MECHANISM OF ACTION
Some anticonvulsants may induce the metabolism of
posaconazole by CYP P-450-3A4.(1,2)
DISCUSSION
Concurrent phenytoin (200 mg daily) decreased posaconazole
area-under-curve (AUC) and maximum concentration (Cmax) by 50% and 41%,
respectively.(1,2) Both phenytoin AUC and Cmax increased by 16%.(2)
CLINICAL EFFECTS
Concurrent use of some anticonvulsants such as
carbamazepine, phenobarbital, primidone,(1) and phenytoin(1,2) may result in
decreased levels and clinical effectiveness of posaconazole.
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
The UK manufacturer of posaconazole states that
concurrent use of carbamazepine, phenobarbital, primidone, and phenytoin
should be avoided unless the benefit to the patient outweighs the risk of
concurrent therapy.(1)
PREDISPOSING FACTORS
None determined.
REFERENCES