FDA Approves Lamotrigine for Adjunctive Therapy in Epilepsy and Maintenance in Bipolar I Disorder

Not reported in label.

Lamotrigine is indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older for partial-onset seizures, primary generalized tonic-clonic (PGTC) seizures, and generalized seizures of Lennox-Gastaut syndrome. Epilepsy—monotherapy for conversion to monotherapy in patients aged 16 years and older with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. Safety and effectiveness have not been established as initial monotherapy, for conversion from other AEDs, or for simultaneous conversion from 2 or more concomitant AEDs. Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness in the acute treatment of mood episodes has not been established.

Dosing is based on concomitant medications, indication, and patient age. To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. Do not restart lamotrigine in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing products, including oral contraceptives. Discontinuation: Taper over a period of at least 2 weeks (approximately 50% dose reduction per week). Specific dosing tables are referenced for adjunctive therapy in patients older than 12 years and aged 2 to 12 years, for conversion to monotherapy, and for bipolar disorder. A therapeutic plasma concentration range has not been established; dosing should be based on therapeutic response.

Trial data not available in label.

There is a risk of severe, potentially life-threatening rash. The risk may be increased by coadministration with valproate, exceeding the recommended initial dose, or exceeding the recommended dose escalation, but cases have occurred in the absence of these factors. The risk of nonserious rash may be increased when the recommended initial dose and/or rate of dose escalation is exceeded and in patients with a history of allergy or rash to other AEDs. It is recommended that lamotrigine not be restarted in patients who discontinued due to rash unless potential benefits clearly outweigh risks.

For epilepsy, lamotrigine serves as an adjunctive therapy for specific seizure types in patients aged 2 and older and as a conversion to monotherapy agent for adults with partial-onset seizures on specific single-AED regimens. For bipolar I disorder, it is a maintenance treatment to delay mood episodes following acute treatment, but it is not for acute manic/mixed episode treatment. Its use requires careful dose titration and monitoring due to the risk of rash and significant drug interactions, particularly with medications affecting glucuronidation.