MECHANISM OF ACTION
Carbamazepine, phenytoin, phenobarbital and primidone
may induce the metabolism of lamotrigine by the CYP P-450 enzyme system.(1)
DISCUSSION
In 24 epileptic adults taking carbamazepine, phenytoin,
phenobarbital, or primidone, the time to maximum concentration (Tmax),
half-life, and apparent plasma clearance for a single dose of lamotrigine
were 2.3 hours, 14.4 hours, and 1.10 ml/min/kg, respectively. In 179
healthy adults taking no other medications, these values were 2.2 hours,
32.8 hours, and 0.44 ml/min/kg, respectively.(1)
CLINICAL EFFECTS
The concurrent use of carbamazepine, phenytoin,
phenobarbital, or primidone with lamotrigine without valproate and without
dosage adjustments may result in decreased levels and clinical effectiveness
of lamotrigine.(1) Coadministration of lamotrigine and valproic acid with
either carbamazepine, phenytoin, or phenobarbital may result in elevated
lamotrigine concentrations.(2)
SEVERITY LEVEL
3-Moderate Interaction: Assess the risk to the patient and
take action as needed.
PATIENT MANAGEMENT
Patients receiving concurrent therapy with lamotrigine
and carbamazepine, phenytoin, phenobarbital, or primidone without valproate
should be observed for decreased lamotrigine levels and clinical
effectiveness. The dose of lamotrigine may need to be adjusted if these
agents are added to or removed from lamotrigine therapy. Refer to the
current lamotrigine prescribing information for information on dosage
adjustments.
PREDISPOSING FACTORS
None determined.
REFERENCES