Popular Drug for Constipation Poses Serious Risks to Pregnant Women; FDA Must Increase Warnings, Public Citizen Says

May 6, 2009

Popular Drug for Constipation Poses Serious Risks to Pregnant Women; FDA Must Increase Warnings, Public Citizen Says

Consumer Group Petitions Agency to Add ‘Black Box’ Warning to Lubiprostone

WASHINGTON, D.C. – The Food and Drug Administration (FDA) should immediately increase its warnings about the use of lubiprostone – available as Amitiza – because of serious adverse reactions, including the risk of abortion or premature labor if given to pregnant women, Public Citizen said in a petition filed today with the agency.

The warning labels on lubiprostone, which is prescribed for the treatment of chronic constipation in adults and irritable bowel syndrome in women, are completely inadequate, the petition says: Even in controlled clinical trials, where women were instructed to be on two methods of contraception, six women became pregnant.

Lubiprostone is in the same class as misoprostol (both are prostaglandin E1 analogs), a drug widely used off-label in medical abortions to induce uterine contractions. Studies submitted with lubiprostone’s original drug application showed that the drug caused a significant number of dose-related abortions in guinea pigs, the appropriate abortion model for humans. Unlike the deficient lubiprostone label, the current misoprostol label states, “CYTOTEC (MISOPROSTOL) ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH.”

The petition asks the FDA to require drug companies label lubiprostone with a “black box” warning, the strongest warning the agency can issue, and require that patients be given an FDA-approved medication guide with their prescription warning them of the possibility of abortion. The FDA also should require the manufacturer to send a warning letter directly to doctors alerting them to the dangers the drug poses to pregnant women and nursing mothers.

“The FDA and drug makers should take every step possible to warn pregnant women and their doctors about the dangers of taking lubiprostone. The current label is grossly inadequate as it lacks useful information pertaining to the risks of drug-induced abortion in pregnant women who take this drug,” said Sidney Wolfe, M.D., director of the Health Research Group at Public Citizen and as its acting president. “There are safer, equally effective, alternative medications for pregnant women.”

The FDA also should move lubiprostone from the “C” to “X” pregnancy category of drugs to alert women to the potential hazards to the fetus, the same category as misoprostol, Wolfe said. The FDA defines pregnancy category X as one that pregnant women should not use, as compared to C, which acknowledges risks but says the drug may be used during pregnancy if the potential benefits justifies the potential risk to the fetus.

In this case, the risk does not outweigh the small benefit (only a 6 percent difference in results for irritable bowel syndrome between the treated group and the group given the placebo during studies), Wolfe said.