Bextra and other drugs pulled

At the end of September 2004, Merck announced a voluntary worldwide withdrawal of its COX-2 inhibitor VIOXX® (rofecoxib), an arthritis and acute pain medication. The company took the decision when the drug was linked to more than 100,000 heart attacks and strokes in the United States. Attention quickly shifted to Pfizer, who had two similar drugs valdecoxib (BEXTRA®) and celecoxib (CELEBREX®) on the market. Many had expected that these drugs would also be withdrawn. However, in a surprising stance Pfizer stood by its COX-2 inhibitor drugs and even announced that it was looking into whether it’s best-known and biggest selling COX-2 inhibitor CELEBREX® might actually help prevent heart attacks. Pfizer may now be regretting that decision as the FDA has requested that valdecoxib (BEXTRA®) is withdrawn from the market stating that the overall risk versus benefit profile for the drug is unfavorable.

Double whammy

In Pfizer's case, the withdrawal of BEXTRA® came along with the news the FDA will also require the company to add a black-box warning to the popular and bigger-selling drug CELEBREX®. The labeling must now include a black-box warning, highlighting the potential for increased risk of cardiovascular events and the potential life-threatening gastrointestinal bleeding associated with the use of COX-2 inhibitors.

Celebrate Celebrex

Many observers were surprised that the FDA did not insist that CELEBREX® was also withdrawn from the market. The agency commented that it had singled out BEXTRA® for suspension as it affords no added advantage as a painkiller and in addition can also cause a potentially life-threatening skin condition called Stevens-Johnson syndrome, an allergic reaction that usually begins as a blistering of the mouth and lips and can spread to the rest of the body. Pfizer do have some cause for celebration in that CELEBREX® is now the only selective COX-2 inhibitor on the market. In 2004, 23.9 million prescriptions were written for CELEBREX®, and Pfizer hope that this will increase in 2005. The news isn’t so good for Merck who had hoped to get VIOXX® back on the market. If the FDA had asked Pfizer to temporarily suspend BEXTRA® that might have indicated a positive thing for VIOXX® but the all-out withdrawal indicates a bleak future for VIOXX®. The black-box warning required by the FDA will make it increasingly difficult for Pfizer to continue with the direct-to-consumer advertising of CELEBREX® which has already come under criticism for not being careful enough about presenting potential side effects.

Patients feel the pain

Many arthritis sufferers who had been taking VIOXX® switched to the other COX-2 inhibitors that were on the market. For those patients that made the change to BEXTRA® they are now facing the challenge of finding another drug to treat their arthritis associated pain. Some may switch to Pfizer’s other COX-2 inhibitor CELEBREX® and others may switch to the older non-selective non-steroidal anti-inflammatory drugs (NSAID) such as ibruprofen or naproxen which have the added advantage of being available over-the-counter. However, the FDA is also requiring that that all manufacturers of NSAIDs revise their labeling to provide more specific information about the potential cardiovascular and gastrointestinal risks of their individual products. This may cause some concern to patients and some may feel they want to abandon this class of drugs altogether in favor of something else such as acetaminophen or aspirin - the only pain relievers available without the new FDA required warnings.

Pass the aspirin

According to some estimates, a trillion aspirin tablets have been taken in its long history. Aspirin is effective, relatively safe and is extremely cheap. So what's not to like about aspirin? Well, for some compliance may be a real issue as patients have become used to their one-a-day options. To get the same anti-inflammatory effect as one 200-milligram CELEBREX®, it may be necessary to take 12 or 14 aspirin. For simple pain relief, the dose would be approximately four to six tablets a day. Also there is a psychological aspect to pain relief; many patients just don't think aspirin works as well as newer more expensive, anti-inflammatory drugs. With the low cost of aspirin, it’s also unlikely that the pharmaceutical industry will spend money on marketing the benefits of aspirin.

Widely recognized as easier on the stomach than aspirin, acetaminophen is another alternative that is safe to use and readily available, but overdose is a problem as the drug is highly toxic to the liver.

Off to court

When a pharmaceutical company takes the dramatic step of taking a $1 billion medicine off the market, one can be sure that lawyers will be quick to offer their services to patients and investors eager to sue. However, it may seem bizarre but Pfizer, a drug company who were forced to withdraw their drug may not experience the same flood of lawsuits as Merck, a company who voluntarily withdrew their drug. The difference is that in the case of BEXTRA®, the FDA cited an increased risk of rare but serious skin reactions as having tipped the balance against Pfizer's painkiller. Regulators concluded the risk of heart attack and stroke was comparable to other medicines. Luckily for Pfizer, they have included a warning about skin reactions on BEXTRA® labels for over a year. This is expected to help limit potential legal liability since the skin problems occur far less frequently than the cardio-vascular events. But they will certainly not escape the courthouse. A series of securities lawsuits have been filed accusing Pfizer executives of damaging investors by making false and misleading statements about the safety of CELEBREX® and BEXTRA®. Several consumer lawsuits and product liability cases have also been filed alleging that the company misled patients who bought BEXTRA® and caused serious health injuries to those who took the drug.

Kudos to the FDA

The FDA must be given credit for their tough stance on protecting the public health. Observers feel that the decision to withdraw BEXTRA® may represent a shift in the agency’s management of a drug’s risk-benefit equation with focus changing from emphasizing the benefit of a product to managing any associated risk. However, whether the agency will have the courage to continue with this tough approach when another unsafe drug inevitably comes along and when the publics’ attention is diverted elsewhere is uncertain. Let’s hope so – even if the drug is CELEBREX®.