Choosing a<unk>  for people with special considerations Condition Commonly recommended<unk> s Explanation Kidney transplantation recipients taking ciclosporin Pravastatin or fluvastatin Drug interactions are possible, but studies have not shown that these<unk> s increase exposure to ciclosporin. HIV-positive people taking protease inhibitors Atorvastatin, pravastatin or fluvastatin Negative interactions are more likely with other choices Persons taking gemfibrozil, a non-statin lipid-lowering drug Atorvastatin Combining gemfibrozil and a<unk>  increases risk of rhabdomyolysis and subsequently kidney failure Persons taking the anticoagulant warfarin Any<unk>  The<unk>  use may require that the warfarin dose be changed, as some<unk> s increase the effect of warfarin. The most important adverse side effects are muscle problems, an increased risk of diabetes mellitus, and increased liver enzymes in the blood due to liver damage. Over 5 years of treatment<unk> s result in 75 cases of diabetes, 7.5 cases of bleeding stroke, and 5 cases of muscle damage per 10,000 people treated. This could be due to the<unk> s inhibiting the enzyme (HMG-CoA reductase), which is necessary to make cholesterol, but also for other processes, such as CoQ10 production, which is important for muscle function and sugar regulation. Other possible adverse effects include neuropathy, pancreatic and liver dysfunction, and sexual dysfunction. The rate at which such events occur has been widely debated, in part because the risk/benefit ratio of<unk> s in low-risk populations is highly dependent on the rate of adverse events. A Cochrane meta-analysis of<unk>  clinical trials in primary prevention found no evidence of excess adverse events among those treated with<unk> s compared to placebo. Another meta-analysis found a 39% increase in adverse events in<unk>  treated people relative to those receiving placebo, but no increase in serious adverse events. The author of one study argued that adverse events are more common in clinical practice than in randomized clinical trials. A systematic review concluded that while clinical trial meta-analyses underestimate the rate of muscle pain associated with<unk>  use, the rates of rhabdomyolysis are still "reassuringly low" and similar to those seen in clinical trials (about 1–2 per 10,000 person years). Another systematic review from the International Centre for Circulatory Health of the National Heart and Lung Institute in London concluded that only a small fraction of side effects reported by people on<unk> s are actually attributable to the<unk> . Cognitive effects Multiple systematic reviews and meta-analyses have concluded that the available evidence does not support an association between<unk>  use and cognitive decline.<unk> s have been shown to decrease the risk of dementia, Alzheimer's disease, and improve cognitive impairment in some cases. Additionally, both the Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study and the Health Protection Study (HPS) demonstrated that simvastatin and pravastatin did not affect cognition for patients with risk factors for, or a history of, vascular diseases. There are reports of reversible cognitive impairment with<unk> s. The U.S. Food and Drug Administration (FDA) package insert on<unk> s includes a warning about the potential for non-serious and reversible cognitive side effects with the medication (memory loss, confusion). Muscles In observational studies 10–15% of people who take<unk> s experience muscle problems; in most cases these consist of muscle pain. These rates, which are much higher than those seen in randomized clinical trials have been the topic of extensive debate and discussion. Muscle and other symptoms often cause patients to stop taking a<unk> . This is known as<unk>  intolerance. A recent randomized controlled trial (RCT) gave<unk> -intolerant patients a<unk>  or a placebo inside capsules that looked the same, making the study double-blind – participants did not know which they were taking in any period,<unk>  or placebo. This was repeated 3 times, so there were 6 periods in random order. Patients were queried about their symptoms, which were similar on the<unk>  and on the placebo, showing that<unk>  intolerance depends on people knowing they're taking a<unk> . A smaller double-blind RCT obtained similar results. After being shown their symptom scores, the majority of participants in these 2 studies intended to restart<unk>  treatment. The results of these studies help explain why<unk>  symptom rates in observational studies are so much higher than in double-blind RCTs. The difference results from the nocebo effect, which is the opposite of the placebo effect: the symptoms are caused by expectations of harm. Media reporting on<unk> s is often negative, and patient leaflets inform patients that rare but potentially serious muscle problems can occur during<unk>  treatment. These create expectations of harm. Nocebo symptoms are real and bothersome and are a major barrier to treatment. Because of this, many people stop taking<unk> s, which have been proven in numerous large-scale RCTs to reduce heart attacks, stroke, and deaths – as long as people continue to take them. Serious muscle problems such as rhabdomyolysis (destruction of muscle cells) and<unk> -associated autoimmune myopathy occur in less than 0.1% of treated people. Rhabdomyolysis can in turn result in life-threatening kidney injury. The risk of<unk> -induced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. Coenzyme Q10 (ubiquinone) levels are decreased in<unk>  use; CoQ10 supplements are sometimes used to treat<unk> -associated myopathy, though evidence of their efficacy is lacking . The gene SLCO1B1 (Solute carrier organic anion transporter family member 1B1) codes for an organic anion-transporting polypeptide that is involved in the regulation of the absorption of<unk> s. A common variation in this gene was found in 2008 to significantly increase the risk of myopathy. Records exist of over 250,000 people treated from 1998 to 2001 with the<unk>  drugs atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. The incidence of rhabdomyolysis was 0.44 per 10,000 patients treated with<unk> s other than cerivastatin. However, the risk was over 10-fold greater if cerivastatin was used, or if the standard<unk> s (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) were combined with a fibrate (fenofibrate or gemfibrozil) treatment. Cerivastatin was withdrawn by its manufacturer in 2001. Some researchers have suggested hydrophilic<unk> s, such as fluvastatin, rosuvastatin, and pravastatin, are less toxic than lipophilic<unk> s, such as atorvastatin, lovastatin, and simvastatin, but other studies have not found a connection. Lovastatin induces the expression of gene atrogin-1, which is believed to be responsible in promoting muscle fiber damage. Tendon rupture does not appear to occur. Diabetes The relationship between<unk>  use and risk of developing diabetes remains unclear and the results of reviews are mixed. Higher doses have a greater effect, but the decrease in cardiovascular disease outweighs the risk of developing diabetes. Use in postmenopausal women is associated with an increased risk for diabetes. The exact mechanism responsible for the possible increased risk of diabetes mellitus associated with<unk>  use is unclear. However, recent findings have indicated the inhibition of HMGCoAR as a key mechanism.<unk> s are thought to decrease cells' uptake of glucose from the bloodstream in response to the hormone insulin. One way this is thought to occur is by interfering with cholesterol synthesis which is necessary for the production of certain proteins responsible for glucose uptake into cells such as GLUT1. Cancer Several meta-analyses have found no increased risk of cancer, and some meta-analyses have found a reduced risk. Specifically,<unk> s may reduce the risk of esophageal cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, and possibly prostate cancer. They appear to have no effect on the risk of lung cancer, kidney cancer, breast cancer, pancreatic cancer, or bladder cancer. Drug interactions Combining any<unk>  with a fibrate or niacin (other categories of lipid-lowering drugs) increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years. Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose<unk> s or in those on<unk> /fibrate combinations, and mandatory in the case of muscle cramps or of deterioration in kidney function. Consumption of grapefruit or grapefruit juice inhibits the metabolism of certain<unk> s. Bitter oranges may have a similar effect. Furanocoumarins in grapefruit juice (i.e. bergamottin and dihydroxybergamottin) inhibit the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism of most<unk> s (however, it is a major inhibitor of only lovastatin, simvastatin, and to a lesser degree, atorvastatin) and some other medications (flavonoids (i.e. naringin) were thought to be responsible). This increases the levels of the<unk> , increasing the risk of dose-related adverse effects (including myopathy/rhabdomyolysis). The absolute prohibition of grapefruit juice consumption for users of some<unk> s is controversial. The U.S. Food and Drug Administration (FDA) notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain<unk>  drugs. Protease inhibitors and<unk> s taken together may increase the blood levels of<unk> s and increase the risk for muscle injury (myopathy). The most serious form of myopathy, rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal. Osteoporosis and fractures Studies have found that the use of<unk> s may protect against getting osteoporosis and fractures or may induce osteoporosis and fractures. A cross-sectional retrospective analysis of the entire Austrian population found that the risk of getting
Statin
Anisatin
Arbekacin
Pitavastatin
Cortistatin 
Petroleum jelly
Anthopleurin
Clitoraid