The Food and Drug Administration on Thursday announced that dozens of popular prescription painkillers must now carry the government’s strongest warning about the risks of serious heart attacks and strokes.

Makers of over-the-counter nonsteroidal anti-inflammatory drugs, or NSAIDs - a category of drugs that includes Aleve, Advil and Motrin - have also been ordered to add strong warnings to the drugs’ packaging to take only low doses for a few days at a time to avoid the risks of high-dose, long-term use.

One drug, Pfizer’s blockbuster painkiller Bextra, was ordered off the market - the FDA said the risk it posed of serious side effects, including a potentially fatal skin reaction, outweighed the benefits.

The new FDA warnings don’t apply to aspirin, which the agency says has “clearly been shown” to reduce the risk of serious cardiovascular problems in certain patients.

Now, doctors must find alternative treatment for their patients. Michele Norris talks with Dr. Joshua Prager of the California Pain Medicine Center at UCLA.

Below is a summary of the new painkiller warnings from the FDA:

Bextra: Data suggesting short-term heart risks associated with the use of Bextra, lack of data on the safety of long-term use, and reports of serious, potentially life-threatening skin infections prompted the FDA to ask the company to pull this drug from the market.

Celebrex: The FDA says doctors should prescribe the lowest effective dose for the shortest amount of time possible. The FDA has asked Pfizer, the drug’s maker, to revise Celebrex’s packaging to include a “black box” warning - the strongest possible - on the heart and gastrointestinal risks associated with NSAIDs in general and Celebrex in particular. The FDA also wants Pfizer to commit to a long-term study comparing the safety of Celebrex to that of naproxen and other drugs. Patients taking Celebrex are urged to discuss the FDA’s new advisory with their doctors.

Prescription and Over-the-Counter Non-Selective NSAIDs: Long-term, controlled clinical trials have not been conducted for most NSAIDs on the market, a large category of drugs that includes such well-known brand names as Aleve, Motrin and Advil, as well as products containing diclofenac. All makers of these drugs will be asked to review and analyze existing data from controlled clinical trials and conduct long-term trials.

Prescription NSAIDs will now carry a black-box warning on the potentially serious heart and gastrointestinal risks they pose, as well as a contraindication for use in patients who’ve recently undergone coronary artery bypass surgery. Patients taking prescription non-selective NSAIDs are urged to talk to their doctors about the new information regarding these drugs.

In the health advisory it issued Thursday, the FDA said using over-the-counter NSAIDS for short periods of time and at low doses likely doesn’t increase cardiovascular risks. Still, it has ordered revisions to labels on these over-the-counter NSAIDs to include stronger reminders about limiting the dose and duration of treatment, and a warning that people taking the drugs are at an increased risk for heart attacks, stroke, gastrointestinal bleeding and serious skin reactions.

Covered Under the New Warnings

Among the drugs covered under the FDA’s new warnings:

 
• Naproxen: Aleve, Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole)  
• Ibuprofen: Motrin, Motrin IB, Motrin Migraine Pain, Advil, Advil Migraine Liqui-gels, Ibu-Tab 200, Medipren, Cap-Profen, Tab-Profen, Profen, Ibuprohm, Children’s Elixsure, Vicoprofen (combination with hydrocodone), Combunox (combination with oxycodone)  
• Diclofenac: Cataflam, Voltaren, Arthrotec (combination with misoprostol)

How conventional pain therapies work
Over half of the people who experience chronic pain are taking prescription painkillers. Here’s a rundown of the most popular drugs for chronic pain and how they work:

NSAIDs
NSAIDs, or non-steroidal anti-inflammatory drugs, suppress the inflammatory process that results in pain. They make you feel better by reducing the amount of discomfort experienced but do not inhibit the actual disease process. In the case of arthritis, they do not help repair the damage associated with the condition, such as bone and joint impairment.

Potential side effects of NSAIDs include stomach pain, gastro-intestinal bleeding, vomiting, rapid heartbeat, fainting, and blood in the urine. In many cases NSAIDs can actually increase arthritic inflammation due to their effect on the lining of the intestine. (These drugs may increase the porosity of the intestinal wall, causing “leaky” gut syndrome, which contributes to the inflammatory process.)

Ironically, more people die from the gastro-intestinal bleeding caused by NSAIDs than die from the diseases for which they are primarily prescribed—arthritis and other degenerative disease of the joints. In the US alone, it has been estimated that 107,000 patients are hospitalized each year as a result of prescription NSAID use. Close to 16,500 die. Over-the-counter NSAIDs, including ASA (acetylsalicylic acid or Aspirin®) and other painkillers, account for a further 40,000 deaths each year.i

Since NSAIDs inhibit the blood’s ability to clot properly, they may interact with blood thinning medications such as coumadin. Kidney disease has also been reported as a side effect.

Due to the litany of side effects associated with NSAID use, and the long list of patients for whom they are not suited (people with stomach ulcers or elevated blood pressure, for example), in the late ‘90s, drug companies brought to market a new class of anti-inflammatory drugs known as Cox-2 inhibitors.

Cox-2 INHIBITORS
Older NSAIDs reduce inflammation by blocking an enzyme known as Cox-2. In doing so, they also block another enzyme called Cox-1, which helps to protect the lining of the stomach. (The reason NSAIDs cause stomach bleeding in some individuals is due to the blocking of Cox-1.) Cox-2 inhibitors are more selective, blocking only the Cox-2 enzyme and leaving the stomach-protecting Cox-1 alone. In theory, less risk of bleeding should occur with use of Cox-2 inhibitors.

Unfortunately, the Cox-2 inhibitors have not proven to be the panacea they were first believed to be. They do little to reduce the incidence of stomach bleeding, and recent studies have confirmed that they increase the risk of heart attack and (in the case of Vioxx®), stroke.*

ACETAMINOPHEN
While acetaminophen is an effective treatment for moderate pain and fever, it is ineffective against inflammation and swelling. The side effects associated with acetaminophen are many and disturbing. They include anaemia and severe liver damage. Damage to the cells of the liver may accompany short-term use (high doses) or long-term use. Since many over-the-counter medications contain acetaminophen, including cough and cold formulas, backache medications and headache remedies, it is easy to exceed the recommended maximum dose. Liver damage is increased when acetaminophen is combined with alcohol.ii

CORTISONE
Cortisone may be injected directly into the joint to relieve severe inflammation and swelling. Cortisone mimics the anti-inflammatory effects of cortisol —a hormone produced naturally in the body. A cortisone injection can provide almost immediate relief for a tender, swollen or inflamed joint. Since corticosteroids can weaken cartilage and remove minerals from the bone (osteoporosis and osteopenia), they should only be used rarely. Chronic use of corticosteroids may result in immune suppression and increase the risk of infection.