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CHOLESTEROL DRUGS: THE RISKS VARY AS WIDELY AS THE CHOICES Part 1 - The StatinsNov 1, 2004 Introduction:
Although more people worldwide suffer from high cholesterol than ever before, the problem has reached epidemic proportions in the United States. Fast food, junk food, exceptionally large portions, poor eating habits, misleading or inadequate labeling, and lack of exercise, among other things, have produced the highest percentage of overweight Americans in history. Morbidly obese men, women, and even children are no longer oddities, they are commonplace.
In addition, many foods now contain high amounts of saturated fat and/or trans fatty acids. Trans fatty acids are found in many foods such as packaged cookies, crackers, and snacks, commercially fried fast food, vegetable shortening, and some margarine. Packaged goods containing "partially-hydrogenated vegetable oils" or "shortening" probably contain trans fats.
Before the advent of trans fatty acids, foods were cooked in or with lard, palm oil, butter, or other substances high in saturated fats. Saturated fats increase LDL (bad) cholesterol and are associated with an increased risk of heart disease. As a result, manufacturers and restaurants started using vegetable oils in their food production. Since liquid vegetable oils are not stable to heat and spoil easily, the process of "hydrogenation" is used to stabilize the liquid oils in food production and to increase their shelf life. The process of hydrogenation causes the formation of trans fatty acids.
Unfortunately, it has been discovered that trans fatty acids also increase LDL (bad) cholesterol and lower HDL (good) cholesterol and, thus, also create an increased risk of heart disease. There have been some studies that have shown a diet high in trans fatty acids may also be linked to a greater risk of Type 2 Diabetes.
Untreated levels of high LDL cholesterol are, therefore, a very serious public health problem which is associated with a number of serious medical problems some of which are life-threatening.
Not surprisingly, pharmaceutical manufacturers quickly discovered that there was a vast market for prescription drugs that would help lower cholesterol. This has led to the development of several cholesterol medications. Some of these drugs are better than others, some are safer than others, and some even have beneficial secondary effects. Others, however, are extremely dangerous and all of them need to be carefully monitored.
The medications which are currently available fall into a number of categories or classes. These include (chemical names – the brand names will be given in the actual discussion of each drug):
* Resins (cholestyramine, colesevelam, and colestipol)
* Fibrates (bezafibrate, clofibrate, penofibrate, and gemfibrozil)
* Statins (atorvastatin, fluvastatin, itavastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin)
In this month’s Newsletter we will be discussing the “statins.” Next month we will cover the remaining medications.
The statins consist of eight brand name drugs in seven sub-categories. Mevacor, Altocor, and Advicor (lovastatin), Pravachol (pravastatin), Zocor (simvastatin), Lescol (fluvastatin), Lipitor (atorvastatin), Crestor (rosuvastatin), and Baycol (cerivastatin) (withdrawn from the market in August 2001).
Many people, especially those with high cholesterol, have come to see all cholesterol as “bad,” yet cholesterol is needed to form important hormones and perform other vital cell functions. The truly “bad” cholesterol is known as low-density lipoprotein (LDL) and it clogs arteries. “Good” cholesterol, or high-density lipoprotein (HDL), however, works like a drain cleaner for arteries.
Statin drugs work by inhibiting HMG CoA, an enzyme that enables the liver to make cholesterol. When the liver cannot produce its own cholesterol, it removes it from the blood. This causes blood levels of cholesterol to fall which in turn decreases the risk of clogged arteries. Statins are designed to reduce LDL levels yet, for many people; their HDL levels can rise while taking a statin drug.
For all the good they were supposed to do, statin drugs have been quite problematic for those taking them. While some side effects of statins are mild, they have been responsible for causing severe muscle breakdown known as rhabdomyolysis, liver disorder, kidney failure, and death.
Of the seven statins mentioned above, the worst of the lot are Baycol and Crestor. Baycol was removed from the market in August of 2001 and Crestor may soon be on its way to the prescription drug graveyard since it has already gained the reputation of being “new but more dangerous.”
Although this drug has been removed from the market, it was taken by millions of people for significant periods of time. Thus, we wish to inform our readers about it in the event that one or more of them (or a loved one) has suffered a serious adverse affect as a result of taking Baycol.
Baycol, a statin drug manufactured by Bayer and GlaxoSmithKline, is currently the only cholesterol-lowering drug to be withdrawn from the market because of adverse effects. On August 8, 2001, the Bayer Pharmaceutical Division announced Baycol was being removed from the U.S. market because of reports of an adverse reaction of rhabdomyolysis (rhabdo), but by that point at least 6 million people worldwide had taken the drug.
Rhabdomyolysis is a muscle disease which causes kidney injury. It is categorized by the destruction of muscle cells which are subsequently released into the bloodstream. Symptoms of rhabdo include isolated or generalized muscle pain, weakness, tenderness, fatigue, malaise, fever, dark urine, nausea, and vomiting.
All drugs in the statin group have been linked to reports of rhabdo, but Baycol has been responsible for more fatal cases of the muscle disease. Before taking Baycol off the market, the FDA received reports of more than 50 rhabdo-related deaths among Baycol users worldwide. The fatal cases primarily involved elderly patients, interactions with other prescription drugs, and higher dosages. Even after the drug was finally removed, fatalities continued to climb to more than 100.
After Baycol was pulled off the market, numerous lawsuits were filed by people injured by the drug. 3,500 lawsuits were filed and 2,825 claims were settled for a total of $1.08 billion. During that litigation, it was discovered that Bayer and GlaxoSmithKline knew of the harmful effects of Baycol before its release in 1997. In fact, memos from Bayer’s safety officials in 1999 revealed that its staff was struggling to respond to the growing number of patients who developed rhabdo. While the risk of rhabdo was described in the drug’s warning label, Bayer may not have conducted an appropriate amount of research to determine just how severe the risk was and what was necessary to prevent this risk from becoming fatal. In order to avoid having to report negative data to the FDA, Bayer did not do a sufficient amount of testing regarding the higher dosage, 0.8mg pills.
The Baycol situation is disturbing for several reasons. It serves as a reminder that drugs are often rushed to market (“fast tracked”) without adequate testing and research. In fact, the majority of drugs that are recalled are recalled within their first 5 years on the market. This proves that longitudinal testing is often absent and therefore long-term effects of certain drugs are never revealed until it is too late. (The recent Vioxx debacle is another example of this serious problem). Even in situations where drugs are properly tested, there is no guarantee that negative results will force a manufacturer to withdraw it from the market. Many drugs are being released and kept on the market despite evidence of serious side effects. Such decisions are usually motivated by financial considerations since a successful drug can often generation billions of dollars in annual revenue.
Crestor, another statin drug, is already following in Baycol’s footsteps and seems doomed to a similar fate. After reports of kidney damage and muscle weakness, a precursor to rhabdo, AstraZeneca abruptly stopped ongoing clinical trials for Crestor involving patients taking 80 milligrams per day. Crestor has been listed by Public Citizen as a “DO NOT USE” drug because, like Lipitor and Lescor, it has not demonstrated a significant health benefit in terms of lowering cholesterol and minimizing the risk of heart attack or stroke. Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, has gone on record as stating: “It becomes clearer by the day that this drug is uniquely toxic, but offers no unique benefit and must be removed from the market.”
AstraZeneca, however, has countered the medical and scientific evidence of the drug’s dangers with an expensive direct to consumer marketing campaign featuring actor Patrick Stewart (Captain Jean-Luc Picard of Star Trek: The Next Generation). Thus, Crestor, like all too many other dangerous drugs, remains a “cash cow” because of creative marketing and not because it is a safe and effective treatment for the medical condition it was designed to alleviate.
Crestor has been labeled particularly dangerous because of the threat of kidney toxicity in addition to rhabdo, a relatively common side effect connected to statin usage. Unlike other statins, however, Crestor causes abnormal elevations in urine protein and blood, both of which are indicators of severe kidney toxicity. While other statins have been responsible for sporadic cases of rhabdo, Crestor is the only statin that has revealed the potential for life-threatening rhabdo development prior to FDA approval. As reported in PharmaLive: “The FDA had evidence before approving the cholesterol drug Crestor that it caused an increased incidence of rhabdomyolysis (severe muscle deterioration), yet the agency approved it anyway, erroneously believing that this toxicity was limited to an 80 milligram dose that was not ultimately approved.”
The warning label for all statin drugs, including Crestor, indicates that liver function tests are recommended both before and 12 weeks after beginning treatment or changing dosage. Periodic tests are recommended for as long as treatment continues. Rhabdo is also mentioned as a rare side effect as is acute renal failure. Rare or not, however, these side effects need to be taken seriously as they are potentially fatal.
Public Citizen’s Health Research Group believes that the FDA should have required routine urine testing for Crestor patients taking both available dosages as this would reveal traces of protein, an indicator of kidney problems. In a letter to the FDA dated October 29, 2004, the organization has petitioned for the drug to be taken off the market. (Public Citizen made a similar petition in March, 2003).
As of now, regular urine testing is only required for people who have diabetes or are pregnant. Urine testing is just one way in which treatment should be continually and closely monitored. Ongoing monitoring by a physician is perhaps the only way to catch serious medical problems before they become fatal.
Cases of serious Crestor-related side effects began surfacing even before the drug was released on the global market. (As reported in PharmaLive: “The rate of reports of kidney failure or damage among patients taking the cholesterol drug Crestor is 75 times higher than in all patients taking all other statins, according to a Public Citizen analysis of government data.”) The reports of 65 Crestor-related cases of rhabdomyolysis in the United States is a rate approaching that of Baycol which was taken off the market for that very reason. As a result, two major U.S. insurance companies, WellPoint, and Group Health Cooperative of Puget Sound, have refused to reimburse for Crestor citing Baycol as a precursor.
Pravachol and Lipitor
Pravachol, another member of the statin family manufactured by Bristol-Meyers Squibb, has been connected to rhabdo as well as liver and kidney problems. Other side effects include difficulty breathing, closing of the throat, swelling of the face, hives, decreased urine or rust-colored urine, blurred vision, gas, bloating, nausea, heartburn, abdominal pain, constipation, diarrhea, coughing, headache, and insomnia. Any of these side effects can be indicators for more serious health problems.
Lipitor, manufactured by Pfizer, is one of the well-known statins and is widely advertised on television and in periodicals. Warning labels for Lipitor indicate the risk for rhabdo and kidney failure as the two most serious side effects with gas, constipation, heartburn, and stomach pain as the less serious side effects. Lipitor, like all statins, is not recommended for use by pregnant women or people with pre-existing liver problems.
In a study comparing the benefits of Pravachol and Lipitor, Pravachol proved to be inferior. In those patients taking Pravachol, arthrosclerosis worsened during the 18-month treatment period. Despite these findings, however, Pravachol is still being prescribed to patients looking to lower their cholesterol.
Dr. Steven Nissen, an eminent cardiologist at the Cleveland Clinic who directed the study of 502 patients, said that while he had changed his practices based on the findings of the study, he would not force his decision on any of his colleagues and leave them to make their own minds up. However, if a uniform system for prescription drug distribution by physicians is not adopted, some conscientious doctors may choose to stop prescribing a drug which has been deemed harmful while others may continue to promote it.
Pravachol should not be taken by anyone with liver disease. It also should not be used to lower high cholesterol that stems from medical conditions such as alcoholism, poorly controlled diabetes, an under active thyroid, or kidney problems. Pravachol may have significant interactions with other drugs such as: Questran, Tagamet, Colestid, Cardizem, Dilacor, Tiazac, Sandimmune, Neoral, Erythromycin, Lopid, Sopranox, Niacor, Niaspan, and Coumadin. There is also some suspicion that Pravachol may cause birth defects and so it should not be taken by pregnant women. It should also not be prescribed to women who are breastfeeding.
Lipitor should not be taken by anyone with liver disease or during pregnancy or while breastfeeding. Serious drug interactions may occur if Lipitor is taken with: Antacids such as Maalox TC Suspension, Atromid-S, Colestid, Sandimmune, Neoral, Digoxin, Lanoxin, immune system suppressors, Erythromycin, Tricor, Diflucan, Lopid, Sporanox, Nizoral, Niaspan, Niacor, Slo-Niacin, and oral contraceptives.
Zocor, which is marketed by Merck, has become one of the more popular statins as it is widely advertised on television and in periodicals. While some side effects such as pain or weakness, liver complications, and harmful drug interactions do exist, Zocor is promoted as being “a cholesterol medication proven to significantly reduce the risk of heart attack and stroke in people with heart disease or diabetes – regardless of cholesterol level.” This may be one benefit to Zocor but new dangers were discovered in 2002.
In July of 2002, Merck was forced to revise the warning label for Zocor to include information about the potential risk for developing myopathy and rhabdo from taking the drug alone or in combination with other medicines. Again, this is a persistent problem for all statins and while some may have benefits that seem to place them at a level above the rest, the risk for these muscle illnesses should not be overlooked. A spokesperson for Merck said that the new FDA-required warning adds clarity but does not change the pre-established safety and “efficacy” of Zocor.
Zocor should be discontinued before major surgical procedures. Its interaction with certain other drugs must be carefully monitored. For example: Zocor tends to enhance the effects of Coumadin and Lanoxin. It also increases the chance of muscle damage when combined with: Cordarone, Biaxin, Atromid-S, Sandimmune, Neoral, Erythromycin, Tricor, Lopid, Sporanox, Nizoral, Serzone, Niaspan, Protease inhibitors (used in treatment of HIV), Calan. Zocor may also cause serious problems when combined with significant quantities of grapefruit juice. Zocor should be avoided by women who are pregnant or breastfeeding.
Lescol is available in standard capsules and extended-release tablets (Lescol XL). As with all statins, liver damage is a possibility. Thus, liver enzyme levels should be tested on a regular basis. Signs of damage to muscle tissue should also be reported immediately. Serious drug interactions may occur when Lescol is taken with: Questran, Tagamet, Atromid-S, Sandimmune, Neoral, Voltaren, Lanoxin, Lanoxicaps, Erythromycin, Lopid, Micronase, Niaspan, Prilosec, Dilantin, Zantac, and Rifadin. Lescol should not be taken by women who are pregnant or breastfeeding.
Lovastatin (Altocor, Mevacor, and Advicor)
These three drugs are essentially the same. Mevacor is the “standard” form of lovastatin, Altocor is an extended-release form of the drug, and Advicor is Mevacor combined with extended-release Niacin.
Again, since the various forms of lovastatin are members of the statin class of drugs, liver and muscle tissue damage are possible side effects. Women who are pregnant or breastfeeding should avoid the drug as should those with liver disease. Altocor is not recommended for people below the age of 20. Advicor is not recommended for children. Mevacor may be prescribed for children between 10 and 17 but only if introduced in intervals of 4 weeks or more and in girls who have been menstruating for at least one year. The safety and effectiveness of Mevacor has not been studied in children under 10 or in children of any age in doses larger than 40 milligrams per day.
Lovastatin taken with large quantities of grapefruit juice may cause serious problems and should not be combined with certain other drugs such as: Antipyrine, Coumadin, Dicumarol, Tagamret, Diflucan, Blaxin, Sandimmune, Neoral, Erythromycin, Lopid, HIV protease inhibitors, Sporanox, Nizoral, Aldactone, Serzone, Niaspan, Niacor, Calan, and Verelan.
Statins, as a group of drugs, are often an acceptable solution for people who have undergone a long and arduous battle with cholesterol maintenance. Although the drugs do have potentially serious side effects, such problems are usually avoidable with careful medical monitoring and by patients being thoroughly aware of the warning signs associated with those side effects. Patient awareness cannot be overemphasized. The key is for all patients taking any of the statins to ask questions, read the product information, be aware of potential drug and food interactions, follow dosage and other instructions carefully, and make every effort to follow a proper and healthy diet and exercise plan. We also strongly urge all potential statin users to avoid the more risky drugs such as Crestor and Pravachol.
In addition to the aforementioned side effects relating to specific statins, the following information should be taken into account as it relates to most or all statins.
* Statin drugs such as Lipitor, Zocor, Pravachol, Crestor, Lescol, Mevacor, and Baycol may be linked to birth defects. These drugs may cause severe central nervous system defects and limb deformities when used within the first trimester of pregnancy. These are the types of problems which can be expected when the embryo does not get enough cholesterol during the early stages of pregnancy.
* Young people are specifically at risk for developing ailments associated with the statins as the drugs’ effects on that age group are not yet well understood. Patients age 45 and under have been the least studied age group in terms of statin use. Statins have been prescribed to younger men and women in response to the growing realization that high cholesterol early in life can lead to life-threatening cardiovascular consequences later on.
* Statins can cause nerve damage, or polyneuropathy, in extremely rare circumstances. A Danish physician noticed this side effect in 14 statin patients. This has not been listed as a primary side effect because of its rarity.
* Statins have been linked to memory loss following the outcome of a study at University of California at San Diego. Cholesterol, which is related to heart disease, is also an essential organic molecule in the brain. Some researchers have postulated that if cholesterol production is blocked, such as when statins enter the body, it can interfere with the brain’s performance and cause memory loss. Risk factors of memory problems are heart disease and stroke. More research is being conducted on this matter.
* One very vocal lung cancer sufferer believes his long-term use of Lipitor played a role in his development of that disease. He has carefully analyzed animal testing data which suggests that the statins may be the most carcinogenic drugs ever approved for wide scale human consumption. (Significantly, lab animals were exposed to dosages on the order of those prescribed to humans). He also claims that this grave side effect has been “missed” because it is so long-term, possibly up to 20 years. His story and links to additional material relating to the cancer study can be found at http://www.captainclark.com/Pages/lipitorhorror.html.
If you believe that you or a loved one has been injured any of the statin drugs, contact Parker & Waichman immediately for a free case evaluation. You may also visit our website at www.yourlawyer.com for additional information and news concerning these drugs and others which have potentially serious side effects.