Two 6-year-old children with carbamazepine (CBZ) toxicity, reported from the University of Miami School of Medicine, were found to have 22% and 41% increases in serum CBZ levels after substitution of Tegretol with the generic brand, Epitol, because of insurance company policies. Adverse effects included lethargy, ataxia, slurred speech, and nystagmus. When dosage was adjusted, symptoms of toxicity resolved. [1]
COMMENT. Generic substitution of Tegretol has previously been associated with lowered serum levels of CBZ and seizure exacerbation. Reduced bioavailability is also reported with moisture-exposed CBZ, resulting in status epilepticus [2]. Gilman et al have documented 2 cases of increased bioavailability with Epitol substitution, one of 4 generic carbamazepine products available in the US. In 1988, 70 million CBZ tablets were recalled because of bioinequivalence and clinical seizure exacerbation [3]. Factors other than generic substitution may account for significant variations in CBZ concentrations, including interlot variability, exposure of drug to excessive heat or moisture, food and drug interactions, sample timing, and patient compliance.