Carbamazepine toxicity resulting from generic substitution

Abstract

Generic substitution is practiced widely in both hospital and community settings. There have been several reports of reduced serum concentrations and seizure exacerbation following generic substitution of Tegretol. We describe the first 2 cases of carbamazepine toxicity resulting from the substitution of Tegretol with Epitol. Two 6-year-old children experienced increases in the maximum serum carbamazepine concentration, one of 22% and one of 41%. Both became asymptomatic when their serum concentrations were lowered and had no residual effects.

Recommendations of the Italian League Against Epilepsy Working Group on Generic Products of Antiepileptic Drugs

“…In contrast to the lack of controlled studies, there are several published reports of loss or worsening of seizure control (Koch and Allen, 1978;Pedersen and Dam, 1985;McDonald, 1987;Wyllie et al, 1987;Sachdeo and Belendiuk, 1987;Hartley et al, 1990;Welty et al, 1992;Jain, 1993;Meyer and Straughn, 1993;Guberman and Corman, 2000;Burkhardt et al, 2004;Wilner, 2004;Haskins et al, 2005) or appearance of adverse events (Finestone and Williams, 1985;Gilman et al, 1993;Brown et al, 1998;Guberman and Corman, 2000;Wilner, 2004;Haskins et al, 2005) following substitution of a brand AED with a generic. Many of these reports date back several years, when regulatory requirements for the approval of generics were not as stringent as those currently in force in major industrialized countries (Richens, 1997;American Medical Association, 2006) and therefore some products of inadequate quality found their way into the market (Bochner et al, 1972;Sansom et al, 1975;Manson et al, 1975;Stewart et al, 1975;Tammisto et al, 1976;Hodges et al,1986;Mikati et al, 1992;Soryal and Richens, 1992;Meyer et al, 1992;Rosenbaum et al, 1994).…”

Bioavailability of carbamazepine from four different products and the occurrence of side effects

“…In the last few years several publications [1][2][3][4][5] were written in which the occurrence of side effects after changing from one carbamazepine product to another are described. In different countries experiments were started to find some explanations for this phenomenon [6 -8].…”

Neue Bioäquivalenzkriterien der Europäischen Arzneimittelagentur

“…Generation bekannte Problem der Sicherstellung einer therapeutischen Äquivalenz [10,12,17] aktualisiert. Eine Vielzahl von Publikationen weist darauf hin, dass es im Rahmen von Umstellungen unter verschiedenen Prä-paraten mit gleichem Wirkstoff zu Problemen der Verträglichkeit und/oder der Wirksamkeit kommen kann (z.…”