Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction.
Verapamil (120 mg three times a day) was given as adjunctive therapy to six patients with refractory partial epilepsy who were receiving carbamazepine (CBZ). Within a few days symptoms of CBZ neurotoxicity developed in all six patients. There was a mean rise of 46% in total and 33% in free plasma CBZ concentrations in five of these patients (p less than 0.01), and a simultaneous fall of 36% in the ratio of the principal metabolite, CBZ-10,11-epoxide, to CBZ (p less than 0.001). Two patients with mild symptoms were rechallenged with a lower verapamil dosage (120 mg twice a day) and showed similar rises in CBZ concentration and recurrent neurotoxic symptoms. Verapamil increased the area under the CBZ concentration/time curve during a dose interval by 42% in another patient. Withdrawal of verapamil was associated with a decline in circulating CBZ concentration from 12 mg/l to 7 mg/l and seizure breakthrough in a further patient who was receiving both drugs long term. These results suggest that verapamil inhibits the metabolism of CBZ to an extent likely to have important clinical repercussions.
Macphee
G J
GJ
McInnes
G T
GT
Thompson
G G
GG
Brodie
M J
MJ
D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D002986:Clinical Trials as Topic; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D012640:Seizures / Q000188:drug therapy; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects*
D002220:Carbamazepine; D014700:Verapamil