Lamotrigine

Actions

• Blocks voltage-dependent Na+ channels at high firing frequencies.
• Enhances H current.
• Modulates kainate receptors.

Metabolism

Hepatic

Enzymes involved

• UGT

Elimination

Renal 65%

Therapeutic serum concentration range

2-20 μg/ml

Half-life

18-30 hours

Plasma protein binding

55%

Important side-effects

Serious dermatologic reactions including Stevens-Johnson syndrome and TEN and angioedema. Inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in adults.

Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms (DRESS).

Suicidal behavior and ideation.

Blood dyscrasias.

Aseptic meningitis.

Indications

Focal seizures with or without generalization.

Primarily generalized tonic-clonic seizures.

Absence seizures.

May aggravate myoclonic seizures.

Dosing recommendation

As monotherapy

Start with 25 mg/day for 2 weeks.

Increase to 50 mg/day for 2 weeks and further increases by 50 mg/day every 1–2 weeks.

Target dose: 100–300 mg/day divided in 1-2 doses.

Combination with valproate

Start with 25 mg every other day for 2 weeks.

Increase to 25 mg/day for 2 weeks and further increase by 25-50 mg/day every 1-2 weeks.

Target dose: 100-200 mg/day divided in 1-2 doses.

Combination with inducer of UGT enzyme, without valproate

Start with 50 mg/day in a single dose for 2 weeks.

Increase to 100 mg/day divided in 2 doses for 2 weeks and further increase by 50-100 mg/day every 1-2 weeks.

Target dose: 300-500 mg/day divided in 2 doses.

Some estrogen-containing oral contraceptives have been shown to decrease serum concentrations of lamotrigine. Dose adjustments will be necessary in most patients who start or stop estrogen-containing oral contraceptives while taking lamotrigine.

Renal impairment

Reduction of the initial dose, increments and target dose is advised in patients with severely impaired renal function.

Hepatic impairment

Reduction by 50% of the initial dose, increments and target dose is advised in patients with moderately impaired hepatic function (Child-Pugh class B) and by 75% in patients with severely impaired hepatic function (Child-Pugh class C).

Serum concentration changes during pregnancy

Total level decreases by 30-75%. Free fraction level decreases by 30-75%.