Carbamazepine: Watch for Many Potential Drug …

1 DrugINTERACTIONS: insights and observations carbamazepine : Watch for Many Potential Drug Interactions John R. Horn, PharmD, FCCP, and Phillip Hansten, PharmD. concentration of susceptible object bamazepine. Discontinuation of an Drs. Horn and Hansten are both pro- drugs by 50%. For many drugs, this de- inducer may result in increased carba- fessors of pharmacy at the University gree of reduction in plasma concentra- mazepine concentrations and Potential of Washington School of Pharmacy. tion will lead to a reduction in efficacy. toxicity. For an electronic version of this arti- carbamazepine is primarily metabo- Oxcarbazepine (Trileptal) is a related cle, including references if any, visit lized by CYP3A4 to an active metabo- antiepileptic drug.

2 It too is metabolized lite that has about the same efficacy as by CYP3A4 and is an enzyme inducer;. the parent compound. Drugs that in- however, fewer data are available hibit the metabolism of carbamazepine regarding its effects on other drugs. he January 2008 edition of this frequently lead to accumula- Pending further studies, it T column, entitled Stopping Medi- cations Can Cause Adverse Ef- fects (please visit Times. tion and signs of toxicity. Since carbamazepine has a fairly narrow therapeutic Careful monitoring assume would be prudent to that bazepine has a similar oxcar- com/StopMedications), discussed the range, one should be alert for is very interaction profile as car- risk associated with withdrawing an evidence of elevated plasma important bamazepine.

3 One compar- enzyme inducer, carbamazepine , when concentrations, such as dizzi- coadministered with an object drug ness, drowsiness, nausea, if an induc- ative study on the induc- tion effects of the 2 drugs whose elimination is susceptible to vomiting, confusion, and er is coad- found that carbamazepine induction. During concurrent adminis- vision or gait disturbances ministered was a more potent inducer tration of an inducer, the object drug when a drug that inhibits dose may be titrated upward to main- CYP3A4 is coadministered. with carba- of CYP3A4 than oxcar- tain therapeutic effect.

4 If the inducer is Coadministration of inhibitors mazepine. carbamazepine repre- discontinued, the induction will slowly should be accompanied by sents a drug with very dissipate, and the metabolism of the careful monitoring of carbamazepine complex drug interaction Potential . Its object drug will return to normal. If the plasma concentrations and patient narrow therapeutic range and potency dose of the object drug is not reduced, response. carbamazepine side effects as an inducer make it imperative to toxicity may occur. may be apparent within 2 to 3 days of carefully monitor patients receiving carbamazepine is an inducer of sev- initiating a drug that inhibits carba- carbamazepine with other drugs.

5 It is eral Potential pathways of drug elimi- mazepine metabolism. likely to affect the elimination of a wide nation, including CYPs 1A2, 2C9, and Because carbamazepine is an induc- range of drugs and to be affected by 3A4, as well as the active transporter er of CYP3A4 and a substrate for the many common therapeutic agents. P-glycoprotein. Any drug that under- enzyme, carbamazepine induces its Carefully review the drug profile of any goes metabolism via CYP1A2, CYP2C9, own metabolism. Other inducers of patient receiving carbamazepine for or CYP3A4 or is a substrate for the P- CYP3A4 can affect carbamazepine , Potential drug interactions.

6 PT. glycoprotein transporter, is likely to be however, reducing its plasma concen- affected by carbamazepine administra- trations. tion, however. The list of drugs that The result of an inducer on carba- may potentially interact with carba- mazepine would be to reduce its plas- mazepine is very ma concentrations and efficacy. While o n l i n e The recognition of interactions re- more of the active metabolite of carba- For lists of selected drugs that sulting from the induction of elimina- mazepine is likely to be formed, the interact with carbamazepine , please tion is usually rather poor.

7 This is due to metabolism of this metabolite also visit the slow onset of the interaction (1 to appears to be inducible. This complex carbamazepine . 2 weeks) and its presentation as a effect makes it very difficult to predict gradual reduction in the therapeutic what net effect will be seen in a patient. 8. efficacy of the object drug. It is typical Careful monitoring is very important if For a list of references, go to: for carbamazepine to reduce the plasma an inducer is coadministered with car- Pharmacy Times | February 2008 n 37. FOR WEB ONLY.

8 Table 1 Table 3. Selected Drugs Whose Selected Drugs That May Elimination May Be Decrease carbamazepine Increased by carbamazepine Concentrations Amitriptyline Efavirenz (Sustiva). Aripiprazole (Abilify) Nevirapine (Viramune). Atorvastatin (Lipitor) Phenytoin (Dilantin). Citalopram (Celexa) Phenobarbital Clozapine (Clozaril) Rifampin (Rifadin). Contraceptives, Oral Rifapentine (Priftin). Cyclosporine (Neoral) St. John's wort Felbamate (Felbatol). Felodipine (Plendil). Lamotrigine (Lamictal). Lovastatin (Mevacor). Methadone Midazolam (Versed).

9 Nefazodone Nifedipine (Procardia). Prednisolone Quetiapine (Seroquel). Risperidone (Risperdal). Simvastatin (Zocor). Sirolimus (Rapamune). Tacrolimus (Prograf). Theophylline Thyroid Hormone Warfarin (Coumadin). Ziprasidone (Geodon). Table 2. Selected Drugs That May Increase carbamazepine Concentrations Amprenavir (Agenerase). Cimetidine (Tagamet). Clarithromycin (Biaxin). Danazol (Danocrine). Diltiazem (Cardizem). Erythromycin (E-Mycin). Fluconazole (Diflucan). Fluoxetine (Prozac). Fluvoxamine (Luvox). Grapefruit Juice Ketoconazole (Nizoral).

10 Itraconazole (Sporanox). Posaconazole (Noxafil). Propoxyphene (Darvon). Ritonavir (Norvir). Verapamil (Calan). Voriconazole (Vfend).