THURSDAY, Aug. 16, 2001 (HealthDayNews) -- In the third recall this year, the maker of one of the most popular brands of estrogen replacement therapy said late yesterday that more than 10 million pills are being pulled off wholesalers' shelves.
Add that to recalls in January and April, and the total number of Premarin pills taken off the market is more than 500 million doses.
Premarin, made by American Home Products, is apparently shy of meeting Food and Drug Administration (FDA) standards in regard to dissolution -- which is the criteria that measures how uniformly or evenly a drug dissolves in your body. If it dissolves too quickly or too slowly, your body won't get the correct dose of the medicine.
Premarin, derived from purified horse urine, is taken by 10 million women every day.
"Premarin, while it's been well studied, and it's been a good drug over the years, comes from horses' urine -- and because it is animal based, we don't know exactly what's in it other than the main ingredient, and you can't tell the horses what to pee," says Dr. Alan Altman, assistant clinical professor of obstetrics and gynecology and reproductive biology at Harvard Medical School .
As a result, says Altman, each time Wyeth-Ayerst, the manufacturer, makes Premarin, it's a little bit different from the time before, so, "sometimes a woman gets too much [estrogen], sometimes too little, and sometimes the right amount."
Other hormone replacement products, such as plant-derived Cenestin, a synthetic estrogen made by Cincinnati, Ohio-based Duramed Pharmaceuticals, Inc., don't have that problem, says Altman, because each and every pill is structurally identical.
Because new drug manufacturing technologies allow for better-controlled dissolution, older drugs like Premarin -- on the market for more than 58 years -- can find it difficult to meet current standards. Which is one reason they can be recalled.
"The [government] specifications [for dissolution] were amended in May 1998 and [some] Premarin manufactured after May has not met the new specifications. It's important to note that the product didn't change -- the specifications changed," says Audrey Ashby, spokeswoman for Wyeth, the division of American Home Products that makes and distributes Premarin.
And, in fact, even if formulations do differ from batch to batch, not all medical experts see it as a problem.
"Generally, the variations remain within such a strict level of acceptance, the difference from batch to batch is so small it's not really an issue," says Dr. Rogerio Lobo, chief of OB/Gyn at Columbia-Presbyterian Medical Center in New York City.
When a batch does exceed the normal acceptable levels, says Lobo, it is unlikely to reach the consumer.
"I believe any woman who is currently taking Premarin should feel extremely confidant in continuing to take it without hesitation. This is a quality control issue not a medical issue, and I don't think these recalls represent any major health or medical problems," says Lobo.
No one has reported any ill effects from taking any of the recalled drug.
The current recall, which was done at the wholesale level, involves one lot of 896 bottles and one lot of 1,174 bottles. Each bottle contains 5,000 tablets. The grand total of pills pulled off wholesalers' shelves: a whopping 10 million-plus pills, all in the dosage strength of 1.25 milligrams, a mid-strength dose of the five the company makes.
This current recall follows two others -- one in January, and a second in April of 2001 -- all for the same dissolution issue. According to FDA reports, more than 100,000 bottles of 5,000 pills -- a total of some 500 million doses of Premarin -- have been voluntarily recalled at the wholesale level, for dissolution problems since the start of this year.
While the focus of the current recall is wholesalers, some of the now-recalled pills could be sitting on the consumer's bathroom shelf. Indeed, because the dissolution problems were discovered in batches of older pills -- stashes routinely held by drug manufacturers in the event that safety testing becomes necessary -- the company has no way of knowing how many of the previously shipped pills from the same batch made it to the drugstore, and ultimately into women's hands.
Still, they insist there is no need for worry or alarm
"Women should be reassured that the product they have is not subject to the recall, and even if they have Premarin tablets from these lots, they contain the proper estrogen dose and will provide them with all the proven benefits," says Ashby. The company has declined to release lot numbers, saying only that the products consumers have are safe and do not need to be returned.
Premarin is is used primarily to treat symptoms of menopause including hot flashes and night sweats. It is also approved for the prevention of osteoporosis, a bone-thinning disorder related to a lack of estrogen.
Although it has been sold since 1942 without a patent, there is no generic version of the drug. The reason, says Altman, is that nobody really knows what's in it.
"Even the people who make Premarin don't know exactly what's in the formula," he says.
Indeed, in 1997 the FDA declared "the active ingredients of Premarin cannot be definitively identifiedÂ…[so] a generic version cannot be approved."
Manufactured from what American Home Products call a "complex blend of natural estrogens," which includes urine taken from pregnant mares, Premarin has also become a rallying point for animal rights activists.
What To Do
To learn more about natural alternatives to hormone replacement therapy, visit The North American Menopause Society, found here.
To learn more about the symptoms of menopause and the variety of drugs available for hormone replacement therapy, visit The National Institute on Aging found here.
