indication

For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression.

pharmacology

Lamotrigine, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamotrigine is also used in the treatment of depression and bipolar disorder. Lamotrigine is thought to exert its anticonvulsant effect by stabilizing presynaptic neuronal membranes. Lamotrigine inhibits sodium currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excilatory amino acid, glutamate.

mechanism of action

One proposed mechanism of action of Lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. in vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels and/or calcium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Studies on lamotrigine show binding to sodium channels similar to local anesthetics.

toxicity

LD₅₀=250 (mg/kg) (in rat, mice); LD₅₀>640 orally (mg/kg) (in rat, mice) (Sawyer). Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs.

biotransformation

Hepatic

absorption

98%

half life

25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)

drug interactions

Butabarbital: Barbiturates like butabarbital may decrease the serum concentration of lamotrigine. There are separate patient management guidelines for patients age 12 and under and for patients older than 12 years of age. Monitor for decreased serum concentrations/therapeutic effects of lamotrigine if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.

Butalbital: Barbiturates such as butalbital may decrease the serum concentration of lamotrigine. There are separate management guidelines for patients age 12 and under and for patients older than 12 years of age. Please refer to the current approved prescribing information for additional information. Monitor for decreased serum concentrations/therapeutic effects of lamotrigine if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.

Carbamazepine: Lamotrigine may increase the adverse effects of carbamazepine by increasing the concentration of its active metabolite, carbamazepine-epoxide. Carbamazepine may decrease the therapeutic effect of lamotrigine by increasing its metabolism. Lamotrigine doses should be adjusted accordingly. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinue or doses are changed.

Clozapine: Lamotrigine increases the effect and toxicity of clozapine

Desogestrel: The oral contraceptive decreases the effect of lamotrigine

Ethinyl Estradiol: The oral contraceptive decreases the effect of lamotrigine

Ethotoin: Phenytoin may reduce levels of lamotrigine

Fosphenytoin: Phenytoin may reduce levels of lamotrigine

Mephenytoin: Phenytoin may reduce levels of lamotrigine

Mestranol: The oral contraceptive decreases the effect of lamotrigine

Methsuximide: Methsuximide decreases the effect of lamotrigine

Norethindrone: The oral contraceptive decreases the effect of lamotrigine

Phenytoin: Phenytoin may reduce levels of lamotrigine

Rifampin: Rifampin decreases levels of lamotrigine

Thiopental: Thiopental may increase the metabolism and clearance of Lamotrigine. Monitor for decreased therapeutic effect of Lamotrigine if Thiopental is initiated.

Triprolidine: The CNS depressants, Triprolidine and Lamotrigine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Valproic Acid: Valproic acid may increase the adverse effects of Lamotrigine by increasing Lamotrigine serum concentration. The Lamotrigine dose should be reduced by 50% during concomitant therapy. Monitor for changes in Lamotrigine therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed.