Vioxx (Rofecoxib)
Generic name: Rofecoxib

Vioxx Complications
and Safety Risks

Studies Find Higher Rates of Heart Risk With Vioxx

Vioxx, which is no longer on the market, may have posed heart risks that a similar drug, Celebrex, and other painkillers do not, according to two papers published yesterday by The Journal of the American Medical Association.

In one paper, three researchers at Harvard examined 114 clinical trials of Vioxx and other drugs and found that Vioxx was linked to substantially higher rates of increased blood pressure than was Celebrex, a similar painkiller, which is still sold.

In the other paper, two Australian researchers found that Vioxx appeared more dangerous than Celebrex or several older painkillers in observational studies, which examine the safety and effectiveness of drugs in real-world settings after they are approved.

These conclusions were hardly surprising. Merck, which makes Vioxx, stopped selling the drug in 2004 after a clinical trial showed that it sharply increased the risk of heart attacks and strokes.

But the papers provide new grist for the debate over whether all painkillers raise heart risks, or whether Vioxx is uniquely dangerous.

The question has scientific and legal implications. About 30,000 people have sued Merck, saying they or members of their families had heart attacks or strokes after taking Vioxx. Merck has argued that all painkillers appear to carry some heart risks, while many scientists say Vioxx appears riskier than other medicines.

Merck disputed the findings published yesterday, saying in a statement that it did not believe Vioxx was more dangerous than other painkillers. The company also noted that Vioxx’s label had always warned of its potential to cause high blood pressure. Vioxx and Celebrex are part of a class of drugs developed in the 1990’s called cox-2 inhibitors. They are designed to reduce pain and inflammation without causing stomach or gastrointestinal bleeding.

In the Harvard study, the three researchers examined clinical trials conducted in the last decade on the cox-2 drugs. Their analysis showed Vioxx was associated with increases in rates of high blood pressure in 40 clinical trials covering 38,000 patients. High blood pressure, or hypertension, is closely linked to heart attacks and congestive heart failure. Vioxx was also associated with heart rhythm disturbances, kidney problems and edema, or swelling.

“This study merely confirms what has been known about Vioxx for several years,” said Eric Weinberg, a lawyer who represents people suing Merck over Vioxx. “It’s no surprise.”

But the study’s authors also found that Celebrex, which is made by Pfizer and remains on the market, was actually associated with somewhat reduced rates of kidney problems and hypertension. The researchers examined 37 Celebrex trials, covering 45,000 patients. The other drugs, including Bextra, a Pfizer painkiller that has been withdrawn, had no association, positive or negative, with kidney problems and hypertension.

The analysis cannot confirm that Vioxx is uniquely dangerous or Celebrex uniquely safe. The drugs could cause heart problems in ways beyond raising blood pressure, such as by increasing the risk of blood clots. But it provides a signal that Vioxx may be more dangerous than Celebrex and other cox-2 drugs, said Eric Ding, one of the paper’s authors.

“We cannot necessarily say all cox-2 drugs have similar adverse risk profiles,” Mr. Ding said, “which has implications for the ethical development and testing of future drugs in this class.”

The paper written by the two researchers at the University of New South Wales in Australia examined the results of observational studies that covered the cox-2 drugs and older painkillers. The researchers found that Vioxx had more heart risks than Celebrex and that naproxen, an older painkiller, appeared to be even safer.

Warning Over Common Drugs

Commonly prescribed drugs for arthritis, depression and epilepsy have been linked to a range of potentially serious side effects including heart attacks, convulsions and birth defects.

The October bulletin of the federal government's Adverse Drug Reactions Advisory Committee (ADRAC) contains warnings about the arthritis drugs Celebrex and Vioxx, the anti-depressant mirtazapine (marketed as Remeron, Avanza and Mirtazon) and anti-epilepsy drugs including Epilim and Valpro.

ADRAC warns of a possible increased risk of heart disease and cerebrovascular complications linked to Celebrex and Vioxx.

Painkillers Blamed For Infertility

Women who want to become pregnant have been warned not to take the popular pain drugs Celebrex and Vioxx because of emerging evidence that they can cause temporary infertility.

The drugs, known as COX-2 inhibitors, might also prevent implantation of embryos or trigger early miscarriage, said Professor Norman, head of reproductive medicine at the University of Adelaide.

"Normal women of childbearing age attempting to have a baby should avoid taking these drugs or reduce their dose while seeking pregnancy," he wrote in the journal Fertility and Sterility, published by the American Society for Reproductive Medicine.