July 3, 2018
The U.S. Food and Drug Administration is alerting veterinary medical professionals, as well as those who work with horses and pigs, that a synthetic progesterone product commonly used in these animals may cause reproductive system disorders and other adverse effects in people who become exposed to the drug. The FDA is providing this alert because of the nature of the adverse events, some of which have occurred in teenage girls.
Altrenogest belongs to the class of drugs called progestins and is used to suppress estrus (commonly called “heat” or “season”) in mares (female horses), and to synchronize estrus in gilts (young female pigs). It is marketed under several brand names, including the equine products Regumate, Ovamed and Altren; and the swine products Matrix, Chronomate and Swinemate. The equine products are available via a veterinarian’s prescription and can be administered directly on the base of the mare’s tongue or on the mare’s feed. The swine products are available over-the-counter and are administered on a portion of the gilt’s feed. These liquid products may be administered to the animals on a daily basis for prolonged periods of time.
The agency has received 130 reports of accidental human exposure to altrenogest products between October 6, 1987 and May 30, 2018; 121 of those were for Regumate, approved in 1983, and nine reports were for Matrix, approved in 2003. Although the FDA has not received any reports for the other (generic) products, the agency’s alert includes these products because they are used in the same manner as Regumate and Matrix and on the same animal populations, and therefore have the same risk for adverse events.
Some reports described exposures in more than one person. Adverse effects were reported in 137 people, including 115 women and 22 men. Eighteen of the women affected were teenage girls. Some reports have described adverse effects in girls as young as 14 years of age.
Most people became exposed when the drug contacted their skin. Some of these exposures have occurred when people, who did not administer the drug, touched product residue on barn surfaces, equipment, or treated animals.
Reproductive adverse effects reported in women and girls include abnormal or absent menstrual cycles, and in men include decreased libido. Other adverse effects reported after exposure include: headaches, fever, abdominal pain, nausea, diarrhea, vomiting and rashes.
The FDA is aware that adverse events may be under-reported, particularly if the effects are mild or the person is not aware they were exposed. Therefore, the true number of adverse events may be greater than reported.
The labeling for all altrenogest products includes extensive warnings against human exposure, as the hormone is readily absorbed through intact skin. Altrenogest is not approved for use in people; the following list of exposure precautions is based upon the known effects of other progestins used in people on a chronic (long-term) basis.
PEOPLE WHO SHOULD NOT HANDLE ALTRENOGEST PRODUCTS:
- Women who are or suspect they are pregnant.
- Anyone with thrombophlebitis or thromboembolic disorders or with a history of these events.
- Anyone with cerebral-vascular or coronary-artery disease.
- Women with known or suspected carcinoma of the breast.
- People with known or suspected estrogen-dependent neoplasia.
- Women with undiagnosed [unexplained] vaginal bleeding.
- People with benign or malignant tumors which developed during the use of oral contraceptives or other estrogen-containing products.
- Anyone with liver dysfunction or disease.
It is essential that people administering altrenogest products take appropriate precautions to prevent exposing themselves or other people to the medication. Product labeling directs the use of impermeable, non-porous protective gloves when handling these drug products. These gloves should be nitrile, butyl, vinyl, polyethylene or neoprene. Disposable latex gloves may not provide adequate protection when handling these drug products. If accidental exposure does occur, it is important to wash away any drug product on skin, eyes, mouth or clothing. If adverse effects become apparent, seek medical care.
Users should be vigilant to ensure that any equipment that comes into contact with the product, as well as any drug product spilled in work areas or on the outside of the container, are adequately cleaned and decontaminated to prevent human exposure. Syringes used for administration should be replaced frequently and disposed of in a secure manner to prevent exposure to the product. The FDA has approved dosing guns for use with Regumate and Matrix. The use of these dosing guns may reduce exposure to people administering these drug products. The dosing guns are specific to the drug products for which they are approved and are not interchangeable with any other drug products. Appropriate protective gloves should always be worn when assembling, disassembling or cleaning these dosing guns or any spilled drug product.
The FDA has been in contact with Merck, the sponsor (the company that owns the right to market the product) of the pioneer products Regumate and Matrix, to discuss ways that the labeling and packaging of these products could be modified to enhance safety to the user. Any changes to the labeling of these pioneer products must, by law, be applied to any generic products.
The agency has issued a Warning Letter to Bimeda, the sponsor of Ovamed, a generic altrenogest equine product, because an advertisement for the product did not include important risk information associated with use of this product. Omission of this information in promotional materials created a misleading impression about the safety of Ovamed for people handling and administering the product.
The FDA continues to monitor reports of adverse drug events in people exposed to altrenogest products. Veterinary professionals, horse owners, and operators and employees of swine and equine facilities are encouraged to report adverse drug events to product manufacturers, who in turn are required to report this information to the FDA.
Contact information to report adverse events to drug sponsors:
Equine products (altrenogest 2 mg/mL, Rx):
- Regumate, (approved 1983) NADA 131-310, Merck Animal Health, 800-211-3573
- Ovamed, (previously Altresyn, approved 2012) ANADA 200-481, Bimeda, Inc., 888-524-6332
- Altren, (approved 2017) ANADA 200-620, Aurora Pharmaceuticals, LLC, 888-215-1256
Swine products (altrenogest 2 mg/mL, OTC):
- Matrix, (approved 2003) NADA 141-222, Merck Animal Health, 800-211-3573
- Chronomate, (approved 2015) ANADA 200-579, Ceva Animal Health, LLC, 800-999-0297
- Swinemate, (approved 2017) ANADA 200-621, Aurora Pharmaceuticals, LLC, 888-215-1256
For additional information about adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or visit Safety & Health.
For questions, Contact CVM.