When 2 or more drugs are administered to the same patient, the pharmacokinetic and pharmacodynamic properties of each agent may be modified by their interaction. Drugs may interact by a number of mechanisms classified on the basis of pharmaceutics, pharmacokinetics, pharmacodynamics, or a combination thereof. These interactions may result in unpredictable clinical effects or toxicologic responses.
Pharmaceutic interactions include those resulting in drug inactivation when compounds are mixed together physically before patient administration, as with the use of syringes, infusion tubing, dialysate solutions, or parenteral fluid preparations.
Pharmacokinetic interactions can occur when the disposition characteristics of 1 compound (absorption, distribution, metabolism, excretion, or a combination thereof) are influenced by those of another.
Drugs may interact pharmacodynamically and compete for the same receptor or physiologic system, thus altering a patient's response to drug therapy. | INTERACTING AGENT | ADVERSE EFFECT |
|---|---|
| ACETAMINOPHEN | |
| Alcohol | Hepatotoxicity |
| Oral anticoagulants | ↑ Anticoagulation |
| Probenecid | ↑ Acetaminophen toxicity |
| Zidovudine | Granulocytopenia |
| ACYCLOVIR | |
| Narcotics | ↑ Narcotic toxicity? |
| Zidovudine | Lethargy |
| ALCOHOL | |
| Antidepressants (tricyclic) | ↑ Toxicity |
| Barbiturates | ↑ CNS depression (acute) |
| Benzodiazepines | ↑ CNS depression |
| Cephalosporins (not all) | Disulfiram effect |
| Chloral hydrate | ↑ CNS depression |
| Doxycycline | ↓ Antibiotic effect |
| Isoniazid | ↑ Hepatotoxicity |
| Metronidazole | Disulfiram effect |
| Phenothiazines | Impaired coordination |
| Phenytoin | ↑ Phenytoin toxicity |
| ALLOPURINOL | |
| Aluminum hydroxide | ↓ Allopurinol absorption |
| Ampicillin | Rash |
| Anticoagulants (oral) | ↑ Anticoagulant effect |
| Azathioprine | ↑ Azathioprine toxicity |
| Captopril | ↑ Cutaneous hypersensitivity |
| Cyclophosphamide | ↑ Cyclophosphamide toxicity |
| Theophylline | ↑ Theophylline toxicity |
| Thiazide diuretics | ↑ Allopurinol toxicity |
| AMINOGLYCOSIDE ANTIBIOTICS | |
| Amphotericin B | ↑ Nephrotoxicity |
| Bumetanide | ↑ Ototoxicity |
| Cisplatin | ↑ Nephrotoxicity |
| Cyclosporine | ↑ Nephrotoxicity |
| Furosemide | ↑ Nephrotoxicity and ototoxicity |
| Magnesium | ↑ Neuromuscular blockade |
| Neuromuscular blocking agents | ↑ Blockade |
| Vancomycin | ↑ Nephrotoxicity? |
| ANTACIDS | |
| β-Adrenergic blockers | ↓ Absorption |
| Captopril | ↓ Absorption |
| Cimetidine | ↓ Absorption |
| Corticosteroids | ↓ Absorption |
| Digoxin | ↓ Absorption |
| Iron | ↓ Absorption |
| Isoniazid | ↓ Absorption |
| Ketoconazole | ↓ Absorption |
| Nonsteroidal anti-inflammatory agents | ↓ Absorption |
| Phenytoin | ↓ Absorption |
| Salicylates | ↓ Absorption |
| Tetracycline | ↓ Absorption |
| Theophylline | ↑ Toxicity |
| ASPIRIN | |
| Anticoagulants (oral) | ↑ Bleeding |
| Captopril | ↓ Antihypertensive effect |
| BARBITURATES | |
| Anticoagulants (oral) | ↓ Anticoagulation |
| β-Adrenergic blockers | ↓ β Blockade |
| Carbamazepine | ↑ Production of carbamazepine epoxide |
| Chloramphenicol | ↑ Barbiturate toxicity |
| Contraceptives (oral) | ↓ Contraception |
| Corticosteroids | ↓ Steroid effect |
| Influenza vaccine (viral) | ↑ Barbiturate toxicity |
| Rifampin | ↓ Barbiturate effect |
| Theophylline | ↓ Theophylline effect |
| Valproate | ↑ Barbiturate toxicity |
| BLEOMYCIN | |
| Oxygen | ↑ Pulmonary toxicity |
| CAPTOPRIL | |
| Allopurinol | ↑ Cutaneous hypersensitivity |
| Aspirin | ↓ Antihypertensive effect |
| Cimetidine | Neuropathy |
| Nonsteroidal anti-inflammatory agents | ↓ Antihypertensive effect |
| Potassium | Hyperkalemia |
| Spironolactone | Hyperkalemia |
| CARBAMAZEPINE | |
| Anticoagulants (oral) | ↓ Anticoagulation |
| Antidepressants (tricyclic) | ↑ Toxicity (both drugs) |
| Cimetidine | ↑ Carbamazepine toxicity |
| Contraceptives (oral) | ↓ Contraception |
| Corticosteroids | ↓ Steroid effect |
| Cyclosporine | ↓ Cyclosporine effect |
| Erythromycins | ↑ Carbamazepine toxicity |
| Influenza vaccine (viral) | ↑ Carbamazepine toxicity |
| Isoniazid | ↑ Toxicity (both drugs) |
| Phenytoin | ↓ Carbamazepine effect |
| Theophylline | ↓ Theophylline effect |
| Valproate | ↓ Valproate effect |
| CIMETIDINE | |
| Alcohol | ↑ Alcohol effect |
| Antacids | ↓ Cimetidine effect |
| Anticoagulants (oral) | ↑ Anticoagulation |
| Antidepressants (tricyclic) | ↑ Antidepressant toxicity |
| Benzodiazepines | ↑ Benzodiazepine toxicity |
| β-Adrenergic blocking agents | ↑ β-Blockade toxicity |
| Captopril | Neuropathy |
| Carbamazepine | ↑ Carbamazepine toxicity |
| Digoxin | ↑ Digoxin toxicity |
| Ketoconazole | ↓ Ketoconazole absorption |
| Metoclopramide | ↓ Cimetidine effect |
| Phenytoin | ↑ Phenytoin toxicity |
| Theophylline | ↑ Theophylline toxicity |
| CONTRACEPTIVES (ORAL) | |
| Anticoagulants (oral) | ↓ Anticoagulation |
| Antidepressants (tricyclic) | ↑ Antidepressant toxicity |
| Barbiturates | ↓ Contraception |
| Carbamazepine | ↓ Contraception |
| Griseofulvin | ↓ Contraception |
| Penicillins (ampicillin, oxacillin) | ↓ Contraception? |
| Phenytoin | ↓ Contraception |
| Rifampin | ↓ Contraception |
| Theophylline | ↑ Theophylline toxicity |
| CYCLOSPORINE | |
| Alkylating agents | ↑ Nephrotoxicity |
| Aminoglycosides | ↑ Nephrotoxicity |
| Amphotericin B | ↑ Nephrotoxicity |
| Carbamazepine | ↓ Cyclosporine effect |
| Erythromycins | ↑ Cyclosporine toxicity |
| Furosemide | Gout |
| Ketoconazole | ↑ Nephrotoxicity |
| Metoclopramide | ↑ Cyclosporine toxicity |
| Nafcillin | ↓ Cyclosporine effect |
| Phenytoin | ↓ Cyclosporine effect |
| Rifampin | ↓ Cyclosporine effect |
| DIGOXIN | |
| Antacids | ↓ Absorption |
| Anticholinergics | ↑ Digoxin toxicity |
| Cholestyramine | ↓ Absorption |
| Cimetidine | ↑ Digoxin toxicity |
| Diuretics (hypokalemia) | ↑ Digoxin toxicity |
| Phenytoin | ↓ Digoxin effect |
| Quinidine | ↑ Digoxin toxicity |
| Verapamil | ↑ Digoxin toxicity |
| ERYTHROMYCINS | |
| Anticoagulants (oral) | ↑ Anticoagulation |
| Astemizole (Hismanal) | ↑ Astemizole toxicity: arrhythmias |
| Carbamazepine | ↑ Carbamazepine toxicity |
| Cyclosporine | ↑ Cyclosporine toxicity |
| Phenytoin | ↓ Phenytoin effect |
| Terfenadine (Seldane) | ↑ Terfenadine toxicity: arrhythmias |
| Theophylline | ↑ Theophylline toxicity |
| FLUOROQUINOLONES | |
| Antacids | ↓ Antibiotic effect |
| Theophylline | ↑ Theophylline toxicity |
| GRISEOFULVIN | |
| Anticoagulants (oral) | ↓ Anticoagulants |
| Contraceptive (oral) | ↓ Contraceptive |
| ISONIAZID | |
| Alcohol | Hepatitis |
| Antacids | ↓ Isoniazid absorption |
| Carbamazepine | ↑ Toxicity (both) |
| Ketoconazole | ↓ Ketoconazole effect |
| Phenytoin | ↑ Phenytoin toxicity |
| Rifampin | ↑ Hepatotoxicity |
| Valproate | ↑ Hepatic and CNS toxicity |
| KETOCONAZOLE | |
| Antacids | ↓ Absorption |
| Anticoagulants (oral) | ↑ Anticoagulation |
| Cimetidine | ↓ Ketoconazole effect |
| Cyclosporine | ↑ Nephrotoxicity |
| Isoniazid | ↓ Ketoconazole effect |
| Phenytoin | Altered metabolism of both drugs |
| Rifampin | ↑ Effects of both drugs |
| METHOTREXATE | |
| Blood transfusion | ↑ Toxicity |
| Cisplatin | ↑ Methotrexate toxicity |
| Etretinate | ↑ Hepatotoxicity |
| Nonsteroidal anti-inflammatory drugs | ↑ Methotrexate toxicity |
| Trimethoprim/sulfamethoxazole | Megaloblastic anemia |
| METOCLOPRAMIDE | |
| Carbamazepine | Neurotoxicity |
| Cimetidine | ↓ Cimetidine effect |
| Cyclosporine | ↑ Cyclosporine toxicity |
| Digoxin | ↓ Absorption |
| Narcotics | ↑ Sedation |
| NIFEDIPINE | |
| β-Adrenergic blockers | Heart failure, atrioventricular block |
| Cyclosporine | ↑ Gingival hyperplasia |
| Phenytoin | ↑ Phenytoin toxicity |
| Prazosin | Hypotension |
| Quinidine | ↓ Quinidine effect |
| PHENYTOIN | |
| Alcohol | ↑ Toxicity (acute) |
| Antacids | ↓ Phenytoin effect |
| Anticoagulants (oral) | ↓ Phenytoin toxicity, ↑↓ anticoagulation |
| Antidepressants (tricyclic) | ↑ Phenytoin toxicity |
| Carbamazepine | ↓ Carbamazepine effect |
| Chloramphenicol | ↑ Toxicity (both drugs) |
| Cimetidine | ↑ Phenytoin toxicity |
| Contraceptives (oral and implant) | ↓ Contraception |
| Corticosteroids | ↓ Corticosteroid effect |
| Cyclosporine | ↓ Cyclosporine effect |
| Digoxin | ↓ Digoxin effect |
| Dopamine | Hypotension |
| Folic acid | ↓ Phenytoin effect |
| Isoniazid | ↑ Phenytoin toxicity |
| Miconazole | ↓ Phenytoin effect |
| Neuromuscular blocking agents | ↓ Blockade |
| Nifedipine | ↑ Phenytoin toxicity |
| Quinidine | ↓ Quinidine effect |
| Rifampin | ↓ Phenytoin effect |
| Theophylline | ↓ Effects (both drugs) |
| Valproate | ↑ Phenytoin toxicity |
| QUINIDINE | |
| Amiodarone | ↑ Quinidine toxicity |
| Anticoagulants (oral) | ↑ Anticoagulation |
| Barbiturates | ↓ Quinidine effect |
| Cimetidine | ↑ Quinidine toxicity |
| Digoxin | ↑ Digoxin toxicity |
| Metoclopramide | ↓ Quinidine effect |
| Phenytoin | ↓ Quinidine effect |
| Procainamide | ↑ Procainamide toxicity |
| Rifampin | ↓ Quinidine effect |
| Verapamil | Hypotension |
| RIFAMPIN | |
| Anticoagulants (oral) | ↓ Anticoagulation |
| Barbiturates | ↓ Barbiturate effect |
| β-Adrenergic blockers | ↓ β Blockade |
| Chloramphenicol | ↓ Chloramphenicol effect |
| Contraceptives (oral) | ↓ Contraception |
| Corticosteroids | ↓ Corticosteroid effect |
| Cyclosporine | ↓ Cyclosporine effect |
| Isoniazid | ↑ Hepatotoxicity |
| Ketoconazole | ↓ Effects (both drugs) |
| Phenytoin | ↓ Phenytoin effect |
| Quinidine | ↓ Quinidine effect |
| Theophylline | ↓ Theophylline effect |
| Verapamil | ↓ Verapamil effect |
| THEOPHYLLINE | |
| Barbiturates | ↓ Theophylline effect |
| β-Adrenergic blockers | ↑ Theophylline toxicity |
| Carbamazepine | ↓ Theophylline effect |
| Cimetidine | ↑ Theophylline toxicity |
| Erythromycins | ↑ Theophylline toxicity |
| Fluoroquinolones | ↑ Theophylline toxicity |
| Influenza vaccine (viral) | ↑ Theophylline toxicity |
| Interferon | ↑ Toxicity? |
| Marijuana smoking | ↓ Theophylline effect |
| Phenytoin | ↓ Effect (both drugs) |
| Rifampin | ↓ Theophylline effect |
| Tobacco smoking | ↓ Theophylline effect |
| Troleandomycin | ↑ Theophylline toxicity |
| TRIMETHOPRIM/SULFAMETHOXAZOLE | |
| Anticoagulants (oral) | ↑ Anticoagulation |
| Antidepressants (tricyclic) | Depression |
| Mercaptopurine | ↓ Antileukemia effect |
| Methotrexate | Megaloblastic anemia |
| VALPROATE | |
| Barbiturates | ↑ Phenobarbital toxicity |
| Benzodiazepines | ↑ Diazepam toxicity |
| Carbamazepines | ↓ Valproate effect |
| Cimetidine | ↑ Valproate toxicity? |
| Ethosuximide | ↑ Ethosuximide toxicity? |
| Phenytoin | ↑ Phenytoin toxicity |
Reference:
Nelson Textbook of Pediatrics 18th Edition