Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.
Article Details
- CitationCopy to clipboard
Spina E, Pisani F, Perucca E
Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.
Clin Pharmacokinet. 1996 Sep;31(3):198-214. doi: 10.2165/00003088-199631030-00004.
- PubMed ID
- 8877250 [ View in PubMed]
- 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, leading 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-10,11-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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Acetazolamide Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Danazol Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Dextropropoxyphene Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails Fidaxomicin Cytochrome P450 3A4 Protein Humans NoInhibitorDetails Metronidazole Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Primidone Cytochrome P450 3A4 Protein Humans UnknownInducerDetails Remacemide Cytochrome P450 3A4 Protein Humans NoInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAminophyllineCarbamazepine The serum concentration of Aminophylline can be decreased when it is combined with Carbamazepine. BromotheophyllineCarbamazepine The serum concentration of Bromotheophylline can be decreased when it is combined with Carbamazepine. CaffeineCarbamazepine The serum concentration of Caffeine can be decreased when it is combined with Carbamazepine. CarbamazepineAcetazolamide The serum concentration of Carbamazepine can be increased when it is combined with Acetazolamide. DyphyllineCarbamazepine The serum concentration of Dyphylline can be decreased when it is combined with Carbamazepine.