MECHANISM OF ACTION
Carbamazepine, phenobarbital, and phenytoin may induce
the metabolism of erlotinib by CYP P-450-3A4.(1)
DISCUSSION
Pretreatment and concurrent therapy with rifampin, another CYP
P-450-3A4 inducer, increased erlotinib clearance by 3-fold and decreased the
erlotinib area-under-curve (AUC) by 66% to 80%. This is equivalent to a
dose of about 30 mg to 50 mg in NSCLC.(1)
CLINICAL EFFECTS
Concurrent use of carbamazepine, phenobarbital, and/or
phenytoin may result in decreased levels and effectiveness of erlotinib.(1)
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
Consider alternatives to carbamazepine, phenobarbital,
and phenytoin in patients receiving erlotinib. If concurrent therapy cannot
be avoided, consider increasing the dosage of erlotinib as tolerated at two
week intervals while closely monitoring the patient. The highest dosage
studied with a concurrent CYP P-450-3A4 inducer (rifampin) is 450 mg.(1)
PREDISPOSING FACTORS
None determined.
REFERENCE