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updated 3/11/2009 9:16:47 AM ET 2009-03-11T13:16:47

While going through menopause, Marcia Sticka developed miserable hot flashes and night sweats, dry skin, a short temper, and an uncharacteristic lack of energy. No more: Every day for the past three years, she's rubbed a low, precisely measured dose of the hormone testosterone onto her inner thighs, and she feels great.

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"It really helped the hot flashes and night sweats, I'm not cranky all the time, and I wake up raring to go," says Sticka, 57, of Hillsboro, Ore.

Sticka is one of millions of people benefiting from compounding — when pharmacists prepare drugs in doses, forms, and combinations not available from manufacturers. In this case, the standard prescription testosterone gel (Androgel) is suitable only for men, delivering several times the daily dose Sticka's doctor prescribed.

More than 30 million prescription drugs are compounded each year, and they're a godsend for people with needs that off-the-shelf pharmaceuticals can't meet. But these drugs have recently come under attack. Critics are concerned that some compounders are acting like drug manufacturers, doctors, or both — but without the same safeguards. There's good reason to be worried: Compounded drugs are blamed for a host of serious side effects, including three recent deaths. Even if this is the first you've heard of compounding, you shouldn't feel immune to its potentially negative consequences. As the practice becomes more widespread (over the past decade, it's burgeoned into at least a $5 billion business), it has the potential to affect millions.

Lifesaver or risky business?
All of the nearly 200,000 pharmacists in this country are licensed to compound, and about 5,000 make it a specialty. At their best, compounding pharmacists occupy a respected, time-honored position in the medical system. From modifying the strength of a medication to altering the form or flavor so it's easier to swallow, they fill a vital need if you can't take commercial, one-size-fits-all prescription drugs.

The problem is the changing nature of compounding. Traditionally, it involves a sacrosanct "triad relationship" between a patient with a special need (such as Sticka), a physician who writes her a prescription, and a pharmacist who tailors the drugs.

But lately some shady prescription drug manufacturers are calling themselves compounders to get around the FDA's stringent oversight of pharmaceuticals. Even some corner drugstore types — in an effort to drum up new business and boost profits — seem to be overstepping their bounds in a way that puts consumers at risk.

Compounding goes awry
Though compounders aren't supposed to make anything unless they receive a specific prescription, many are producing, stockpiling, and marketing large quantities of Rx drugs — creating what's being dubbed a "shadow drug industry." However, unlike drugs made by the pharmaceutical industry, compounded medicines aren't regulated by the FDA. This lack of oversight is accepted when pharmacists make drugs for a single patient. But these large-scale compounders often employ poor manufacturing processes that can result in products without the required strength, quality, or purity — meaning an error could endanger many.

This worst-case scenario happened to Margrit Long of Portland, Ore., who sought relief from chronic back pain. Her doctor suggested injections of colchicine, a drug used in pill form to treat gout, and prescribed off-label in injection form for back pain. The doctor got the medication from ApothéCure, a Dallas pharmacy that promotes its compounded injectables. The strong anti-inflammatory action of the shots seemed to help with Long's pain for several years — until March 2007, when an injection killed her. The problem: a measurement error by the person mixing the prescription, which meant that Long and at least two others were fatally injected with eight times the intended amount of colchicine. ApothéCure ultimately recalled more than 3,500 vials of the drug distributed nationwide.

Errors don't have to be reported
Precisely how many other compounding errors there are isn't known. That's because — unlike commercial drug manufacturers — pharmacies in most states aren't required to report adverse events associated with compounded drugs to the FDA or state pharmacy boards. But the one state that tests random samples of drugs has uncovered problems. When Missouri's board of pharmacy spot-checked compounded prescriptions in 2007, 51 of 213 prescriptions tested were more than 10 percent off in the dose of active ingredients, one had only one-fifth of the amount needed, and another had 4 1/2 times the prescribed dose.

Horror stories like Long's aren't the exclusive domain of large-scale compounders: Local compounding pharmacists can be overconfident in their ability to make what patients and physicians need. In 2001, Doc's Pharmacy in Walnut Creek, Calif., began compounding a steroid that the manufacturer had temporarily stopped making. But the reputable pharmacy was unable to create a sterile compound, and within a few months, three people treated with the contaminated injections died of meningitis. This outcome shouldn't be that surprising, considering that just 1 in 5 schools of pharmacy offers a special course on compounding sterile medications. Only 13 percent of pharmacy school deans felt that their students graduated with adequate training in compounding sterile preparations, according to a 2005 survey. Yet all pharmacists are licensed to compound.

Pharmacists as physicians?
Some compounders veer toward practicing medicine themselves, dispensing advice directly to customers on the best drug for their ills. This is especially true when it comes to "bioidenticals." These prescription hormones, frequently used to treat perimenopausal discomfort, are synthesized to be molecularly identical to specific human hormones. It's okay for compounders to make up prescriptions for various combinations of hormones, but compounders frequently promote bioidenticals as natural, risk free, and able to prevent or cure a host of medical conditions. The truth: Bioidenticals are created in a laboratory, often by manipulating plant hormones, and there's no proof they have fewer or different risks than other hormones or offer any specific health benefits.


But that's not what many hear. At some pharmacies, you can go to a lecture on the benefits of bioidenticals, schedule an individual consultation to review your symptoms, take hormone tests that the pharmacist analyzes, and have a customized bioidentical hormone prescription recommended and sent to your physician's office for a signature. If your doctor's not amenable, the pharmacy helps you find a physician who is.

Experts, including the FDA, strongly object to how bioidenticals are being promoted, especially because many of these same claims were made — and proven wrong — about commercial estrogen products. Indeed, in a 2001 study of 664 postmenopausal women, when the estradiol used in many compounded formulas was tested for its ability to prevent a repeat stroke, women who took the hormone had no fewer heart attacks or strokes — and their strokes were more severe and more often fatal. "Compounding can be a fine way to get low doses of hormone therapy. But hormones don't magically become safer because they're compounded — they just lose their warning labels," says Adriane Fugh-Berman, MD, an associate professor in the complementary and alternative medicine program at Georgetown University Medical Center.

‘I'd be dead without compounded drugs’
Negative publicity hasn't shaken Ottilie Ruh's confidence in compounding. After developing a severe corn allergy at 43, the Salem, Ore., woman became dependent on compounding (nearly all drugs contain corn as an inactive filler). It's more expensive to have her medications — antibiotics, steroids, and aspirin — made into corn-free formulations. But the extra cost is worth it, says Ruh, who insists, "I'd be dead without compounded drugs."

Testimonials like this are what make compounding so much more rewarding than traditional retail pharmacy, say practitioners. "There are bad eggs in every industry, but ours as a whole is a very caring profession," says Dana Reed-Kane, PharmD, co-owner of Reed Pharmacy in Tucson, Ariz. "Our passion is helping people with unique needs."

But for every positive story about compounding, there seems to be another casting it in a negative light. In one egregious example of what compounders will do to increase profits, some pharmacies have even taken it upon themselves to change doctors' commercial prescriptions (often for more expensive brand-name drugs) to compounded mixtures (which can be produced less expensively) — frequently on the sly and sometimes to dangerous effect.

In 1996, Margaret Davis's lifelong lung problems — controlled by breathing two commercial medications through a nebulizer — mysteriously veered out of control. Turned out that a company, advertising the convenience of having a portable breathing machine delivered along with her meds, had faxed her doctors a form to initiate payment for the machine. They signed, unaware that hidden in the fine print was a blanket authorization for compounding. The pharmacy began substituting a compounded version of her primary medication for the real thing, adding a third that was never prescribed and mixing them all together in a way that made the drugs impossible to use correctly. Once the problem was discovered and Davis began breathing in her prescribed formula, her disease came back under control.

Who's in charge?
All compounding pharmacies are licensed and regulated by state boards of pharmacy, which have little money for enforcement. "Rigorous oversight is really a myth in most states," says Larry Sasich, MPH, PharmD, chairman of the department of pharmacy practice at the Lake Erie College of Medicine. "Inspections are few and far between."

Though the FDA regulates the safety and effectiveness of manufactured prescription drugs, it allowed the traditional compounding of individual prescription drugs — permitting compounders to make up enough products in advance to fill prescription drugs they routinely receive. But the FDA is stepping in now that compounding seems to have morphed into disguised manufacturing.
Last summer, for instance, it sent a stern warning letter to the Medi-Stat pharmacy in Mobile, Ala. On its Web site, Medi-Stat promoted its own line of pain-relieving creams that contained combinations of ingredients not proven to be safe or to work. According to the letter, it produced large volumes of the creams and employed sales reps to visit physicians' offices with promotional materials, samples, and preprinted prescription pads for the products — in short, acting like an FDA-regulated pharmaceutical company. The only difference: None of Medi-Stat's formulations are FDA approved or produced under the safe manufacturing guidelines that drug companies must follow.

As the FDA tries to take more control, compounders are stepping up self-regulation and suing to stay regulated by the states. The whole issue isn't likely to be sorted out for years. Until it is, it's essential that you make every effort to protect yourself when buying a compounded drug. In a lesson that cost Margrit Long and others their lives, it's clearly an area where medicine has the opportunity to do great harm as well as great good.

The hormone wars heat up
Bioidenticals have become the most visible targets of the FDA's recent actions on compounding . Last year, it sent warning letters to seven pharmacies charging their Web sites made unsubstantiated claims about bioidenticals. It warned pharmacies they shouldn't be compounding any prescriptions containing estriol, a weak estrogen that's promoted as safer than other hormones but isn't a component of any FDA-approved product.

Compounders and their customers are fighting back. Last fall, in an orchestrated campaign, over 25,000 patients, pharmacists, and physicians called their legislators to ask them to preserve their right to compounded medications, particularly bioidenticals, and to pass legislation to reverse the FDA's position on estriol. "If something has worked all these years, why stop it?" asks Carol Pride, 62, of Augusta, Ga., whose compounded hormonal formula was switched to the stronger estradiol after the FDA crackdown on estriol. "This is government interference."

Compounding proponents accuse the FDA of caving in to complaints by Wyeth Pharmaceuticals, the makers of Prempro, the estrogen-progestin combo deemed risky in the Women's Health Initiative study. But many independent groups, including the National Women's Health Network, supported Wyeth's request for greater regulation. For now, legislation demanding that the FDA reverse its estriol position is pending.

A guide to compounded drugs
Ask your physician to recommend a compounder, and ask the pharmacist whether she regularly compounds the drug you need. If the answer is no, look for another who does.

Confirm that a compounder is licensed and in good standing before ordering. If it's an out-of-state pharmacy, check the Web sites of the state board of pharmacy in your state and theirs, advises Carmen Catizone, DPharm, executive director of the National Association of Boards of Pharmacy. Web sites and e-mail addresses for all state boards are available at nabp.net.

Check whether an Internet pharmacy is recommended at nabp.net. Just say no if it's one of the "not recommended sites" known to be out of compliance with federal and state laws and patient safety standards.

Find out if the pharmacy is accredited by the Pharmacy Compounding Accreditation Board, which compounders established to certify pharmacies (pcab.org has a map). It's neither an absolute necessity nor a guarantee of quality, but it's one indicator that the company takes compounding seriously and practices quality control.

Research the drugs
Ask whether the same drug is available without compounding. Some pharmacists increase profits by compounding a prescription when a very similar manufactured product is available.

Check with your doctor if your drug label says it was compounded and you didn't expect it to be. All compounded medication must be labeled as such.

Think twice if prescribed a compounded version of a drug no longer on the market. Ask why and heed any safety concerns.

Think three times before getting a compounded drug in timed-release form or designed to be inhaled or injected. In general, bacteria and other impurities are most dangerous when injected or inhaled. Timed-release capsules are tricky to produce so that the drug is delivered at an even pace.

Minimize side effects
Look up your drugs. Compounded medications may come without warning labels or information about side effects, but that doesn't make them risk free. Talk with your doctor about precautions before having your prescription filled. Ask the pharmacist to show you the patient labeling for a commercial product with the same active ingredient, or look up standard warnings yourself by checking the active ingredient on Web sites such as rxlist.com.

Notify your doctor and pharmacist if your condition worsens while using compounded meds. Make sure the product isn't the problem before refilling or upping your dose.

Use, store, and discard medication correctly (ask your doctor or pharmacist). A drug compounded into a liquid form, for example, may have a very short shelf life and require refrigeration.

Copyright© 2012 Rodale Inc.All rights reserved. No reproduction, transmission or display is permitted without the written permissions of Rodale Inc.

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