Reduced Bioavailability of Moisture‐Exposed Carbamazepine Resulting in Status Epilepticus

Abstract

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.

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

“…In the case of carbamazepine products this rate of absorption may be especially important. Carbamazepine is very sensitive to moisture and the grade of hydration influences the dissolution in vitro as well as in vivo [16][17][18][19]. This altered rate of dissolution may cause serious side effects (e.g.…”

“…Blood samples were taken in heparin test-tubes just before dosing and 0.5, 1, 1.5, 2, 3, 4,6,8,10,12,14,16,20,24,28 and 32 h postdose through an intravenous cannula. After 32 h the cannula was removed and at time points 48, 56, 72, 80 and 96 h postdose samples were taken by vena punction.…”

Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy

“…However, a decreased bioavailability and other property changes such as hardening and disintegration of CBZ tablets after storage have been reported. These changes have been attributed to the formation of the DH [10][11][12][13][14]. Therefore, characterizing the conversion kinetics of CBZ form III to the DH is of great importance.…”

An unusual case of Lafora body disease

“…Both the withdrawal of sodium valproate, which is known to control absence seizures (Berkovic et al, 1989), and the introduction of carbamazepine, which has been implicated in precipitating both convulsive (Sharma et al, 1992;Bell et al, 1993) and NCSE (Callahan and Noetzel, 1992;So et al, 1994), might have been responsible. The underlying degenerative hsorder may itself predispose to NCSE, either generally or related to carbamazepine, which should therefore be used cautiously in this condition.…”