FDA Panel Rejects Black Box Warning On Epilepsy Drugs

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Main Category: Regulatory Affairs / Drug Approvals
Also Included In: Epilepsy;  Headache / Migraine;  Pharmacy / Pharmacist
Article Date: 14 Jul 2008 - 1:00 PDT

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A panel of experts that advises the US Food and Drug Administration (FDA) voted last week to reject the Agency's proposal to make manufacturers of 11 epilepsy drugs put the strongest level of warning label on their products (the Black Box warning). The FDA had recommended the Black Box warning because studies showed the drugs had nearly double the risk of suicide compared to placebo, although in absolute terms it was still quite small. The panel did however, recommend the warning should be increased, but not to the Black Box level.

The FDA had conducted a review of nearly 200 studies on anti-seizure drugs and concluded that they raised the risk of suicide compared to placebo.. But although the panel of 20 members voted unanimously in support of the findings, bar one abstention, the majority did not support the agency's recommendation that the drugs should carry the Black Box warning. Instead they voted in favour of sending doctors a medication guide describing the suicide risks, reported the Washington Post.

The committee was concerned that should the most severe level of warning be placed on the drugs, doctors would get over cautious and stop prescribing them for patients that really need them. FDA's Director of the Division of Neurology Products, Dr Russell Katz, told the Post in a teleconference that:

"The committee voted 14 'no, it should not be described in a box warning, although it should be described in the label somewhere.' There were four 'yes' votes and three abstentions."

The FDA is not required to follow the advice of its expert panels, although it usually does. Katz said the agency will now be discussing their advice.

"We take the committee's recommendations very seriously," he said.

Manufacturers appear to have welcomed the committee's decision. A representative from Pfizer, which makes Lyrica and Neurontin, two of the drugs included in the review, told WebMD that:

"Overwarning actually has the potential to negatively impact patient care."

Some say this is what happened in 2005 when the FDA put Black Box warnings on antidepressants after a similar review suggested some of them could increase suicidal behaviour. But critics said the stern warnings stopped patients who needed the drugs from taking them, and the agency later changes the warnings.

A member of the advisory committee, Dr Rochelle Caplan, professor of psychiatry at University of California Los Angeles, told WebMD:

"We have to be very careful about scaring the patients into not taking these drugs, and I think we have to be very thoughtful about that."

The 11 anti-seizure drugs included in the FDA review are:

1. Carbamazepine (Carbatrol. External link" target="_blank">CARBATROL, Shire Pharmaceuticals, EQUETRO, Validus Pharmaceuticals Inc, Tegretol (carbamazepine USP). External link" target="_blank">TEGRETOL, Tegretol XR, Novartis Pharmaceuticals Corp).
2. Felbamate (FELBATOL, Meda Pharmaceuticals Inc).
3. Gabapentin (NEURONTIN, Pfizer Inc).
4. Iamotrigine (Lamictal (lamotrigine) Chewable Dispersible Tablet. External link" target="_blank">LAMICTAL, GlaxoSmithKline).
5. Levetiracetam (Keppra. External link" target="_blank">KEPPRA, UCB Inc).
6. Oxcarbazepine (Trileptal (oxcarbazepine) Tablets. External link" target="_blank">TRILEPTAL, Novartis Pharmaceuticals Corp).
7. Pregabalin (LYRICA, Pfizer Inc).
8. Tiagabine (GABITRIL, Cephalon Inc).
9. Topiramate (Topamax. External link" target="_blank">TOPAMAX, Ortho-McNeil-Janssen Pharmaceuticals Inc).
10. Valproate (Depakote ER (divalproex sodium). External link" target="_blank">DEPAKOTE, DEPAKOTE ER, DEPAKENE, DEPACON, Abbott Laboratories).
11. Zonisamide (Zonegran (zonisamide) Capsules. External link" target="_blank">ZONEGRAN, Dainippon).

These antiseizure drugs are used to treat not only epilepsy but also migraines, bipolar disorder, and other conditions, said the FDA.

The agency urged patients not to change or stop their medication without consulting their doctor.

Sources: Washington Post, WebMD, MNT archives.

Written by: Catharine Paddock, PhD


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