Drug Profile

Fluvastatin is a member of the statin family of cholesterol-lowering drugs. This statin drug works by inhibiting an enzyme that is responsible for the production of cholesterol in the body.

Fluvastatin is approved by the Food and Drug Administration (FDA) to lower cholesterol. This statin also can be used in patients with coronary heart disease to reduce the chance of undergoing coronary revascularization procedures (procedures to open blocked heart arteries) such as angioplasty and stent placement or heart bypass surgery.[2] Reducing the chance of undergoing a coronary revascularization procedure is not the same as reducing the risk of a heart attack or stroke.

Because fluvastatin has not been shown to reduce the risk of heart attack or stroke, we recommend that patients DO NOT USE this drug. In contrast, the manufacturers of pravastatin (PRAVACHOL), simvastatin (ZOCOR), lovastatin (MEVACOR) and atorvastatin (LIPITOR) can make health claims of reducing the risk of heart attack and/or stroke because they have conducted studies demonstrating these benefits. We recommend that patients with a history of heart disease, stroke and diabetes instead use one of these four statin drugs to lower their cholesterol.

Adverse effects

Drug-induced muscle injury, or rhabdomyolysis, is a known adverse effect of all statin cholesterol-lowering drugs. Rhabdomyolysis is usually accompanied by pain, tenderness and weakness in the affected muscles. The most important consequences of rhabdomyolysis, however, are not those on the muscles themselves. As muscle cells break down, they release substances that can cause injury to the kidneys that is sometimes permanent but, even when reversible, sometimes requires temporary hemodialysis (mechanical filtering of the blood). If muscle cells break down rapidly enough, released potassium can cause lethal heart rhythm disturbances. A number of drugs can interact with the statin drugs in ways that can increase the likelihood of drug-induced muscle injury. See the "Interactions with Other Drugs" section.

Cases of fatal rhabdomyolysis led to the withdrawal of the statin drug cerivastatin (BAYCOL) in August 2001.[3] Rosuvastatin (CRESTOR) is also listed as a Do Not Use drug because of cases of rhabdomyolysis and kidney toxicity seen in clinical trials before the drug was approved.

Liver toxicity is another potential problem with the statin drugs. The current labeling for these drugs states that elevations in liver function tests, an early indication of possible liver toxicity, have been seen with the use of statins. The labeling also warns, “It is recommended that liver function tests be performed prior to and at 12 weeks following initiation of therapy or the elevation of dose.” No mention is made of possible liver failure.

The FDA undertook an evaluation of reports of potential liver failure associated with the use of the statin drugs in May 2000. A total of 90 cases of liver failure had been reported to the FDA for the six statin drugs on the market at the time. Of the 90 cases, 62 were consistent with the FDA’s definition of liver failure and more than half of these 62 patients died.[4]

The statin drugs seem to share psychiatric risks with other cholesterol-lowering drugs. Aggressive behavior; memory impairment; mood changes; and cognitive, sleep and perception disorders, such as nightmares, have been reported with the use of many drugs used to treat high cholesterol: the statins, fenofibrate (TRICOR), gemfibrozil (LOPID), ezetimibe (ZETIA) and clofibrate (ATROMID-S).[5],[6] Though researchers have not yet established a direct link between these reports and the use of the cholesterol-lowering drugs listed, patients should be alert to this possibility and report unexpected changes to their doctors. Statin-induced memory impairment could be mistaken for other conditions such as early Alzheimer’s disease. This could result in the prescribing of a drug to treat Alzheimer’s when it is not needed.[7]

In addition to the adverse effects listed above, there is also an association between the long-term use of statins and an increased, although rare, risk of neuropathy (damage to the nervous system). This can take the form of decreased or increased sensation, abnormal sensation (pins and needles) or muscle weakness. In the majority of cases, the symptoms improved upon cessation of the drug.[8]

Risk of increased blood sugar levels and diabetes

In January 2013, Health Canada, an agency similar to the FDA, issued a communication to the public concerning the use of the statin drug class and the risk of increased blood sugar levels in patients with a pre-existing risk for diabetes. Close monitoring for diabetes is recommended in these patients when using statins.[9]

Studies say…

In 2010, there were 11 reports of tendinitis and 10 reports of tendon rupture associated with statin drug therapy that were reported to the Netherlands Pharmacovigilance Centre Lareb. Tendinitis occurs when the tendon — fibers that join the muscles to the bone — becomes inflamed. Tendon rupture occurs when the tendon is torn.[10]

The Canadian Adverse Reactions Newsletter published an article in its October 2011 issue concerning the use of statin drug therapy and the occurrence of interstitial lung disease (ILD), a group of lung disorders that affects breathing. The article stated that “As of Mar. 31, 2010, Health Canada received 8 adverse reaction (AR) reports of ILD, or pathologies associated with ILD.” These cases were suspected to be associated with statin drug use.[11]

In June 2012, the Archives of Internal Medicine published an article concerning the use of statins in women. The information in the article was a meta-analysis of previously published studies on the use of statins in women. The meta-analysis revealed two major findings: First, the benefits of statins were significant for all outcomes in men, a result consistent with previously published results. Second, while there was a statistically significant risk reduction in both men and women for coronary mortality, heart attack (fatal and nonfatal) and cardiac intervention, there was “no statistically significant risk reduction for women taking statins compared with women taking placebo for the reduction of all-cause mortality [death from any cause] and any type of stroke.”[12]

In 2012, a study was conducted reviewing muscle and tendon adverse events reported to the FDA Adverse Event Reporting System associated with statin drug use. The data studied in these post-marketing case reports showed that adverse events reported varied for the different drugs in the statin drug class. The drugs reviewed in the study were atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin and fluvastatin. The study data examined the relative potency of each drug along with its muscle-related adverse events risk. The results of the study found that rosuvastatin had the highest relative risk of adverse events, atorvastatin and simvastatin had an intermediate risk, pravastatin and lovastatin had the lowest risk, and fluvastatin was “an apparent exception.” (For a detailed description of adverse events reported for each drug, see the referenced article.)[13]

In 2013 the Annals of Internal Medicine published an article on the co-administration of statins (atorvastatin, lovastatin and simvastatin) with macrolide antibiotics (clarithromycin, erythromycin and azithromycin) in patients older than 65 years. The data reviewed showed that patients using atorvastatin, lovastatin or simvastatin experienced statin drug toxicity with co-administration of clarithromycin or erythromycin.[14]

The British Medical Journal published an article in May 2013 in which it studied the risk of new-onset diabetes in patients treated with statin drugs. The study analyzed the results of patients treated with atorvastatin, simvastatin or rosuvastatin, compared with patients treated with pravastatin, and their risk of new-onset diabetes. The results of the study data found that patients treated with atorvastatin, simvastatin or rosuvastatin had a higher risk of new-onset diabetes. The study also stated that patients treated with lovastatin and fluvastatin did not show this increased risk.[15]

An article published in 2015 in Diabetologia showed that patients using statins had a 46 percent increase in the risk of type 2 diabetes.[16]

In 2016, the American Journal of Cardiovascular Drugs published an article showing that statin drugs were associated with an increased risk of developing diabetes.[17]

In 2018, the Journal of the American Medical Association Internal Medicine (JAMA Internal Medicine) published an article showing that statins are associated with a rare but potentially disabling autoimmune muscle disorder known as idiopathic inflammatory myositis.[18]

With more than 200 million prescriptions each year in the U.S., statins are one of the most prescribed drug categories here and in much of the world (at least in so-called developed countries). Yet about two-thirds of statins are not prescribed for secondary prevention but for primary prevention — that is, to prevent people who have not previously had heart attacks, strokes or other cardiovascular disease from developing such diseases. Over the past decade, especially in the last several years, a number of published studies and reviews have documented the overprescribing of statins for primary prevention, especially for those whose combination of age, medical history, cholesterol levels and other cardiovascular risk factors place them at the lower end of the scale of risk for first-time cardiovascular events. This research has raised serious questions regarding the need for any pharmacological intervention in these lower-risk people. Unfortunately, this majority of statin users are subjected to the risks of these drugs without benefits.

Regulatory actions surrounding fluvastatin

2005: In March the FDA denied two citizen’s petitions that would have required the professional product labeling for the cholesterol-lowering statin drugs to recommend that the dietary supplement coenzyme Q10 be added to statins to reduce the risk of muscle damage, heart damage and congestive heart failure. They found that there was not significant evidence to suggest that coenzyme Q10 levels are responsible for the adverse effects associated with statin use or that supplementation with coenzyme Q10 has any impact on preventing or lessening any of the potential adverse effects of the statin drugs.[19]

2012: In February, the FDA issued information concerning safety changes for statins. These changes include the removal of routine monitoring of liver enzymes from the drug product information and the addition of information about potential, generally nonserious and reversible cognitive adverse effects, as well as reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels.

Safety changes also were added for lovastatin concerning contraindications and dose limitations when lovastatin is taken with certain medicines that can increase the risk of muscle injury.[20]

In March, the FDA issued an advisory concerning interactions between protease inhibitors and certain statin drugs. HIV or HCV protease inhibitors, when used with statins, may raise the levels of statins in the blood and increase the risk of muscle injury (myopathy).[21]

2013: The FDA updated the drug product label for statins to include information on rare reports of an autoimmune myopathy associated with use of such drugs. Immune-mediated necrotizing myopathy presents with proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of treatment with statins.[22]