Feb. 11 (Bloomberg) -- Ginny Miller blames her son’s string of epileptic seizures on a generic medicine that she says she expected to work as well as the original brand-name treatment.

Sam, 17, went seven weeks without an episode while taking Zonegran, made by Tokyo-based Eisai Co. After pharmacists switched him to generic copies made by four different companies, he suffered multiple seizures daily and was hospitalized three times before doctors identified differences between the medications as the cause, said Miller, of Dayville, Connecticut. She said her son’s doctor was never notified about the switches and she didn’t always know what company supplied the pills.

Armed with more than 1,000 similar reports, the Epilepsy Foundation of America and other patient-advocacy groups are pressing lawmakers in at least 33 states to stop pharmacies from substituting generic drugs for the originals before patients and their doctors are alerted to the changes.

“We can lose our lives over this; we can lose our jobs,” said Ginny Miller, 45, who also has epilepsy, in a telephone interview. “If I’m out there driving, with a generic medicine that I’m sensitive to, I might kill you. A lot of patients don’t have a choice but to use the generic. Their hands are tied.”

Products such as Zonegran and Johnson & Johnson’s Topamax, also for epilepsy, may gain sales if the bans pass. Teva Pharmaceutical Industries Ltd., Mylan Inc. and other generic- drug makers might lose $29 billion over 10 years, the Pharmaceutical Care Management Association, based in Washington, said in a report in October.

Generic Sales

U.S. retail sales of generic medicine totaled $33 billion last year, IMS Health Inc., a Norwalk, Connecticut-based research company, said in a December report.

Generic drugs, copies of medicines that have lost patent protection, can cost 70 percent less than the originals. States, insurers and employers often insist that pharmacists fill patients’ prescriptions with a generic to save money.

Last year, 71 percent of prescriptions were filled by copies, a portion that has climbed since a 1984 U.S. law established the current system for allowing generic drugs on the market, IMS said.

While routine switching of drugs may make sense for many patients, a growing number with epilepsy, depression, heart disease and transplanted organs have suffered side effects after getting generic substitutes, say spokesmen from the Epilepsy Foundation in Landover, Maryland; the American Academy of Neurology in St. Paul, Minnesota; the American Heart Association in Dallas; and the National Kidney Foundation in New York.

Surprising Effects

The chance of adverse effects may surprise most patients who use generic drugs, said Barbara Murphy, chief of nephrology at Mount Sinai School of Medicine in New York. Individual patients, doctors and the government have to be aware of the possibility, she said.

“Doctors and patients do need to be involved in the decision to change to a generic,” said Murphy, who is also president of the American Society of Transplantation, in a telephone interview. “It shouldn’t be made by whatever pharmacy the patient happens to go to. And generics should have to go through more-rigorous evaluations.”

Besides seizures, differences between original drugs and their generic forms may be linked to side effects and relapses in people with depression, rejection of transplanted organs and irregular heartbeat, according to the patient groups.

No definitive studies have compared brand-name drugs against generics using double-blind tests, which would require epileptic volunteers to take medicine that might cause a seizure relapse, said Jacqueline French, director of the Epilepsy Clinical Trials Consortium at New York University, in a telephone interview.

Chemical Differences

What is known is that generic copies of medicines can have a chemical makeup different from that of the originals, under rules issued by the U.S. Food and Drug Administration, said Eric Hargis, president of the Epilepsy Foundation.

While the FDA requires that generic versions contain the same active ingredient as the original, the amount that makes it into a patient’s blood can vary. To get products approved, makers of generics must show the medicines deliver to the bloodstream 80 to 125 percent of the amount of active ingredient deposited by the original drug. Colorings, binders and fillers also may differ from those of the original product.

While generics can vary that much, on average they don’t, said Kathleen Jaeger, chief executive officer of the Generic Pharmaceutical Association in Arlington, Virginia. A 1997 study in the Journal of the American Medical Association found the average difference in blood levels between generics and originals was less than 4 percent, she said in a telephone interview. That’s the latest large-scale, published study to measure the difference, she said.

‘No Better or Worse’

“By federal law, generics have to be the same -- they can’t be any better or worse,” Jaeger said.

Still, “there are a lot of smoking guns here,” Hargis said. The Epilepsy Foundation has received more than 1,000 reports from people whose seizures worsened or who had side effects after their pharmacy switched between different generic copies of the same medicine, he said.

Cases of alleged side effects from switches to generics may stem from coincidence or from a natural progression of illness, said Jaeger of the industry association. The group opposes state legislation that limits drug changes, as do the Washington-based American Pharmacists Association and Minnetonka, Minnesota-based UnitedHealth Group Inc., the nation’s largest health insurer.

Teva’s director of state government affairs, Jerry Moore, who has been campaigning against curbs on switching patients to generic drugs, said people should feel confident in using generics because the products have been ruled safe by the FDA.

Diet, Environment

Individual cases of side effects may be based on changes in diet, lifestyle, or environment, Moore said. Also, under current rules, doctors can ask pharmacists to give their patients the original medicine, he said in a telephone interview.

There isn’t enough data to support placing a warning on drugs’ prescribing information, said FDA spokeswoman Sandy Walsh. As a result of the patient complaints, the agency is designing research to be carried out by the National Institutes of Health to determine whether blood-level variations between drugs are tied to an increase in seizures.

The first study results may be available in a year, said Michael Privitera, director of the epilepsy center at the University of Cincinnati, in a telephone interview. The center is helping design the research.

State Measures

North Carolina, Tennessee, Utah and Hawaii passed measures that stop pharmacies from automatically switching customers on prescription medicines to generics, according to the Generic Pharmaceutical Association. Now, druggists in those states must get patient or doctor consent, or sometimes both, for switches involving some classes of medicine.

Patient advocates say cases of side effects tied to variances between generic medicines and originals will increase. About $120 billion of medicines, including half of the top 20 original brand-name drugs, are due to lose patent protection by 2013, according to IMS.

MassHealth, the Massachusetts-run health insurer, switched Lynn Dann, a Boston lawyer, to the generic version of GlaxoSmithKline Plc’s anti-seizure drug Lamictal because of the cost. Within 24 hours, Dann’s face began to twitch and a day later a convulsion knocked her out of her chair, she said.

“I know this happened because of the drug,” Dann said in a telephone interview. “I was happy. It was around the time of my cousin’s wedding. Then I couldn’t get out of bed. I couldn’t release the tension and was begging for the other pill.”

Anecdotal Evidence

Generic-drug makers and health insurers say anecdotal evidence falls short of definitive proof that differences between generic medicines and the originals cause side effects, said the generic industry’s Jaeger.

Restrictions on prescription switching would unnecessarily raise costs for patients and governments, Jaeger said.

“It is foolish in this economic time for misinformation to allow certain drugs to be carved out” from rules allowing pharmacists to substitute cheaper alternatives to drugs, Jaeger said.

An analysis of patient records published in July and funded by Abbott Laboratories, maker of the anti-seizure medicine Depakote, found that epileptics who switched to a generic had an 81 percent higher risk of hospitalization within six months.

The study, in the journal Epilepsia, wasn’t controlled to rule out unrelated factors and thus didn’t persuade the FDA to consider warnings, said the University of Cincinnati’s Privitera.

Journal Report

Another analysis, published on Dec. 3 in the Journal of the American Medical Association, found no difference in effects of original and generic versions of heart drugs.

That analysis was supported by the Attorney General Prescriber and Consumer Education Grant Program, a fund that resulted from a settlement between New York-based Pfizer Inc., the world’s largest drugmaker, and the attorneys general of the 50 states and the District of Columbia over the marketing of Neurontin, an epilepsy treatment. The fund is administered by the Oregon Department of Justice, in Salem.

Miller, who volunteers for the Epilepsy Foundation, said she won’t give her son generic drugs again. He now takes Topamax.

She hopes her son will avoid further convulsions, Miller said.

“It is so scary when you’ve never had something like that happen before,” she said.

To contact the reporter on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net

Last Updated: February 11, 2009 00:00 EST