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Hundreds of Unapproved Drugs Sold By Prescription

Posted on: Monday, 18 September 2006, 06:00 CDT

By Rita Rubin

They have official-sounding names, like Lodrane XR Suspension and Cortane B.

They're listed in the Physician's Desk Reference and advertised in medical journals.

You can buy them in drugstores, in person or online, but only if you have a doctor's prescription. They even have generic competitors.

Yet, what looks like a Food and Drug Administration-approved drug and sounds like an FDA-approved drug might not really be an FDA-approved drug. And that little-known fact means consumers -- not to mention doctors and pharmacists, who are often as ignorant of the drugs' status as patients are -- should beware, the FDA says.

Unapproved drugs, which, the FDA says, make up nearly 2% of all prescription drugs on the market, might not only be ineffective but also might actually be harmful. Over the years, the agency has learned of dozens of deaths linked to some of them. For now, the FDA says, it is targeting only the most dangerous because it lacks the resources to get all of them off the market.

The agency estimates that several hundred unapproved active ingredients, including antihistamines, narcotics and sedatives, are in prescription drugs sold in the USA. Many of them have been used since before 1962, when an amendment to the Food, Drug, and Cosmetic Act required that drugs be proven effective. (The original law, enacted in 1938, said only that drugs had to be proved safe.)

Those several hundred unapproved active ingredients translate into a couple of thousand unapproved prescription products or more. They're marketed for a range of ailments: colds and coughs, ear infections, hot flashes and pain. But their makers never submitted scientific data that convinced the FDA of their safety and effectiveness.

"We have concerns about their safety, about their quality, about their labeling," says Deborah Autor, the FDA's director of compliance. "Just because people think something works doesn't necessarily mean that it does."

The 'time-tested' standard

In their defense, makers of unapproved prescription drugs say the medications must be safe and effective or else doctors wouldn't keep prescribing them. The companies say wading through the FDA's regulatory process would cost millions of dollars, an expense they'd have to pass on to consumers.

"Quality products at a price the patient can afford" is the motto of one such company, ECR Pharmaceuticals of Richmond, Va., maker of Bupap headache reliever and other unapproved prescription products. CEO E. Claiborne Robins Jr. is the great-grandson of Alfred Hartley Robins, whose 19th-century apothecary grew into giant drugmaker A.H. Robins. Robins was CEO of A.H. Robins when it was sold to American Home Products, later Wyeth, in 1989.

If Pharmics Inc. had to get FDA approval, CEO Paul Bagley says, it "would put us out of business." He says his Salt Lake City company sells only $500,000 worth of products a year, such as prescription O-Cal Prenatal vitamins.

"'Unapproved' sounds horrible," Bagley says. "A lot of these products have been on the market for 50 years. ... They've been time-tested better than a lot of the new products approved by the FDA."

That's not good enough, says Kenneth Kaitin, head of the Tufts Center for the Study of Drug Development in Boston: "I want a product the FDA has authorized. The FDA is not infallible, but it's the best thing we've got for ensuring the quality of our drug supply."

Blansett Pharmaceuticals' website implies that its unapproved products, such as Cortane B ear drops, are of higher quality than approved versions. The Little Rock company's strategy is "to reformulate existing pharmaceutical products for the purpose of improving safety, efficacy and patient compliance," its website says.

Just because an unapproved prescription drug has the same ingredient as an approved drug doesn't mean it's safe and effective, Kaitin says. A single ingredient at a certain dose might be, but add another ingredient or double the dose, he says, "and you've got an unapproved drug."

And, Kaitin says, even if the ingredients are identical to an approved product's, consumers can't trust they're effective without the FDA checking whether a long-acting pill really works for 24 hours or whether a drug can stand up to medicine chest humidity.

FDA has to pick its battles

Why doesn't the FDA just pull all unapproved drugs off the market? "It's a resource-intensive process," so the agency must focus on potentially dangerous drugs, Autor says.

Most recently, the FDA cracked down on unapproved products containing the antihistamine carbinoxamine. In June, the agency told their makers to seek approval or stop production by Sept. 7. FDA spokeswoman Susan Cruzan said Friday that all of the manufacturers had agreed to comply.

The FDA had received reports linking unapproved carbinoxamine products to 21 deaths of children under age 2. Labeling for the two approved products, Palgic and Carbinox Maleate, both made by Mikart, Inc., of Atlanta, says they're not to be used in children under 2.

Last winter, two infants died in Kane County, Ill., after ingesting Carbaxefed RF drops prescribed by their pediatricians, says Loren Carrera, chief deputy coroner. The drops contained carbinoxamine, pseudoephedrine, a decongestant, and dextromethorphan, a cough suppressant.

Chang Lee, vice president for clinical research at Morton Grove Pharmaceuticals in Illinois, said last week that his company stopped making Carbaxefed DM RF drops in January and that the company had "no knowledge" of the infants' deaths.

The coroner ruled the deaths accidental as a result of intoxication by pseudoephedrine and dextromethorphan. "The prescription was written correctly for the size and age of the child," but the families gave too big a dose, Carrera says. As the FDA's Autor notes, though, correct doses for unapproved drugs aren't known, because the necessary studies haven't been done.

Richard Foster, head of marketing for URL/Mutual Pharmaceuticals of Philadelphia, says unapproved quinine sulfate products, used to treat malaria, contain one-half to double the dose found in his company's Qualaquin, the only approved quinine sulfate drug.

Too little of any drug could be ineffective, while too much could be dangerous. Quinine sulfate can cause abnormalities in the heart's electrical system that can, in rare instances, lead to potentially fatal irregular heartbeats. The higher the dose, the greater the risk.

Qualaquin's label mentions the heart risk, but the unapproved products' labels do not, says Mutual CEO Richard Roberts, adding that over the years, the FDA has received reports of 23 deaths linked to those drugs.

Roberts says his company sold an unapproved quinine sulfate product "for years" but decided to seek FDA approval to corner the market. Because quinine sulfate is potentially dangerous, Roberts says, his company assumed the FDA would ban unapproved products once an approved version became available.

The FDA approved 324-milligram Qualaquin capsules in August 2005. But Mutual, waiting for the FDA to ban unapproved competitors, did not launch its drug until July. "We just felt we couldn't wait anymore," Roberts said. "We've invested millions of dollars in researching this product and going through the regulatory process. ... So far it's only been a financial loss for us."

Roberts says most pharmacists don't realize that some drugs they dispense are unapproved. In July, his company commissioned a nationwide survey of 500 pharmacists. It found that 91% of them thought all of the products they dispense are FDA-approved.

Mutual filed court motions in mid-August against the seven makers of unapproved quinine sulfate. So far, Roberts says, all but one have agreed to stop selling their products by Nov. 15. He says the only holdout is Teva Pharmaceuticals, which sells Quinamm. In an e-mail, spokeswoman Denise Bradley said Teva could not comment "in light of the pending litigation."

Roberts says his company was inspired to seek FDA approval by Adams Respiratory Therapeutics, maker of over-the-counter Mucinex, an extended-release guaifenesin pill. The FDA approved Mucinex in July 2002 and then told makers of unapproved versions, all of which required a prescription, to stop selling their products by Dec. 1, 2003, which they did.

In May 2004, the FDA approved another version of the drug, Adams' Mucinex DM, a non-prescription extended-release product containing guaifenesin and dextromethorphan, but it has not yet banned unapproved versions, says Janet Barth of Adams, in Chester, N.J.

ECR Pharmaceuticals makes the prescription drug Nasatab LA (for long-acting), an unapproved competitor of OTC Mucinex D, launched in October. Both drugs contain guaifenesin and pseudoephedrine.

Taking Nasatab through the FDA regulatory process would cost up to $10 million, says Davis Caskey, ECR's managing director. And that, Caskey argues, would not be money well spent. "All of us are in business to make a living," he says. "The endpoint is we want to supply quality drugs for a reasonable price."

(c) Copyright 2005 USA TODAY, a division of Gannett Co. Inc.

Source: USA TODAY

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