Sunday, January 02, 2005
Copyright © Las Vegas Review-Journal

CONCERNED PATIENTS: Drug news has doctors in dilemma

Effective treatments for arthritis pain linked to increased cardiovascular risk

A bottle of Vioxx is photographed at a pharmacy in New York City after its manufacturer, Merck & Co., announced a worldwide voluntary withdrawal of the arthritis medication. Photo by THE ASSOCIATED PRESS

Their patients' concerns come by way of phone calls. Many, many phone calls. The concerns also come during hastily scheduled, and, more and more frequently, unscheduled visits.

Those concerns, sometimes accompanied by tears, generally boil down to this question: "What should I do now that I've found out the medicine I take for pain may give me a heart attack?"

Las Vegas Valley physicians who care for patients who suffer from painful, disabling arthritis, say the question is becoming increasingly difficult to answer.

The three drugs doctors were prescribing most for arthritic pain are now under intense scrutiny. Vioxx, Celebrex and Bextra -- which held great promise to relieve suffering from arthritis without causing the digestive discomfort and internal bleeding associated with older medications -- have all been linked to an increased risk of cardiovascular problems.

"I certainly can't blame the patients for being concerned," said Dr. Michael Colletti, a rheumatologist and president of the Clark County Medical Society.

Colletti said he has been inundated by calls and visits from worried patients. "This is a very confusing time for patients and physicians, without any easy answers."

In September, Vioxx, an arthritis and acute pain medication taken by an estimated 80 million people worldwide, was taken off the market when studies showed it increased the risk for heart attacks and strokes. FDA researcher Dr. David Graham testified before Congress the drug caused more than 100,000 people to have heart attacks and that more than 27,000 people died as a result.

In December, the FDA urged doctors to limit prescriptions for Celebrex and Bextra because of similar concerns.

"I'm doing a lot of research to find substitutes for these drugs for my patients," said internist Dr. William Schofield.

Physicians, according to Schofield, have often been as confused as the public regarding the drug safety issue.

"The day before Vioxx was taken off the market, Vioxx drug salesmen came to my office saying it was the best pain medication for arthritis there was," Schofield said. "I don't think physicians should find out about problems with medicines on the 5 o'clock news."

Confusion regarding painkillers became even more pronounced less than a week after the warning about Celebrex and Bextra.

The FDA issued another warning, this time to users of naproxen, sold over-the-counter under the brand name Aleve. Studies showed it, too, led to an increased number of heart attacks and strokes.

Dr. Julio Garcia, a Las Vegas plastic surgeon who often suggests Aleve to patients for pain, said the data physicians receive about medications "is less than optimal."

"In this age of the Internet, we should have an easy place to go to find information on medications of all sorts," he said. "Most physicians get their information from drug representatives that come to the office. We need to see all the studies on a medication.

"The negative studies are not as well publicized by the drug companies as the positive ones," he added.

Susan Mazor, who suffered a near fatal heart attack in 2001 after two years of taking Vioxx for arthritic pain, said she "just always assumed that the government wouldn't allow drugs to be sold if they were so dangerous."

"It makes you think that maybe money is more important than people," said Mazor, who is pursuing litigation.

If that perception becomes generally accepted, the country's health care system is in serious trouble, according to Colletti. "We need to see the FDA as our protector and our employee, not as an organization that is getting paid by drug companies to get drugs on the market," he said.

Increasingly, the FDA is receiving criticism that it shortchanges public safety. No one has been more outspoken than the FDA's Graham, a researcher who told Congress that "the FDA, as currently configured, is incapable of protecting America against another Vioxx."

The 1992 congressional passage of the Prescription Drug User Fee Act, which has pharmaceutical companies paying for FDA review of drugs, makes it impossible for the agency to work in the public interest, according to Dr. Sidney Wolfe, head of the Health Research Group of Public Citizen, an advocacy organization founded by consumer activist Ralph Nader.

"This funding of the review process has created a relationship where the FDA says, `They are paying our bills so we have to be nice to these people,' " Wolfe said in a telephone interview this week from his Washington, D.C., office. He favors a return to public appropriations for review of drugs.

Susan Cruzan, an FDA spokeswoman, disputes claims of favoritism toward pharmaceutical manufacturers and says decisions are based in science. "We've maintained a good firewall between payment of user fees and the review of drugs," she said.

Colletti, who believes the FDA must do a better job of removing any public fear of collusion between the agency and pharmaceutical companies, stressed there will never be a drug put on the market that is without risk.

The FDA's position on the marketing of drugs, according to spokeswoman Cruzan, is outlined in an agency publication.

The FDA notes it can't make risk go away, and doesn't represent that it can. Labeling should make risks clear.

If 500 people are used in a study there is much more uncertainty about a drug than if 150,000 people participate. But when more people are studied, the agency says, the cost can become prohibitive, stalling other drugs in the pipeline.

Once a drug is on the market, a reporting system is in place to track it, the agency says. Physicians, pharmacists and patients can report serious adverse reactions to the agency or the manufacturer, which will then send it to the agency. The FDA monitors the reports and if a new finding exists, it will be added to the label of the medicine.

If a safety issue alters the risk-benefit ratio so the risks of the drug, including the newly found risks, outweigh the benefits, the FDA will have the manufacturer take the drug off the market, the agency says.

Colletti believes that the new class of drugs approved by the FDA for arthritic pain, including Vioxx and Celebrex , have been excellent drugs.

"Vioxx really helped some of my patients," he said.

Most of the problems with the arthritic pain drugs, he suggests, have come about because the medications are not taken in the correct dosages over a proper period of time.

Colletti said people should remember the drugs they replaced, such as ibuprofen, caused severe gastrointestinal problems in some patients, resulting in more than 16,000 deaths per year.

Neither Colletti nor Schofield believe many doctors will be prescribing Celebrex or Bextra to patients, even if they believe it will help their arthritis.

Schofield said that for now, he is advising longtime users of Celebrex to keep taking the drug but to accompany it with a baby aspirin. This, he said, should take care of the coagulation defect that may be present in Celebrex. He's not putting any new patients on Celebrex.

Schofield also is recommending the use of older anti-inflammatories such as ibuprofen, naproxin, feldene and aspirin. He's recommending those treatments in conjunction with drugs that protect the stomach lining, such as Nexium and Prilosec.

"Given the threat of litigation, you really have no choice but to pull back," Schofield said. "For some people you're going to hate to take them off the medication because it's working so well. But you have to in today's legal climate. I'm just going to have to try and find other medications for patients."