Parker Waichman LLP Injury Alerts
ARTHRITIS DRUGS: Is the Promise of Relief Worth the Serious Health Risks They Pose?Aug 1, 2004 As the “baby boomer” generation ages, rheumatoid arthritis (RA) is rapidly becoming a serious medical problem affecting millions of men and women over 50. Anticipating a lucrative market for prescription painkillers (analgesics) and anti-inflammatory medications as well as non-prescription, over the counter (OTC) products (balms, ointments, topical analgesics, heat packs and pads, etc.), pharmaceutical manufacturers have invested hundreds of millions of dollars in the development of “treatments” for every degree of this potentially disabling medical condition.
To be sure, RA in its most serious forms produces excruciating pain, physical deformities, and significant restrictions of motion. It can prevent people from performing their jobs, daily activities, and the simplest of tasks. Even milder cases of RA are capable of causing chronic problems which send sufferers desperately searching for relief. While OTC pain relievers, topical analgesics, and heat-producing products are relatively safe, the relief they provide is limited and of short duration. For this reason, the more potent, long-lasting prescription drugs are far more attractive to those suffering from RA. Some of the drugs like Celebrex and Vioxx relieve pain and inflammation associated with RA while others like Enbrel, Remicade, Humira, and Arava claim to slow the progression of RA.
Unfortunately, all of these drugs have potentially serious, and sometimes deadly, side effects which make their use quite problematic and risky. This is yet another example of a “risk versus benefit” situation which must be carefully evaluated to determine if the severity of the potential risks is really worth the benefits claimed to be offered by the various drugs. Thus, it is imperative for people being treated for arthritis to have a full and complete understanding of the medications that are being prescribed to them.
Product inserts, warning labels, reports by consumer watchdog organizations, and any other available information should be carefully reviewed before beginning any treatment regimen that includes one or more of these drugs. Patients are encouraged to ask their doctors and pharmacists any questions they may have concerning these drugs. Careful medical monitoring is also critical while these drugs are being taken, and patients must be aware of the symptoms and warning signs associated with the various side effects involved. This Newsletter will discuss the following prescription drugs currently used to treat arthritis: Vioxx, Celebrex, Enbrel, Methotrexate, Remicade, Arava, and Humira.
Vioxx and Celebrex:
Vioxx, otherwise known as rofecoxib, is a non-steroidal anti-inflammatory drug prescribed to alleviate pain and symptoms such as swelling and soreness associated with osteoarthritis. It is also prescribed for menstrual cramps and other acute pain in adults. Like most arthritis medications, however, Vioxx may not be right for everyone. Merck, the manufacturer, provides a list of potential side effects on the patient information leaflet distributed with the drug. The serious side effects listed are stomach, kidney, and liver problems as well as intestinal bleeding. Less serious side effects include headache, dizziness, diarrhea, nausea, stomach pain, swelling (legs or feet), high blood pressure, back pain, tiredness, and urinary tract infection.
The risk of a serious or mild side effect is unavoidable with the majority of prescription drugs on the market today. The problems associated with Vioxx, however, extended beyond the original warnings provided. In fact, those warnings were eventually found to be inadequate as they did not stress the severity of certain side effects. In 2001 a study called VIGOR (Vioxx Gastrointestinal Outcomes Research Study) found that Vioxx users potentially faced an increased risk of heart attacks and strokes, two side effects that were never listed in the patient information at all.
The increase in heart attacks was combined with an increase in other blood-clot related adverse effects. Merck first received a letter from the FDA requesting the manufacturer to amend its advertising campaign and to update the warning label to include information regarding cardiovascular risks. When Merck did not take action by April of 2002, the FDA made the new warnings mandatory. Now, people with heart disease are urged to seek medical advice before taking Vioxx for osteoarthritis or any other reason.
Celebrex is another heavily advertised arthritis drug (distributed by Pharmacia) with side effects such as nausea, diarrhea, heartburn, and stomach problems such as pain, ulcers, and bleeding. Celebrex is commonly associated with Vioxx as both are classified as COX-2 inhibitors and both have similar benefits for treating osteoarthritis. Unfortunately, they also have similar risks.
After news of a potential cardiovascular risk, the American Heart Association, the National Stroke Association, and the Arthritis Foundation requested that safety studies be conducted on Vioxx and Celebrex. Merck and Pharmacia argued that their products were safe and said they did not plan to conduct any such trials. Notwithstanding the companies’ claims regarding the safety of their products, the cardiovascular risks do appear to be quite real. Choosing to leave patients under-informed may prove costly to both companies in the long run. Vioxx and Celebrex are two of the top-selling arthritis drugs and, at the time of their release, were #1 and #2 in sales for Merck and Pharmacia respectively.
Other potential side effects or dangers associated with Vioxx and Celebrex include:
• Both may cause an increased risk of bleeding ulcers.
• Misuse of Vioxx, such as increased dosage, can lead to high blood pressure and swelling.
• Both may cause temporary infertility and increased risk of miscarriage for women.
• Vioxx has been linked to a few cases of a nonbacterial type of meningitis. While no cases were fatal, the FDA required Merck to add meningitis to the list of potential side effects.
• Vioxx and blood pressure medications should not be taken at the same time as the combination increases the risk of heart attack.
The debate over label changes for Vioxx and Celebrex continues while the companies attempt to market the drugs without addressing some of the more serious issues. Commercials for Vioxx and Celebrex show people happily resuming their normal activities without arthritis pain. (The risks, however, are either recited very quickly or shown in very small print at the bottom of the advertisement). Such claims of pain relief are extremely attractive to anyone suffering from chronic arthritis. While some patients may, in fact, obtain such relief, anyone considering a treatment regimen involving either drug should certainly consult a physician beforehand.
A recent study suggests that non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen and naproxen may be more cost-effective and safer than COX-2 inhibitor pain killers such as Vioxx and Celebrex.
Arava, otherwise known as leflunomide, is a pyrimidine synthesis inhibitor used to treat rheumatoid arthritis. Possible minor side effects associated with Arava include nausea, diarrhea, headache, pain, back pain, muscle aches, runny or stuffy nose, weight loss, and hair loss. Somewhat more serious side effects include chest pain, blistering or peeling skin, skin rash, sores or blisters, fever, sore throat, feelings of numbness or tingling, pale skin, yellowing of skin or eyes, dark urine, pale stools, fatigue, muscle cramps, vomiting, or easy bruising or bleeding. Arava may also lower resistance to infections, making the body more susceptible to minor illnesses such as the common cold.
There are, however, a number of significant risks associated with Arava. The drug can be harmful to the human fetus and therefore a pregnancy test is required for women before beginning treatment. Arava may also cause birth defects of children of men taking Arava at the time of conception. It is possibly secreted through breast milk although this is not a certainty. In addition, since Arava may remain in the body for quite a long time, a woman should avoid becoming pregnant for at least 2 years after discontinuing the drug. A procedure than can remove the medicine from the body more rapidly is available but only under medical supervision.
Arava has recently been linked to:
• Harmful liver damage (in November 2003, France’s largest pharmaceutical company, Aventis SA, warned doctors that Arava could cause serious liver damage);
• Sepsis, which is a severe (and sometimes fatal) illness caused by overwhelming infection of the bloodstream by toxin-producing bacteria; and
• Stevens-Johnson syndrome, a potentially life-threatening skin condition characterized by lesions on the skin, fever, headache, chills, and all around malaise.
If you are taking Arava and are experiencing any of the aforementioned side effects, speak to your physician immediately about discontinuing treatment. Merely stopping treatment on your own may be quite problematic since, as discussed above, Arava stays in for an extended period of time and can only be removed on an accelerated basis under medical supervision.
Methotrexate is an antimetabolite used to treat rheumatoid arthritis as well as psoriasis and certain types of cancer. Side effects that may go away during treatment include nausea, vomiting, stomach pain, drowsiness, dizziness, mouth sores, diarrhea, fever, fatigue, persistent sore throat, unusual bleeding or bruising, black stools, skin rash, enlarged glands/lymph nodes, dark urine, bone pain, and unusual pain. More serious side effects include yellowing of the eyes or skin, change in the amount of urine, chest pain, dry cough, breathing problems, calf pain or swelling, vision changes, irregular heartbeat, muscle weakness, mental changes, and seizures.
One of the most serious dangers associated with Methotrexate use is overdose. It should only be taken once a week, not once a day. In one case, a doctor prescribed methotrexate to a 79-year-old woman on a daily basis. The woman later died. This prompted the Committee on Safety of Medicines to demand that a new warning statement be added to inform users of the serious risk posed by accidental or purposeful overdose.
Methotrexate was also linked to lung toxicity, or pneumonitis, in early 2003. Symptoms of lung disease include difficulty breathing, heavy coughing, and fever. If you are taking methotrexate and are experiencing any of these symptoms, contact your physician immediately.
Remicade, or Infliximab, is an immune-suppressing drug manufactured by Centocor used to treat rheumatoid arthritis and Crohn’s disease. In 2001, only 3 years after its approval by the FDA, Centocor was forced to add an alarming health risk to its label – using Remicade quadruples the risk of developing tuberculosis (TB). After an analysis of data from 70 reported cases, including at least four fatalities, the FDA concluded that the risk was real and a warning was added to the medication’s label advising doctors to perform a tuberculin skin test on any patient prior to beginning treatment.
The risk of developing TB is especially high with Remicade because it suppresses the immune system which allows latent tuberculosis to become active. (To put things in perspective, about 6.2 cases of TB occur in every 100,000 arthritis sufferers annually. That figure jumps to 24.4 per 100,000 for patients taking Remicade.) Symptoms of tuberculosis include severe cough, chest pain, and weight loss. It can be spread through the air from person to person. If you are currently taking Remicade and are experiencing any of these symptoms, contact your physician immediately.
An additional side effect for Remicade that also pertains to Enbrel is an elevated risk for heart failure after treatment. Although no study has produced conclusive evidence as to the severity or legitimacy of the risk, there has been a suggestion of worse heart failure outcomes in patients who use Enbrel and Remicade. There are already warnings on the drugs’ labels stating that patients with moderate or severe heart failure should not use the drugs.
Enbrel, or entanercept, is an immune response modifier used to reduce the symptoms and slow the progression of RA and psoriatic arthritis. (It is also prescribed for psoriasis). It is intended for moderate to severe cases of RA and is usually prescribed when all other medications have failed to produce satisfactory results. Enbrel is a TNF (tumor necrosis factor) blocker.
Enbrel is administered by injection either by a doctor or by the patient twice each week. Enbrel may take several weeks to start working and stopping it abruptly may be harmful. Minor side effects associated with Enbrel include dizziness and pain, redness, itching, or swelling at injection site. More serious side effects or health risks include infection, persistent sore throat, fever, rash on nose and cheeks, unusual fatigue, easy bruising or bleeding, difficulty breathing, tightness of chest, and outbreak of rash or hives.
Unfortunately, Enbrel also presents the possibility of fatal infections and serious blood reactions and can stimulate nervous system disorders. Immunex Corp., the manufacturer of Enbrel, has warned that patients using Enbrel have been diagnosed with neurological and hematological disorders such as multiple sclerosis, myelitis, and optic neurosis. This cautionary statement was released after reports of ten occurrences of such disorders, including five fatalities, relating to Enbrel usage.
Enbrel, like Remicade, also poses an increased risk of TB. Women taking Enbrel to treat rheumatoid arthritis may be at a special risk for developing symptoms of systemic lupus erythematosus (SLE). It should be discontinued if the patient develops an infection.
Humira, or adalimumab (from Abbott Laboratories), is a recombinant human IgG1 monoclonal antibody and, like Enbrel, is a TNF blocker. Humira is also a drug of last resort for the treatment of moderate to severe RA that has failed to respond to other medications.
This drug is administered by injection (by a doctor or the patient) once every one or two weeks. To be sure, the risks associated with Humira are quite serious. They include:
• Sepsis, or systemic infection (including fatalities);
• certain cancers (malignancies) including lymphomas;
• invasive opportunistic fungal infections.
Certainly, the ravages of moderate or severe RA, psoriatic arthritis, and psoriasis are quite significant. It is therefore understandable that any drug which promises relief from the unrelenting pain, discomfort, disfigurement, and physical limitations associated with these diseases will have a great deal of success despite potentially serious or even fatal side effects. This is simply a fact of life.
Despite this attractiveness, however, one must be objective and decide at what point the benefits of such drugs truly outweigh the risks they present. To be sure, some of the risks are minor and others, though serious, are tolerable in that they are reversible, short-term, or non-life threatening.
Many of the risks, however, are extremely serious. Cancer, lymphoma, TB, fatal infections, liver damage, birth defects, Stevens-Johnson Syndrome, heart attacks, and strokes are difficult to balance against relief from anything but the most severe arthritis-related symptoms. Clearly, for some people the risks may be acceptable. This is especially so if all other therapies have failed and if the pain and crippling effects of RA are no longer tolerable.
While such a decision is an individual one, it should be made only after all other avenues have been explored and with a full understanding of the potential consequences. Websites which contain extensive information about all of these drugs are: www.webmd.com, www.rxlist.com, www.drugs.com, and www.fda.gov. In addition, Parker & Waichman provides separate web pages at www.yourlawyer.com for over 60 drugs and supplements with potentially dangerous side effects.
If you believe that you or a loved one has been injured by any pharmaceutical product, please contact Parker & Waichman for a free consultation. You may also submit a new case inquiry (case evaluation) directly through our website.