Lamitrin is an antiepileptic drug (AED) indicated for: Epilepsy- adjunctive therapy in patients aged 2 years and older: Partial-onset seizures Primary generalized tonic-clonic seizures Generalized seizures of Lennox-Gastaut syndrome Epilepsy- monotherapy in patients aged 16 years and older. Bipolar disorder- patients aged 18 years and older.
The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects.
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Table-4: Escalation Regimen for Lamotrigine in Adults with Bipolar Disorder Weeks 1 & 2: In patients not taking Carbamazepine, Phenytoin, Phenobarbital, Primidone or Valproate: 25 mg daily In patients taking Valproate: 25 mg every other day In patients taking Carbamazepine, Phenytoin, Phenobarbital or Primidone and not taking Valproate: 50 mg daily Weeks 3 & 4: In patients not taking Carbamazepine, Phenytoin, Phenobarbital, Primidone or Valproate: 50 mg daily In patients taking Valproate: 25 mg daily In patients taking Carbamazepine, Phenytoin, Phenobarbital or Primidone and not taking Valproate: 100 mg daily (in divided doses) Week 5: In patients not taking Carbamazepine, Phenytoin, Phenobarbital, Primidone or Valproate: 100 mg daily In patients taking Valproate: 50 mg daily In patients taking Carbamazepine, Phenytoin, Phenobarbital or Primidone and not taking Valproate: 200 mg daily (in divided doses) Week 6: In patients not taking Carbamazepine, Phenytoin, Phenobarbital, Primidone or Valproate: 200 mg daily In patients taking Valproate: 100 mg daily In patients taking Carbamazepine, Phenytoin, Phenobarbital or Primidone and not taking Valproate: 300 mg daily (in divided doses) Week 7: In patients not taking Carbamazepine, Phenytoin, Phenobarbital, Primidone or Valproate: 200 mg daily In patients taking Valproate: 100 mg daily In patients taking Carbamazepine, Phenytoin, Phenobarbital or Primidone and not taking Valproate: up to 400 mg daily (in divided doses)
Adult: Dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, pharyngitis, and rash. Children: Vomiting, diarrhea, infection, fever, abdominal pain, and tremor.
Valproate increases Lamitrin concentrations more than 2-fold. Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease Lamitrin concentrations by approximately 40%. Estrogen-containing oral contraceptives decrease Lamitrin concentrations by approximately 50%. Protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir decrease Lamitrin exposure by approximately 50% and 32% respectively.
Discontinue at the first sign of rash. Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): may occur. Monitor for signs of anemia, unexpected infection, or bleeding. Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors. Aseptic meningitis: Monitor for signs of meningitis.