Lamotrigine

BRAND NAMES:
LAMICTAL: LAMICTAL comes in several dose forms, including tablets, chewable dispersible pills, extended-release tablets, and oral disintegrating tablets. It works by reducing aberrant and excessive nerve cell activity in the brain, which helps to avoid seizures or fits.
MECHANISM OF ACTION :
The mechanism of action for lamotrigine is not fully understood. It is a triazine, and studies have demonstrated that lamotrigine preferentially binds to and blocks voltage-gated sodium channels, stabilizing presynaptic neuronal membranes while reducing glutamate and aspartate release. Researchers have found no evidence that lamotrigine has a substantial influence on other neurotransmitters such as serotonin, norepinephrine, or dopamine. There is a suggestion that lamotrigine interacts with voltage-activated calcium-gated channels, contributing to its wide activity. In vitro investigations have also indicated that lamotrigine inhibits dihydrofolate reductase, raising concerns about its teratogenicity. Lamotrigine exhibits first-order kinetics and has a half-life of 29 hours. 
PHARMACOKINETICS :
Absorption: Lamotrigine is quickly and completely absorbed following oral administration, with minimal first-pass metabolism (absolute bioavailability of 98%). The bioavailability is unaffected by eating. Peak plasma concentrations range from 1.4 to 4.8 hours after medication delivery. Regarding rate and amount of absorption, lamotrigine chewable/dispersible tablets performed similarly to compressed tablets when dispersed in water, chewed and swallowed, or taken whole. Lamotrigine orally disintegrating pills, whether disintegrated in the mouth or ingested whole with water, had the same rate and amount of absorption as compressed tablets when swallowed with water.
Distribution: The average estimated volume of distribution of lamotrigine following oral administration ranged between 0.9 and 1.3 L/kg.
Metabolism: Lamotrigine is metabolized mostly through the glucuronic acid conjugation process with the main metabolite being an inert 2-N-glucuronide conjugate. After administering 240 mg of C-lamotrigine to 6 healthy volunteers, 94% was recovered in urine and 2% in feces. Urine radioactivity included unaltered lamotrigine (10%), 2-Nglucuronide (76%), 5-N-glucuronide (10%), 2-N-methyl metabolite (0.14%), and unexplained minor metabolites (4%). 
Elimination: The typical elimination half-life of lamotrigine ranges between 14 and 59 hours. The value is determined by the dose administered, concurrent medication therapy, and disease status. In one pharmacokinetic investigation, healthy participants had a half-life ranging from 22.8 to 37.4 hours. It was found that enzyme-inducing antiepileptic medicines, including phenobarbital, phenytoin, and carbamazepine, shorten the half-life of lamotrigine. On the other hand, valproic acid increases the half-life of lamotrigine.
PHARMACODYNAMICS:
Folate metabolism: In vitro, lamotrigine inhibited dihydrofolate reductase, an enzyme that converts dihydrofolate to tetrahydrofolate. Inhibition of this enzyme may disrupt the production of nucleic acids and proteins. During organogenesis, pregnant rats received oral daily dosages of lamotrigine, which lowered fetal, placental, and maternal folate concentrations. Teratogenesis has been related to significantly lower folate levels. Folate concentrations were likewise lowered in male rats given repeated oral lamotrigine dosages. Folic acid supplementation largely restored reduced amounts to normal.
Cardiovascular effects: In vitro investigations indicate that lamotrigine has class IB antiarrhythmic action at clinically relevant doses. It blocks human cardiac sodium channels with rapid onset and offset kinetics and considerable voltage dependency, similar to other Class IB antiarrhythmic drugs. In a comprehensive QT investigation, lamotrigine did not impede ventricular conduction (widen QRS) in healthy individuals, but it did in patients with clinically significant structural or functional heart problems. Lamotrigine can impede ventricular conduction (widen the QRS) and cause arrhythmia, which can result in sudden death. Elevated heart rates may potentially increase the likelihood of ventricular conduction slowing with lamotrigine. 
DOSAGE AND ADMINISTRATION:
The dosage depends on the patient's age, indication, and concurrent drugs. To minimize an increased risk of rash, do not exceed the recommended initial dose or future dose escalations. Do not reintroduce lamotrigine pills in patients who have quit owing to rash unless the potential benefits clearly exceed the dangers. Most patients who begin or discontinue estrogen-containing oral contraception will require adjustments to their maintenance doses. 
Lamotrigine is available as tablets, chewable tablets, extended-release tablets, and oral disintegrating tablets.

• Tablets - 25 mg, 100 mg, 150 mg and 200 mg.
• Chewable dispersible tablets - 2 mg, 5 mg, and 25 mg.
• Orally disintegrating tablets -25 mg, 50 mg, 100 mg, and 200 mg.
• Extended release tablets -25 mg, 50 mg, 100 mg, 200 mg, 250 mg, and 300 mg.

CONTRAINDICATIONS:

The major contraindication for administering lamotrigine is hypersensitivity to the drug or its components.

DRUG INTERACTIONS:

Dofetilide can interact severely with lamotrigine, hence the combination is highly advised against. Valproic acid, rifampin, estrogen-containing contraceptives, estrogen replacement therapy pharmaceuticals, and some barbiturates are among the other drugs that may cause significant interactions.

SIDE EFFECTS:

Common side effects of lamotrigine

• Constipation
• Blurred or double vision
• Fever
• Dizziness
• Headache
• Rash
• Insomnia
• Depression
• Tiredness
• Increase in seizures
• cough

Severe side effects of lamotrigine

• Dryness of the mouth
• Increase heart rate
• Drowsiness
• Clumsiness
• Loss of consciousness

TOXICITY:

Excessive lamotrigine overdoses, some as high as 16 g, have resulted in deaths from consequences such as seizures, coma, and conduction problems. Immediate-release lamotrigine is rapidly absorbed; therefore, producing emesis may not be the best solution in this case. Hospitalization and supportive treatment are recommended, as are the standard airway protection measures. As of this writing, there is no known particular antidote to lamotrigine poisoning.