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Adverse effects of lacosamide are dose-dependent

NEW YORK (Reuters Health) – Pooled data on adverse effects of the anticonvulsant lacosamide show them to be dose-related, Italian and Canadian researchers say.

The effects were largely vestibulocerebellar – e.g., dizziness, ataxia, diplopia — and “clearly influenced by dose,” Dr. Gaetano Zaccara, who led the team, told Reuters Health by email.

In 2008, lacosamide (Vimpat) was approved in Europe and the U.S. as adjunctive treatment for partial-onset seizures, at doses of 200 or 400 mg per day.

To characterize the adverse effects, Dr. Zaccara of the University of Chieta and colleagues examined data from 10 randomized controlled trials of lacosamide involving more than 3,100 patients. Three trials focused on patients with pharmacoresistant epilepsy, four on neuropathic pain, one on migraine, one on fibromyalgia, and one on knee osteoarthritis. The trials lasted from 12 to 18 weeks.

No serious adverse events were associated with treatment, the researchers reported online July 10 in Epilepsia

Of 21 identified potential adverse events, 11 (52%) were significantly associated with lacosamide. The number of events increased with increasing dose.

At 200 mg per day, the only such event identified was dizziness. At 400 mg, in addition, vertigo, abnormal coordination, abnormal vision, nausea, and vomiting were experienced. At 600 mg – a dose not approved by European or American regulators — adverse events were dizziness, vertigo, ataxia, balance disorder, diplopia, fatigue, nausea, vomiting, and tremor.

Study withdrawals because of intolerable adverse events were significantly more common in patients taking the two higher doses. They were also significantly more frequent in the 600-mg group than in those given lower doses.

Adverse events tended to occur more frequently in patients with drug-resistant epilepsy. “The adverse effect profile of this drug,” added Dr. Zaccara, “seems to be influenced by concomitant diseases. It is possible that this depends on the associated drugs.” In particular, lacosamide might interact with other antiepileptic drugs.

Although formal cognitive testing was not performed in any of these trials, one apparent advantage, Dr. Zaccara pointed out, is the apparent “lack of sedative properties or cognitive effects.”

Although no comparisons were made with other antiepileptic drugs, Dr. Zaccara noted that “some adverse effects are more frequent with lacosamide… for example dizziness, while other adverse effects seem to be less frequent — for example, somnolence.”

So in a given patient, he added, one should consider the tolerability profile. “For example, if I have a patient with ataxia, perhaps it would be better to avoid lacosamide. For a patient more prone to somnolence, it might be OK.”

SOURCE: http://bit.ly/T6ChJY

Epilepsia 2012.