MECHANISM OF ACTION
Valproic acid decreases the clearance of
lamotrigine.(1)
DISCUSSION
In clinical trials, 6 of 584 (1%) of patients who received
lamotrigine with valproate were hospitalized with rash. Only 4 of 2398
patients who received lamotrigine without valproate were hospitalized. In
pediatric patients receiving concurrent valproate, 1.2% experienced a
serious rash compared with 0.6% of those not receiving concurrent therapy.
(1)
CLINICAL EFFECTS
Concurrent therapy results in increased levels of
lamotrigine, requiring dosage adjustments. Valproic acid levels may also
decrease over the first three weeks of therapy. Coadministration of
valproic acid may increase the risk of potentially life-threatening
lamotrigine-induced rashes.(1)
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
The dosage of lamotrigine should be reduced during
concurrent administration of valproic acid. Refer to the current
manufacturer's prescribing information for lamotrigine for dosing guidelines
for patients receiving concurrent lamotrigine and valproic acid therapy.(1)
PREDISPOSING FACTORS
The incidence of lamotrigine-induced rash has been
shown to be higher in pediatric patients. Although yet to proven, exceeding
the recommended dosage for lamotrigine or exceeding the recommended dose
escalation for lamotrigine may also increase the risk for
lamotrigine-induced rash.(1)
REFERENCES