Partial Listing of Drug Interactions of Potential Importance in Pediatric Practice






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
 

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