4 and probably decreases cisapride metabolism; possible ventricular arrhythmia. | ||
| Cyclosporine | Metabolism inducible. Susceptible to inhibition of metabolism by CYP3A4. (Tacrolimus and sirolimus appear to have similar interactions.) | Aminoglycosides: [NE] Possible additive nephrotoxicity. |
| Amphotericin B: [NE] Possible additive nephrotoxicity. | ||
| Amprenavir: [P] Increased cyclosporine metabolism. | ||
| Androgens: [NE] Increased serum cyclosporine. | ||
| Barbiturates: [P] Increased cyclosporine metabolism. | ||
| Carbamazepine: [P] Increased cyclosporine metabolism. | ||
| Clarithromycin: [P] Decreased cyclosporine metabolism. | ||
| Erythromycin: [NE] Decreased cyclosporine metabolism. | ||
| Lovastatin: [NE] Myopathy and rhabdomyolysis noted in patients taking lova-statin and cyclosporine. | ||
| Nefazodone: [P] Decreased cyclosporine metabolism. | ||
| Phenytoin: [NE] Increased cyclosporine metabolism. | ||
| Pimozide: [NE] Decreased pimozide metabolism. | ||
| Quinupristin: [P] Increased cyclosporine metabolism. | ||
| Rifampin: [P] Increased cyclosporine metabolism. | ||
| Ritonavir: [P] Decreased cyclosporine metabolism. | ||
| Simvastatin: [NE] Myopathy and rhabdomyolysis noted in patients taking sim-vastatin and cyclosporine. | ||
| St. John’s wort: [NE] Increased cyclosporine metabolism. | ||
| See also Azole antifungals; Barbiturates; Calcium channel blockers. | ||
| Digitalis glycosides | Digoxin susceptible to alteration of gastrointestinal absorption. Digitalis toxicity may be increased by drug-induced electrolyte imbalance (eg, hypokalemia). Digitoxin metabolism inducible. Renal and nonrenal excretion of digoxin susceptible to inhibition. | Drugs that may increase digitalis effect: |
| Amiodarone: [P] Increased plasma digoxin concentrations. | ||
| Clarithromycin: [NP] Increased plasma concentration of digoxin. | ||
| Diltiazem: [P] Increased plasma digoxin and additive AV conduction effects. | ||
| Erythromycin: [NE] Increased plasma concentration of digoxin. | ||
| Potassium-depleting drugs: [P] Increases likelihood of digitalis toxicity. | ||
| Propafenone: [P] Increases plasma digoxin levels. | ||
| Quinidine: [HP] Increased digoxin plasma concentrations; displaces digoxin from tissue binding sites. | ||
| Spironolactone: [NE] Decreased renal digoxin excretion and interfers with some serum digoxin assays. | ||
| Verapamil: [P] Increased plasma digoxin levels and additive AV conduction effects. | ||
| See also Azole antifungals. | ||
| Drugs that may decrease digitalis effect: | ||
| Kaolin-pectin: [P] Decreased gastrointestinal digoxin absorption. | ||
| Rifampin: [NE] Increased metabolism of digitoxin and elimination digoxin. | ||
| Sulfasalazine: [NE] Decreased gastrointestinal digoxin absorption. | ||
| See also Antacids; Bile acid–binding resins. | ||
| Disulfiram | Inhibits hepatic microsomal drug-metabolizing enzymes. 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 | Metabolism inducible. 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. |
| Corticosteroids: [P] Decreased metabolism of corticosteroids leading to increased corticosteroid effect. | ||
| Griseofulvin: [NE] Possible inhibition of oral contraceptive efficacy; mechanism unknown. | ||
| Phenytoin: [NP] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. | ||
| Primidone: [NP] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. | ||
| Rifabutin: [NP] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. | ||
| Rifampin: [NP] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. | ||
| St. John’s wort: [NE] Increased estrogen metabolism; possible reduction in oral contraceptive efficacy. | ||
| See also Barbiturates; Carbamazepine. | ||
| HMG-CoA reductase inhibitors | Lovastatin, simvastatin, and, to a lesser extent, atorvastatin are susceptible to CYP3A4 inhibitors; lovastatin, simvastatin, and, to a lesser extent, atorvastatin are susceptible to CYP3A4 inducers; increased risk of additive myopathy risk with other drugs that can cause myopathy. | Amiodarone: [NP] Decreased statin metabolism. |
| Atazanavir: [NP] Decreased statin metabolism. | ||
| Carbamazepine: [P] Decreased statin metabolism. | ||
| Clarithromycin: [P] Decreased statin metabolism. | ||
| Clofibrate: [NP] Increased risk of myopathy. | ||
| Cyclosporine: [P] Decreased statin metabolism. | ||
| Diltiazem: [NE] Decreased statin metabolism. | ||
| Erythromycin: [P] Decreased statin metabolism. | ||
| Gemfibrozil: [NP] Increased plasma lovastatin and simvastatin. | ||
| Indinavir: [NE] Decreased statin metabolism. | ||
| Nefazodone: [NE] Decreased statin metabolism. | ||
| Rifampin: [P] Increased statin metabolism. | ||
| Ritonavir: [NE] Decreased statin metabolism. | ||
| St. John’s wort: [NP] Increased statin metabolism. | ||
| Verapamil: [NE] Decreased statin metabolism. | ||
| See also Azole antifungals; Cyclosporine. | ||
| Iron | Binds with drugs in gastrointestinal tract, reducing absorption. | Methyldopa: [NE] Decreased methyldopa absorption. |
| Mycophenolate: [P] Decreased absorption of mycophenolate. | ||
| Quinolones: [P] Decreased absorption of ciprofloxacin. | ||
| 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. Anti-parkinsonism effect of levodopa susceptible to inhibition by other drugs. | Clonidine: [NE] Inhibited antiparkinsonism effect. |
| Monoamine oxidase inhibitors: [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). | ||
| See also Antimuscarinics. | ||
| 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: [NE] Probably reduce renal clearance of lithium; increase lithium effect. |
| Angiotensin II receptor blockers: [NE] Probably 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 (SSRIs given): [NE] Reduced renal lithium excretion (except sulindac and salicylates). | ||
| Theophylline: [P] Increased renal excretion of lithium; reduced lithium effect. | ||
| 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: [NE] 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. | ||
| Narcotic analgesics: [NP] Some patients develop hypertension, rigidity, excitation; meperidine may be more likely to interact than morphine. | ||
| Nefazodone: [NE] Possible serotonin syndrome; 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. | ||
| 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: [NE] Possible serotonin syndrome; avoid concurrent use. | ||
| Venlafaxine: [NE] 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. Most NSAIDs are highly bound to plasma proteins. | ACE inhibitors: [P] Decreased antihypertensive response. |
| Angiotensin II receptor blockers: [P] Decreased antihypertensive response. | ||
| Furosemide: [P] Decreased diuretic, natriuretic, and antihypertensive response to furosemide. | ||
| Hydralazine: [NE] Decreased antihypertensive response to hydralazine. | ||
| Methotrexate: [NE] Possibly increased methotrexate toxicity (especially with anticancer doses of methotrexate). | ||
| Selective serotonin reuptake inhibitors (SSRIs): Increased risk of bleeding due to platelet inhibition. | ||
| Triamterene: [NE] Decreased renal function noted with triamterene plus indomethacin in both healthy subjects and patients. | ||
| See also Anticoagulants, oral; Beta-adrenoceptor blockers; Lithium. | ||
| 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. | ||
| Methadone: [P] Decreased serum methadone levels; withdrawal symptoms. | ||
| Mexiletine: [NE] Decreased serum mexiletine levels. | ||
| Quinidine: [P] Decreased serum quinidine levels. | ||
| Theophylline: [NE] Decreased serum theophylline levels. | ||
| Verapamil: [NE] Decreased serum verapamil levels. | ||
| See also Calcium channel blockers, Cyclosporine, Estrogens. | ||
| Drugs that inhibit phenytoin metabolism: | ||
| Amiodarone: [P] Increased serum phenytoin; possible reduction in serum amiodarone. | ||
| Capecitabine: [NE] Increased serum phenytoin. | ||
| Chloramphenicol: [P] Increased serum phenytoin. | ||
| Felbamate: [P] Increased serum phenytoin. | ||
| Fluorouracil: [NE] Increased serum phenytoin. | ||
| Fluvoxamine: [NE] Increased serum phenytoin. | ||
| Isoniazid: [NP] Increased serum phenytoin; problem primarily with slow acetylators of isoniazid. | ||
| Metronidazole: [NP] Increased serum phenytoin. | ||
| Ticlopidine: [NP] Increased serum phenytoin. | ||
| See also Azole antifungals, Cimetidine; Disulfiram. | ||
| Drugs that enhance phenytoin metabolism: | ||
| Carbamazepine: [P] Decreased serum phenytoin levels. | ||
| Rifampin: [P] Decreased serum phenytoin levels. | ||
| Pimozide | Susceptible to CYP3A4 inhibitors; may exhibit additive effects with other agents that prolong QTc interval. | Clarithromycin: [NE] Decreased pimozide metabolism. |
| Erythromycin: [NE] Decreased pimozide metabolism. | ||
| Nefazodone: [NE] Decreased pimozide metabolism. | ||
| See also Azole antifungals; Cyclosporine. | ||
| Potassium-sparing diuretics (amiloride, spironolactone, triamterene) | Additive effects with other agents increasing serum potassium concentration. May alter renal excretion of substances other than potassium (eg, digoxin, hydrogen ions). | ACE inhibitors: [NP] Additive hyperkalemic effect. |
| Angiotensin II receptor blockers: [NP] Additive hyperkalemic effect. | ||
| Eplerenone: [P] Additive hyperkalemic effect. | ||
| Potassium supplements: [P] Additive hyperkalemic effect; especially a problem in presence of renal impairment. | ||
| See also Digitalis glycosides; 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. | ||
| 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 | Metabolism inducible. 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: [NE] Increased serum quinidine levels; mechanism not established. | ||
| Kaolin-pectin: [NE] Decreased gastrointestinal absorption of quinidine. | ||
| Rifampin: [P] Increased hepatic quinidine metabolism. | ||
| Thioridazine: [NE] Decreased thioridazine metabolism; additive prolongation of QTc interval. | ||
| See also Anticoagulants, oral; Antidepressants, tricyclic; Barbiturates; Cimetidine; Digitalis glycosides; Phenytoin. | ||
| Quinolone antibiotics | Susceptible to inhibition of gastrointestinal absorption. Some quinolones inhibit CYP1A2. | Caffeine: [P] Ciprofloxacin, enoxacin, pipedemic acid, and to a lesser extent, norfloxacin, inhibit caffeine 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; gatifloxacin, levofloxacin, lomefloxacin, ofloxacin, and sparfloxacin appear to have little effect. | ||
| See also Antacids; Anticoagulants, oral; Iron. | ||
| Rifampin | Inducer (strong) of hepatic microsomal drug-metabolizing enzymes. | 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; reduced theophylline effect. | ||
| See also Anticoagulants, oral; Azole antifungals; Beta-adrenoceptor blockers; Calcium channel blockers; Cyclosporine; Digitalis glycosides; Estrogens. | ||
| 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: [NE] Increased bleeding tendency with aspirin, but probably not with other salicylates. | ||
| Methotrexate: [P] Decreased renal methotrexate clearance; increases methotrexate toxicity (primarily at anticancer doses). | ||
| Sulfinpyrazone: [HP] Decreased uricosuric effect of sulfinpyrazone (interaction unlikely with less than 1.5 g of salicylate daily). | ||
| See also Antacids; Anticoagulants, oral; Probenecid. | ||
| Theophylline | Susceptible to inhibition of hepatic metabolism by CYP1A2. Metabolism inducible. | Benzodiazepines: [NE] Inhibition of benzodiazepine sedation. |
| β-Adrenoceptor blockers: [NP] Decreased theophylline bronchodilation. | ||
| Diltiazem: [P] Decreased theophylline metabolism. | ||
| Clarithromycin: [NE] Decreased theophylline metabolism. | ||
| Erythromycin: [P] Decreased theophylline metabolism. | ||
| Fluvoxamine: [P] Decreased theophylline metabolism. | ||
| Smoking: [HP] Increased theophylline metabolism. | ||
| Tacrine: [P] Decreased theophylline metabolism. | ||
| Ticlopidine: [NE] Decreased theophylline metabolism. | ||
| Verapamil: [P] Decreased theophylline metabolism. | ||
| Zileuton: [P] Decreased theophylline metabolism. | ||
| See also Barbiturates; Carbamazepine; Cimetidine; Lithium; Phenytoin; Quinolones; Rifampin. |
HP, Highly predictable. Interaction occurs in almost all patients receiving the interacting combination; P, Predictable. Interaction occurs in most patients receiving the combination; NP, Not predictable. Interaction occurs only in some patients receiving the combination; NE, Not established. Insufficient data available on which to base estimate of predictability.