Neurology Journal: Johnson & Johnson's Drug Topamax May Increase Risk of Birth Defects

Beware If Taking This Seizure Medicine Alone Or With Other Epilepsy Drugs During Pregnancy

(Posted by Tom Lamb at DrugInjuryWatch.com)

The July 22, 2008 issue of Neurology, the medical journal of the American Academy of Neurology (AAN), includes an article which reports taking the epilepsy drug Topamax (topiramate) alone or along with other epilepsy drugs during pregnancy may increase the risk of birth defects. 

This Neurology study, "Topiramate in pregnancy -- Preliminary experience from the UK Epilepsy and Pregnancy Register", reports that exposure to the antiepileptic medicine Topamax in the first trimester of pregnancy carries a higher-than-usual rate of congenital malformations.  Researchers prospectively followed some 200 women with epilepsy who became pregnant while taking Topamax, either alone or with other antiepileptic drugs.

According to a July 15, 2008 AAN press release, "Epilepsy Drug May Increase Risk of Birth Defects":

For the study, researchers examined women who became pregnant while taking topiramate either on its own or along with other epilepsy drugs. Of 178 babies born, 16 had major birth defects. Three of these were in infants whose mothers were taking only topiramate, and 13 were in those whose mothers were taking topiramate and other epilepsy drugs....

“More research needs to be done to confirm these results, especially since it was a small study,” said John Craig, MRCP, of the Royal Group of Hospitals in Belfast, Northern Ireland. “But these results should also get the attention of women with migraine and their doctors, since topiramate is also used for preventing migraine, which is an even more common condition that also occurs frequently in women of childbearing age.”

Craig said the risk of birth defects may be different for women taking the drug for migraine, but that the pregnancies of women exposed to topiramate should be monitored.

From a July 21, 2008 Bloomberg news article, "J&J's Topamax Raised Birth Defect in Epilepsy Study (Correct)", we get this additional insight:

In a study of 203 pregnancies, the rate of children born with cleft palates or cleft lips was 11 times higher among women taking Topamax alone or with other drugs than in the general population. A genital defect in boys [hypospadias] was 14 times higher than normal, the U.K. researchers found....

"You can't take the results for definite because of the small sample size and the wide confidence intervals," said Stephen Hunt from the U.K.'s Epilepsy and Pregnancy Register, in an interview.  "It's notable that we've observed an increased number of cleft lips and hypospadias for monotherapy, which we've also seen in animal studies and post-marketing studies in humans."

The major defects when Topamax was taken alone were two cleft lips and one case of hypospadias, where the opening to the urinary tract is not located at the tip of a boy's penis....

Topamax used alone led to three major congenital malformations and five minor birth defects. It resulted in 13 major and 10 minor malformations in combination with other epilepsy therapies including Sanofi-Aventis' Frisium, Sabril, Epilim or Depakine, Pfizer Inc.'s Zarontin, UCB SA's Keppra as well as generic drugs carbamazepine, phenobarbitral or phenytoin.

More birth defects occurred in women taking Topamax along with the drug valproate, or valproic acid, than in women taking Topamax and another epilepsy drug, Hunt found. Valproate is sold as Depakote by Abbott Laboratories and as Depakine by Sanofi-Aventis.

Previous research has shown that valproate is associated with an increased risk of birth defects such as heart defects and spina bifida.

Topamax has been assigned a pregnancy Category C classification by the FDA.  Generally, drugs in Category C have not been studied in pregnant women but drugs in this category appear to cause harm to the fetus in animal studies.  According to Johnson & Johnson's current package insert, or label, for Topamax, this particular epilepsy drug has been associated with birth defects, miscarriages, and decreased fetal weight in rabbits, rats, and mice.

Although it has been known some other drugs to treat epilepsy can increase the chance of miscarriage and birth defects, women suffering from epilepsy need to take these drugs in an attempt to prevent seizures that can harm the fetus.