Lamotrigine

Brand Names: Lamotrigine

Drug Class: Anti-epileptic Agent

Overview

11 DESCRIPTION Lamotrigine, USP an AED of the phenyltriazine class, is chemically unrelated to existing AEDs. Lamotrigine’s chemical name is 3,5-diamino-6-(2,3-dichlorophenyl)- as -triazine, its molecular formula is C 9 H 7 N 5 Cl 2 , and its molecular weight is 256.09. Lamotrigine, USP is a white to pale cream-colored powder and has a pK a of 5.7. Lamotrigine, USP is slightly soluble in 0.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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.

Indications

  • 1 INDICATIONS AND USAGE Lamotrigine orally disintegrating tablets are 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. ( 1.1 ) 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. ( 1.

Common Doses

  • 100 mg
  • 25 mg
  • 50 mg
  • 200 mg

Dosage

2 DOSAGE AND ADMINISTRATION Dosing is based on concomitant medications, indication, and patient age. ( 2.1 , 2.2 , 2.3 , 2.4 ) To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. Lamotrigine Orally Disintegrating Tablets Patient Titration Kits are available for the first 5 weeks of treatment. ( 2.1 , 16 ) Do not restart lamotrigine orally disintegrating tablets in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. ( 2.1 , 5.

Black Box Warning

WARNING: SERIOUS SKIN RASHES Lamotrigine 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 lamotrigine. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking lamotrigine as adjunctive therapy.

Contraindications

  • 4 CONTRAINDICATIONS Lamotrigine is contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see Boxed Warning , Warnings and Precautions ( 5.1 , 5.3 )]. Hypersensitivity to the drug or its ingredients. ( Boxed Warning , 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: Serious Skin Rashes [see Warnings and Precautions (5.1) ] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5.2) ] Multiorgan Hypersensitivity Reactions and Organ Failure [see Warnings and Precautions (5.3) ] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions (5.4) ] Blood Dyscrasias [see Warnings and Precautions (5.5) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.

Interactions

  • 7 DRUG INTERACTIONS Significant drug interactions with lamotrigine 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.