Reduced bioavailability of moisture-exposed carbamazepine resulting in status epilepticus.
A 28-year-old man with seizures well controlled with carbamazepine (CBZ) and valproate (VPA) developed generalized convulsive status epilepticus three days after his CBZ tablets became wet during a rainstorm while he was camping out. He continued the CBZ but avoided ingesting obviously disintegrating tablets. The VPA was not exposed to excessive moisture. Previous random CBZ blood levels had been in the range of 9-13 micrograms/ml; at the time of admission to the emergency room the level had decreased to 3.8 micrograms/ml. The VPA level did not change significantly from baseline. The moisture-exposed CBZ tablets were of expected weight but were swollen and enlarged. Analysis of these tablets by USP paddle method 2 demonstrated a mean dissolution of 16% at 60 min as compared with > 80% for fresh CBZ tablets. After final dissolution of the moisture-exposed CBZ tablets, normal quantities of active drug were noted. We propose that poor dissolution of moisture-exposed CBZ tablets results in reduced bioavailability. We urge caution in the packaging and storage of CBZ to avoid exposure to moisture.
Bell
W L
WL
Department of Neurology, University of Texas Southwestern Medical Center, Dallas.
Crawford
I L
IL
Shiu
G K
GK
D000328:Adult; D001682:Biological Availability; D002220:Carbamazepine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004340:Drug Contamination; D004356:Drug Storage; D004359:Drug Therapy, Combination; D006801:Humans; D006813:Humidity / Q000009:adverse effects*; D008297:Male; D011891:Rain; D013226:Status Epilepticus / Q000139:chemically induced*; D014635:Valproic Acid / Q000627:therapeutic use
D002220:Carbamazepine; D014635:Valproic Acid