Generic Drug Safety

Courtesy of Self

Bad Bargain

All of us want cheaper medicine—but not if it costs us our health. Troubling reactions and a series of recalls are making some doctors wonder, Are generic drugs as safe as the FDA says they are? Self investigates.

Just when Beth Hubbard should have been feeling great, her health fell apart. A 34-year-old housewares designer in the St. Louis area, Hubbard had recently gotten married. She liked the creativity of her career. And she’d conquered her mild depression and fatigue with a combination of exercise, rest and medicine, including the antidepressant Wellbutrin XL. But in the fall of 2006, shortly after she refilled her prescription—her pharmacy giving her this time Budeprion XL, a generic version of the drug—her good health gave way.

Within a month, she had gained 15 pounds, couldn’t sleep well, developed gastrointestinal problems and felt such extreme fatigue and lack of motivation that she thought about quitting her job. She cried and called in sick for days at a time. "I chalked it up to exhaustion after the whirlwind of the wedding and honeymoon," Hubbard says.

Yet she wasn’t getting better. Her doctor referred her to four specialists, but none, she complains, "were really listening to me—they were just anxious to give me another drug." They diagnosed her alternately with severe allergies, a heart murmur, a slow thyroid, irritable bowel syndrome, gluten intolerance, mononucleosis and chronic pain. She cycled on and off different drugs: Ambien to help her sleep at night; Provigil to keep her awake during the day; Allegra, Zyrtec and Nasacort for allergies; Lexapro, Zoloft and Xanax for anxiety and depression; Zelnorm for bowel problems. And she continued on the Budeprion XL the entire time. "I was fighting for almost a year with the insurance company over all the tests and therapy I needed," Hubbard adds.

After eight months of struggling with her mystery ailments, she was out to dinner with a friend and mentioned that she needed to refill her prescription. Her friend said she’d recently gone off Wellbutrin and had some leftover pills Hubbard could use.

Within a week, Hubbard’s troubling symptoms vanished. Her energy came roaring back. And that is when she finally connected the dots: Her problems had begun mere days after she first took the generic. Because generics had always worked well for other conditions, she says, "I never even gave it a second thought or mentioned the pharmacy’s switch to my doctor." Until now.

She called her doctor to complain about the generic and request a new prescription for the brand name only. The nurse’s response floored her. "Yes" the nurse said matter-of-factly. "We hear that all the time."

Why Your M.D. is Worried

If you took a prescription pill recently, odds are it was generic: Nowadays, generics constitute almost 70 percent of all the prescriptions dispensed nationwide, racking up $58 billion in sales in 2007. Anxious to cut costs, health insurers are stampeding to switch patients to drugs that are cheaper to make, test and ultimately buy because their manufacturers can piggyback on the research and marketing already done by brand-name-drug companies. Pharmacists in most states are also free to give patients whichever version of a drug is cheapest for them to supply, without telling the prescribing doctor; in some states, pharmacies are required to make this switch. And few of us complain when it happens: Women who wouldn’t dream of substituting Diet Pepsi for Diet Coke, simply because of the taste, eagerly swap vital medications, because the change can cut co-pays in half.

Many lawmakers and health-policy experts say the trend has little downside. "Generic drugs have the same active ingredient that brand-name drugs do and are made in FDA-approved plants, just as brand-name drugs are," says Aaron S. Kesselheim, M.D., an instructor in medicine at Harvard Medical School in Boston.

In an analysis recently published in "The Journal of the American Medical Association", Dr. Kesselheim reviewed data from 47 clinical studies and found no evidence that patients on brand-name cardiovascular drugs had clinical outcomes superior to those on generics. Given these results, and the lengths that some brand-name-drug companies have gone to protect their patents and profits, it’s easy to believe that any supposed problems with generics are "a story cooked up by Big Pharma"—the conclusion reached by consumer watchdog Peter Lurie, M.D., deputy director of the health-research group at Public Citizen in Washington, D.C.

But a yearlong investigation by Self—including more than 50 interviews and records leaked from one of the world’s largest generic-drug companies, Ranbaxy Laboratories—raises questions about whether some new generics are as safe or effective as the brand names. Although Dr. Kesselheim’s review looked at all of the available data, many of those studies were completed before the recent flood of generics hit the market and many generic-drug factories moved overseas. In FDA applications for new generic drugs, nearly 90 percent of the factories providing active ingredients are located overseas, where the agency’s inspection rate dropped 57 percent between 2001 and 2008.

"The average citizen would want to know that someone is checking that manufacturers are making the drugs they got approval to make," says William K. Hubbard of Chapel Hill, North Carolina, associate commissioner for policy and planning for the FDA from 1991 to 2005 (and no relation to Beth). "That’s not happening, and the risk to consumers is potentially huge. I take generic drugs when they’re prescribed for me, but my confidence in them is lower than it was a year ago—and going down."

Generics, which came into widespread use after Congress streamlined testing requirements in 1984, are supposed to be tightly regulated. In the late 1980s, after companies were caught paying off inspectors in order to get generic drugs approved, the FDA overhauled its rules. The agency vowed to inspect each factory before giving the green light to any application. And it newly required any generic-drug maker seeking approval to make one test lot of the proposed drug and then to produce three larger lots to show its manufacturing capabilities. "I have told the industry they are in charge of the health of the American public," says Gary Buehler, director of the FDA’s Office of Generic Drugs, adding, "We have come a long way in how we do inspections."

But Self found that the FDA’s reforms have largely fallen by the wayside. Few applications trigger inspections, according to sources knowledgeable about the process, and instead of the three required lots, companies are making one or none. Manufacturing problems have come to light, with six generic companies recalling 20 products in 2008. KV Pharmaceutical Company, a maker of heart and pain medicine, recalled everything it made. "The FDA is satisfied that generics are OK," says Nada Stotland, M.D., a psychiatrist in Chicago and the president of the American Psychiatric Association. "My question is, Are we satisfied?"

Next: The Difference Between Generic and Brand Name Drugs