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1 Clinical Pharmacist, Internal Medicine, Department of Pharmacy, Foothills
Medical Centre, Calgary, Alberta, Canada
2 Professor, Faculty of Medicine, University of Calgary; Chief, Division of
General Internal Medicine, Calgary Health Region; Head, Division of General
Internal Medicine, University of Calgary, Calgary
Reprints: Mr. Bates, Foothills Medical Centre, 1403 29th St. NW, Calgary, AB, Canada T2N 2T9, fax 403/944-4893, duane.bates{at}calgaryhealthregion.ca
OBJECTIVE: To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
CASE SUMMARY: 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.
DISCUSSION: 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.
Key Words: carbamazepine, lopinavir, nelfinavir, ritonavir
Published Online, May 23, 2006. www.theannals.com, DOI 10.1345/aph.1G630
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