Carbamazepine-Drug Interactions: Appropriate Management Minimizes Risk

January 1, 2007

Carbamazepine is associatedwith numerousclinically significantdrug interactions.1 Thiswidely used agent ismost commonly prescribed for eitherseizure disorders or adjunctivepain management.

Carbamazepine is associatedwith numerousclinically significantdrug interactions.1 Thiswidely used agent ismost commonly prescribed for eitherseizure disorders or adjunctivepain management.A complete list of carbamazepineinteractions is far beyond thescope of this overview. Our aimhere is to remind you to check forclinically relevant interactions wheneveryou prescribe this drug.A KEY INDUCER OFDRUG METABOLISMCarbamazepine is a classic inducerof drug metabolism.2 Indeed--along with rifampin, barbiturates,and phenytoin--carbamazepine isan important inducer of hepatic andgut wall cytochrome P-450. It is welldocumented that carbamazepine inducesits own metabolism; this autoinduction,which results in increasedclearance, occurs during the firstfew weeks of therapy.3In recent years, P-glycoprotein(P-gp)--a drug efflux transporterfound in the intestinal lumen, theliver, the kidneys, and the bloodbrainbarrier--has also been recognizedas a major site for significantdrug interactions. It has been speculatedthat modifiers of the cytochromeP-450 3A4 isoenzyme alsoalter P-gp expression; however, thedata on carbamazepine's activity onP-gp are conflicting and furtherstudy is needed. Table 1 providessome important examples of the effect of carbamazepine on otherdrugs used concomitantly.EFFECTS OF OTHER AGENTSON CARBAMAZEPINESeveral therapeutic agents arewell documented to affect the serumconcentrations of carbamazepine.Concurrent use of other medicationto treat seizures, such asphenytoin or phenobarbital, can reduceserum levels of carbamazepine.1 Monitor serum carbamazepinelevels in this setting.Drugs that inhibit the metabolismof carbamazepine may causetoxicity. Table 2 lists several drugsthat may increase serum carbamazepineconcentrations. Monitorcarbamazepine levels when theseagents are added or discontinued. Inaddition, bear in mind that grapefruitjuice has been documented toincrease carbamazepine levels.4

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