In 2009 the U.S. FDA (Federal Drug Administration) approved the use of lacosamide (Vimpat) for adjunctive therapy for partial-onset seizures in patients 17 years of age and older. Moreover, it approved an intravenous (IV) version of the drug when oral administration is not feasible in these same patients. It does not have an approval for its use in status epilepticus, seizure clusters or seizure emergencies. Since that time, lacosamide has rapidly ascended the prescription drug market as a popular choice of medication for epilepsy. In this month’s column we explore lacosamide (Vimpat) further.

Mechanisms

Similar to almost every other seizure medication currently approved, the mechanism of the antiseizure effect of lacosamide is not fully understood. It is believed that lacosamide impacts its antiseizure effect by enhancing sodium channel slow inactivation. Thus, lacosamide would have a similar yet distinct mechanism to other seizure medications, such as phenytoin, or carbamazepine.

Pharmacokinetics

Peak serum levels of the drug are reached one to five hours after oral administration and at the end of an IV dose. Food does not alter the rate or extent of Vimpat absorption. A 200 mg oral version of the medication is equal to IV versions of medications given over 30 to 60 minutes. Increasing lacosamide from 100 to 800 mg dose, results in a proportional increase in the serum level of the drug in one’s system. The half life of lacosamide is approximately 13 hours. Serum concentrations are reached after three days of twice daily dosing. The drug is eliminated by the kidney.

Lacosamide levels increase in patients with mild or moderate kidney disease and in patients with severe kidney disease, one need to adjust the dose appropriately. In patients with liver disease, Vimpat levels may increase from 50 to 60% and therefore doses should be adjusted downward for individuals with mild or moderate liver disease. In patients age 65 years and older there may be a slight increase in levels by 20% compared to younger patients, this means that lower doses of the medication are needed as compared to a younger aged adult.

Effectiveness

The effectiveness of lacosamide was established in three 12-week randomized, double-blind, multi-center studied enrolling adult patients. Patients enrolled in these studies exclusively had partial-onset seizures with or without spread that were not adequately controlled on one to three other antiepileptic drugs. The patient that would typically enroll in these trials tended to have somewhat severe epilepsy, with an average of four or more partial-onset seizures every 28 days, and no seizure-free period exceeding more than 21 days. The studies found that at its best, the median percentage reduction of seizure frequency was 35%; 37.3%; and 39% in the 3 studies. Fifty percent (50%) reduction in seizure frequency was achieved in 33%-35% who received 200 mg of the pill; 38.3%-41% with those taking 400 mg. Although lacosamide was tested at doses higher than 400 mg, the FDA approved the drug up to a dose of 400 mg, due to the fact that higher doses produced more side effects than benefits.

IV lacosamide was also trialed in a randomized, double-blind study with 60 patients. The IV version of the drug was consistent with the oral drug (drug taken by mouth) and seizure rates were similar to what was observed with the oral form. The drug was infused over 30 minutes in 40 patients; 50 minutes in 100 patients; and 10 minute in 20 patients. Adverse reactions did not differ with varying administration times; however, the drug was approved to a maximum drug infusion of 300 mg over 30-60 minutes.

Side Effects

Lacosamide’s most common adverse effects include dizziness, ataxia or syncope. Dizziness occurred in 25% of patients receiving lacosamide as add-on therapy. Ataxia, or gait disturbance, was experienced by 6% who were receiving lacosamide. Dizziness and ataxia were observed while the drug was being initiated. Episodes of syncope were reported in individuals with diabetic neuropathy. There also appears to be no clear abnormalities related to psychiatric, mood or behavioral issues related to use of the medications. There is a small but measurable cardiac effect with the use of lacosamide. A dose-dependent PR interval prolongation has been observed in association with lacosamide. Caution is advised for patients who have a known cardiac conduction problem, such as first degree AV block, second degree or higher AV block, or sick sinus syndrome without a pacemaker. Patients with myocardial disease or heart failure and patients taking other drugs known to impact PR interval should obtain an EKG while taking this drug.

Lacosamide is considered a pregnancy category C drug. This means that effects on the developing baby has not been observed in humans, however, this effect was seen in rats. Lacosamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether lacosamide is found in human milk. Thus, lacosamide should not be used in mothers who are breastfeeding.

Drug Interactions

Lacosamide does not have any drug interactions associated with the use of other seizure medications. It does also not have any interactions with oral contraceptives (birth control pills), heart drugs, blood pressure drugs, or antibiotics.

Dosing

Lacosamide therapy can be started orally at an initial dose of 50 mg twice daily. This can be increased based on tolerability by up to 100 mg per day in two divided doses on a daily basis. It is important to note that with lacosamide, the faster that one increases the dose of the drug the more likely one is to encounter side effects. This is important in older adults and other individuals who are sensitive to medication. Thus the adage of going “slow and low” when dosing the older adults is vital in order to maximize tolerability.

Lacosamide can be taken with or without food. Its maximum dosage should be 400 mg, although higher than 400 mg can be used if the physician feels that the benefits of the increased dose outweigh the risks of side effects.

Summary

Lacosamide is a unique medication for individuals with uncontrolled partial seizures. Its primary advantages include the fact that it has no drug interactions, is dosed twice a day, and it effective. The drug appears to work in a manner similar yet distinct to phenytoin and carbamazepine. The drug has an IV formulation, therefore it might be useful in emergency situations; but again, it has not been approved for use in this condition.

How Can Epilepsy Therapy Project Help

The Epilepsy Therapy Project is committed to advancing novel epilepsy treatment to get them to the patient with epilepsy as safely as feasible within the current system. By focusing on new medications it is able to hopefully improve the quality of life of patients with epilepsy. By the use of My Seizure Diary on epilepsy.com it is able to help patients proceed with self-management technique that might improve the quality of life. The Epilepsy Therapy Project is committed to education and research in epilepsy and hopes to bring information such as this column to both physicians and individuals with epilepsy alike so they may benefit from potentially helpful treatment, such as lacosamide.