Lamotrigine

LAMICTAL is indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older: • partial-onset seizures. • primary generalized tonic-clonic (PGTC) seizures. • generalized seizures of Lennox-Gastaut syndrome. Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood 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 of LAMICTAL in the acute treatment of mood episodes has not been established.

The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state. The relevance of these models to human epilepsy, however, is not known. One proposed mechanism of action of lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels.

• 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. LAMICTAL Starter Kits and LAMICTAL ODT Patient Titration Kits are available for the first 5 weeks of treatment. • Do not restart LAMICTAL 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). Epilepsy: • Adjunctive therapy—See Table 1 for patients older than 12 years and Tables 2 and 3 for patients aged 2 to 12 years. • Conversion to monotherapy—See Table 4. Bipolar disorder: See Tables 5 and 6.

LAMICTAL is contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients. Hypersensitivity to the drug or its ingredients. ( Boxed Warning, 4 )

Boxed warning (serious skin rashes lamictal): can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.3% to 0.8% in pediatric patients (aged 2 to 17 years) and 0.08% to 0.3% in adults receiving LAMICTAL. • Life-threatening serious rash and/or rash-related death: Discontinue at the first sign of rash, unless the rash is clearly not drug related. ( Boxed Warning, 5.1 ) • Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluate patients immediately if they develop signs or symptoms of systemic inflammation. Discontinue LAMICTAL if an alternative etiology is not established.

The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: • Serious Skin Rashes • Hemophagocytic Lymphohistiocytosis • Multiorgan Hypersensitivity Reactions and Organ Failure • Cardiac Rhythm and Conduction Abnormalities • Blood Dyscrasias • Suicidal Behavior and Ideation • Aseptic Meningitis • Withdrawal Seizures • Status Epilepticus Epilepsy: Most common adverse reactions (incidence ≥10%) in adults were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children included vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, and tremor.

Significant drug interactions with LAMICTAL are summarized in this section. Uridine 5´-diphospho-glucuronyl transferases (UGT) have been identified as the enzymes responsible for metabolism of lamotrigine. Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGT, may also enhance the metabolism of lamotrigine. Those drugs that have been demonstrated to have a clinically significant impact on lamotrigine metabolism are outlined in Table 13. Specific dosing guidance for these drugs is provided in the Dosage and Administration section, and, for women taking estrogen‑containing products, including oral contraceptives, in the Warnings and Precautions section.

Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) in a dry place. 100-mg, peach, scored, shield-shaped tablets debossed with “LAMICTAL” and “100”, bottles of 100 (NDC 0173-0642-55). 150-mg, cream, scored, shield-shaped tablets debossed with “LAMICTAL” and “150”, bottles of 60 (NDC 0173-0643-60). 200-mg, blue, scored, shield-shaped tablets debossed with “LAMICTAL” and “200”, bottles of 60 (NDC 0173-0644-60). Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) in a dry place and protect from light. Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) in a dry place.