MECHANISM OF ACTION
Carbamazepine, phenobarbital, and phenytoin may induce
the metabolism of maraviroc by CYP P-450-3A4.(1)
DISCUSSION
In a study in 12 subjects, concurrent rifampin (600 mg daily,
another inducer of CYP P-450-3A4) decreased the minimum concentration
(Cmin), area-under-curve (AUC), and maximum concentration (Cmax) of
maraviroc (100 mg twice daily) by 78%, 63.2%, and 66.3%, respectively.(1)
CLINICAL EFFECTS
Concurrent use of carbamazepine, phenobarbital, or
phenytoin in the absence of an inhibitor of CYP P-450-3A4 and without a
dosage adjustment of maraviroc may result in decreased levels and
effectiveness of maraviroc.(1)
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
The US manufacturer of maraviroc states that patients
receiving therapy with inducers of CYP P-450-3A4, such as carbamazepine,
phenobarbital, or phenytoin who are not also receiving an inhibitor of CYP
P-450-3A4 should receive a dose of 600 mg maraviroc twice daily.(1)
PREDISPOSING FACTORS
This interaction may be more severe in patients with
renal impairment.(1)
REFERENCE