The Food and Drug Administration warned Friday that the use by pregnant women of a commonly prescribed class of drugs to treat high blood pressure can seriously harm or even kill a developing fetus.
The agency decided not to ban the class of drugs because it is valuable for many patients, while its risks are unique to pregnant women, said FDA Commissioner David A. Kessler.
"It's important that the drug be available to the general population, but we have a special obligation to warn those who could be injured," he said.
At the FDA's request, the six pharmaceutical companies that manufacture the 13 drugs in the class will alert physicians by letter that use of so-called angiotensin converting enzyme inhibitors, or ACE inhibitors, during the second or third trimester of pregnancy can result in face, skull and limb deformities, lung problems, kidney failure and even fetal death.
An estimated 6 million Americans take ACE inhibitors. Of these, about 5% are women under the age of 40, according to Merck & Co. Inc., which makes five of the drugs. The company also said 5.5 million women in the United States from 18 to 44 years old suffer from high blood pressure.
It estimated that 23 million individuals worldwide take ACE inhibitors, making them second in use to calcium channel blockers, another class of hypertension medications. ACE inhibitors work by interrupting a chemical chain reaction in the body that causes blood pressure to rise.
An estimated 10% of pregnant women develop high blood pressure during pregnancy. If untreated, the condition can lead to serious complications, including premature delivery and low birth weight. Thus, the FDA said, it is important that pregnant women with hypertension seek an alternative therapy if they are taking ACE inhibitors.
"ACE inhibitors should be discontinued as soon as possible when pregnancy is detected, and patients given these drugs should be made aware of the need to see their physicians should they become pregnant," the letter to physicians says.
The agency stressed that women who become pregnant while taking an ACE inhibitor should not stop treatment on their own, because "uncontrolled hypertension is dangerous to them and their fetuses."
Labeling for the drugs has warned of the risks since 1989, but more instances of fetal harm continue to be reported, including more than 50 clear-cut cases caused by the drugs in recent years, the FDA said.
These continued reports of injury have prompted stronger warnings. The companies have agreed to include a prominent "boxed" warning in the package insert, and the FDA has asked pharmacists nationwide to place a sticker directly on the prescription bottle urging women to consult a doctor promptly about switching to a different drug if they become pregnant.
"The additional warnings will allow the safe use of ACE inhibitors by women who need them while helping to assure that women who become pregnant while taking these drugs promptly seek alternative treatment," Kessler said.
The FDA said the drugs appear to be safe during the first trimester of pregnancy because the kidneys of the fetus are undeveloped. However, in later stages of pregnancy--when the fetal kidneys are working--the drugs impair their function, causing a reduction of the amniotic fluid surrounding the fetus. This can cause kidney failure, facial and skull deformities, and fetal lung problems, the agency said.
Merck manufactures Vasotec, Vasotec IV, Prinivil, Prinzide and Vaseretic. The other companies and their products are Capoten, Capozide and Monopril, made by Bristol-Myers Squibb Co.; Lotensin, made by Ciba-Geigy Corp.; Altace, made by Hoeschst-Roussel Pharmaceuticals Inc.; Zestril and Zestoretic, made by ICI Pharmaceuticals Group; and Accupril, made by Parke-Davis, a division of Warner-Lambert Co.