MECHANISM OF ACTION
Carbamazepine, phenobarbital, and phenytoin may induce
the metabolism of everolimus by CYP P-450-3A4.(1)
DISCUSSION
In healthy subjects, concurrent use of rifampin, another strong
inhibitor of CYP P-450-3A4, decreased everolimus area-under-curve (AUC) and
maximum concentration (Cmax) by 64% and 58%, respectively.(1)
CLINICAL EFFECTS
Concurrent use of carbamazepine, phenobarbital, or
phenytoin may result in decreased levels and effectiveness of everolimus.(1)
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
The US manufacturer of everolimus states that
concurrent use with strong CYP P-450-3A4 inducers such as carbamazepine,
phenobarbital, or phenytoin should be avoided. If concurrent use is
warranted, consider increasing the dose of everolimus from 10 mg daily to 20
mg daily in 5 mg increments.(1)
PREDISPOSING FACTORS
None determined.
REFERENCE