Clinically significant pharmacokinetic drug interactions with carbamazepine

Edoardo Spina, Franco Pisani, Emilio Perucca

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, lending to the possibility of drug interactions. The most important interactions affecting carbamazepine pharmacokinetics are those resulting in induction or inhibition of its metabolism. Phenytoin, phenobarbital (phenobarbitone) and primidone accelerate the elimination of carbamazepine, probably by stimulating cytochrome P450 (CYP) 3A4, and reduce plasma carbamazepine concentrations to a clinically important extent. Inhibition of carbamazepine metabolism and elevation of plasma carbamazepine to potentially toxic concentrations can be caused by stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid, metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol and (dextropropoxyphene) propoxyphene. In other cases, toxic symptoms may result from elevated plasma concentrations of the active metabolite carbamazepine-l0, 11-epoxide, due to the inhibition of epoxide hydrolase by valproic acid (sodium valproate), valpromide, valnoctamide and progabide. Carbamazepine is a potent inducer of CYP3A4 and other oxidative enzyme system in the liver, and it may also increase glucuronyltransferase activity. This results in the acceleration of the metabolism of concurrently prescribed anticonvulsants, particularly valproic acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine and remacemide. The metabolism of many other drugs such as tricyclic antidepressants, antipsychotics, steroid oral contraceptives, glucocorticoids, oral anticoagulants, cyclosporin, theophylline, chemotherapeutic agents and cardiovascular drugs can also be induced, leading to a number of clinically relevant drug interactions. Interactions with carbamazepine can usually be predicted on the basis of the pharmacological properties of the combined drug, particularly with respect to its therapeutic index, site of metabolism and ability to affect specific drug metabolising isoenzymes. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential, and careful dosage adjustments based on serum drug concentration monitoring and clinical observation represent the mainstays for the minimisation of risks associated with these interactions.

Original languageEnglish
Pages (from-to)198-214
Number of pages17
JournalClinical Pharmacokinetics
Volume31
Issue number3
Publication statusPublished - 1996

Fingerprint

Carbamazepine
Drug Interactions
Pharmacokinetics
Valproic Acid
Dextropropoxyphene
Poisons
Phenobarbital
Pharmaceutical Preparations
Anticonvulsants
Ethosuximide
Primidone
Danazol
Epoxide Hydrolases
Social Adjustment
Clonazepam
Cardiovascular Agents
Cytochrome P-450 CYP3A
Polypharmacy
Glucuronosyltransferase
Trigeminal Neuralgia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Clinically significant pharmacokinetic drug interactions with carbamazepine. / Spina, Edoardo; Pisani, Franco; Perucca, Emilio.

In: Clinical Pharmacokinetics, Vol. 31, No. 3, 1996, p. 198-214.

Research output: Contribution to journalArticle

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