Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.

Article Details

Citation

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
DrugEnzymeKindOrganismPharmacological ActionActions
AcetazolamideCytochrome P450 3A4ProteinHumans
Unknown
Inhibitor
Details
DanazolCytochrome P450 3A4ProteinHumans
Unknown
Inhibitor
Details
DextropropoxypheneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
FidaxomicinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
MetronidazoleCytochrome P450 3A4ProteinHumans
Unknown
Inhibitor
Details
PrimidoneCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
RemacemideCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
DrugsInteraction
Aminophylline
Carbamazepine
The serum concentration of Aminophylline can be decreased when it is combined with Carbamazepine.
Bromotheophylline
Carbamazepine
The serum concentration of Bromotheophylline can be decreased when it is combined with Carbamazepine.
Caffeine
Carbamazepine
The serum concentration of Caffeine can be decreased when it is combined with Carbamazepine.
Carbamazepine
Acetazolamide
The serum concentration of Carbamazepine can be increased when it is combined with Acetazolamide.
Dyphylline
Carbamazepine
The serum concentration of Dyphylline can be decreased when it is combined with Carbamazepine.