MECHANISM OF ACTION
Carbamazepine, phenobarbital, and phenytoin may induce
the metabolism of exemestane by CYP P-450-3A4.(1)
DISCUSSION
In a study in 10 healthy postmenopausal subjects, pretreatment
with rifampin (600 mg daily for 14 days), another inducer of CYP P-450-3A4,
decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a
single dose of exemestane (25 mg) by 54% and 41%, respectively.(1)
CLINICAL EFFECTS
Concurrent use of carbamazepine, phenobarbital, or
phenytoin may result in decreased levels and effectiveness of exemestane.(1)
SEVERITY LEVEL
3-Moderate Interaction: Assess the risk to the patient and
take action as needed.
PATIENT MANAGEMENT
The US manufacturer of exemestane recommends that
patients receiving concurrent therapy with a potent CYP P-450-3A4 inducer
such as carbamazepine, phenobarbital, or phenytoin receive 50 mg of
exemestane daily after a meal.(1) The dosage of exemestane may need to be
adjusted if carbamazepine, phenobarbital, or phenytoin is discontinued.
PREDISPOSING FACTORS
None determined.
REFERENCE