Rufinamide

RUFINAMIDE

Rufinamide is a triazole derivative with little similarity to other antiseizure drugs.

Mechanism of Action

Rufinamide is protective in the maximal electroshock and penty-lenetetrazol tests in rats and mice. It decreases sustained high-frequency firing of neurons in vitro and is thought to prolong the inactive state of the Na⁺ channel. Significant interactions with GABA systems or metabotropic glutamate receptors have not been seen.

Clinical Uses

Rufinamide is approved in the USA for adjunctive treatment of sei-zures associated with the Lennox-Gastaut syndrome in patients age 4 years and older. The drug is effective against all seizure types in this syndrome and specifically against tonic-atonic seizures. Recent data also suggest it may be effective against partial seizures. Treatment in children is typically started at 10 mg/kg/d in two equally divided doses and gradually increased to 45 mg/kg/d or 3200 mg/d, which-ever is lower. Adults can begin with 400–800 mg/d in two equally divided doses up to a maximum of 3200 mg/d as tolerated. The drug should be given with food. The most common adverse events are somnolence, vomiting, pyrexia, and diarrhea.

Pharmacokinetics

Rufinamide is well absorbed, but plasma concentrations peak between 4 and 6 hours. The half-life is 6–10 hours, and minimal plasma protein binding is observed. Although cytochrome P450 enzymes are not involved, the drug is extensively metabolized to inactive products. Most of the drug is excreted in the urine; an acid metabolite accounts for about two thirds of the dose. In one study, rufinamide did not appear to significantly affect the plasma concentrations of other drugs used for the Lennox-Gastaut syn-drome such as topiramate, lamotrigine, or valproic acid, but con-flicting data suggest more robust interactions with other AEDs, including effects on rufinamide levels, especially in children.