|
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  -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 -agonist activity (eg,
epinephrine). Blockers that undergo extensive
first-pass metabolism may be affected by drugs capable of altering
this process. Blockers may reduce hepatic blood
flow.
|
Drugs that
may increase -blocker effect:
|
|
Cimetidine: [P]
Decreased metabolism of 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 -blocker effect:
|
|
Enzyme
inducers: [P] Barbiturates, phenytoin, and rifampin may enhance
-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 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 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.
|
|
-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.
|