Migraine, Epilepsy Drug Topamax May Cause Newborn Cleft Palate

Editor's Choice
Main Category: Cleft Palate
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 04 Mar 2011 - 10:00 PDT


The FDA has warned that the drug prescribed for epilepsy named Topamax (topiramate) should not be used by women who are pregnant or plan on childbearing, due to a very high risk of offspring bearing cleft lip and palate defects occuring during the first trimester.

Topiramate treats epilepsy in children and adults and was originally marketed as an anticonvulsant. In children it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is also Food and Drug Administration approved for, and most frequently prescribed for, the prevention of migraines.

Psychiatrists have used topiramate to treat bipolar disorder, and often use topiramate to augment psychotrophics or counteract weight gain associated with numerous antidepressants.

Russell Katz, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research comments:

"Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age. Alternative medications that have a lower risk of birth defects should be considered."

Cleft lip and cleft palate, collectively called oral clefts, are birth defects that occur when parts of the lip or palate do not completely fuse together early in the first trimester of pregnancy, a time when many women do not know they are pregnant. The defects range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking, and to ear infections. Surgery often is performed to close the lip and palate and most children do well after treatment.

Based on the data, topiramate will have a stronger warning in its prescribing information (labeling). The pregnancy category will be changed to Pregnancy Category D. This means that there is positive evidence of human fetal risk based on human data, but the potential benefits of the drug in pregnant women may outweigh the risks in certain situations.

The Food and Drug Administration has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage, and may reverse the visual impairment.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations. This might be particularly important for women who take topiramate to prevent migraine attacks.

Topiramate has been associated with a statistically significant increase in suicidality.

It is possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores has been proposed as a mechanism.

Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.

Source: U.S. Food and Drug Administration

Written by Sy Kraft, B.A.


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