Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
OBJECTIVE
To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.


METHODS
A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.


CONCLUSIONS
Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966-May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.


CONCLUSIONS
An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine-protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25-50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3-5 days after the protease inhibitors are started.
Bates
Duane E
DE
Internal Medicine, Department of Pharmacy, Foothills Medical Centre, Calgary, Alberta, Canada. duane.bates@calgaryhealthregion.ca
Herman
Robert J
RJ
D000927:Anticonvulsants / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001772:Blood Cell Count; D002220:Carbamazepine / Q000009:adverse effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008111:Liver Function Tests; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects* / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use; D012894:Sleep Stages / Q000187:drug effects; D019562:Viral Load
D000927:Anticonvulsants; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D002220:Carbamazepine; D019888:Nelfinavir; D019438:Ritonavir