Lamotrigine

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[edit] BRAND NAMES

[edit] STRUCTURE

Lamotrigine.jpg

[edit] MECHANISM OF ACTION

Lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).

[edit] INDICATIONS

Epilepsy
Lamotrigine is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome:

  • Adjunctive therapy in patients ≥2 years of age (USA and Europe):
    • partial seizures
    • primary generalized tonic-clonic seizures
    • generalized seizures of Lennox-Gastaut syndrome
  • monotherapy in patients ≥16 years of age in USA and ≥12 years of age in Europe: conversion to monotherapy in patients with partial seizures who are receiving treatment with carbamazepine, phenobarbital, phenytoin, primidone, or valproate as the single antiepileptic drug.


Bipolar Disorder
Lamotrigine is also a mood stabilizer and has been proven to be effective in preventing depression in patients with bipolar disorder type I. A recent study suggests that olanzapine, an atypical antipsychotic, is more effective than lamotrigine in the prevention of depressive episodes in patients with bipolar disorder.[1]

  • Bipolar Disorder in patients ≥18 years of age: 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 (USA and Europe).


  • Major depression (Off label): Lamotrigine is also used off-label as an adjunct in treating major depression

[edit] DOSAGE

Lamotrigine can be taken once or twice a day. A slow introduction of the drug is of benefit to lessen the risk of allergic skin rash, including Stevens–Johnson syndrome, DRESS syndrome and toxic epidermal necrolysis.


Medscape link for Lamotrigine dosage

[edit] CONTRAINDICATIONS

Patients who have demonstrated hypersensitivity to the drug

[edit] WARNINGS AND PRECAUTIONS

Cases of life-threatening serious rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and/or rash-related death, have been caused by Lamotrigine. The rate of serious rash is greater in pediatric patients (8 per 1,000) than in adults (3 per 1,000). Additional factors that may increase the risk of rash include:

  • Coadministration with Valproic acid
  • Exceeding recommended initial dose of Lamotrigine
  • Exceeding recommended dose escalation of Lamotrigine

Nearly all cases of life-threatening rashes caused by Lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months).

Benign rashes are also caused by Lamotrigine; however, it is not possible to predict which rashes will prove to be serious or life threatening. Lamotrigine should be discontinued at the first sign of rash, unless the rash is clearly not drug relatedDiscontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring.

  • Lamotrigine increases the risk of developing aseptic meningitis

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US) Lamotrigine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

[edit] SIDE EFFECTS

  • Most common adverse reactions (incidence ≥10%) in adult epilepsy clinical studies were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children in epilepsy clinical studies included vomiting, infection, fever, accidental injury, pharyngitis, abdominal pain, and tremor.
  • Most common adverse reactions (incidence >5%) in adult bipolar clinical studies were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia
  • Serious: Stevens-Johnson rash (See WARNINGS AND PRECAUTIONS)

[edit] RELATED LINKS

Pharmacology of Antiepileptic Drugs

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/24885966