The evidence that cholesterol medication is sending you to knee replacement – Caring Medical Florida

Marion Hauser, MS, RD

High cholesterol, and its treatment with statins, have been a hallmark of cardiovascular disease management for decades. Many people worry about their cholesterol because they feel they have to, based on drug companies and the media bombarding us with the impression there is a one to one linkage between elevated blood fats and arteriosclerosis. The benefits, side effects, and even the worthiness of taking statins have been under constant attack in recent years. One of the side-effects reports, statins’ negative influence on soft tissue, namely tendons and ligaments, will be the focus of this article.

Researchers writing in the medical journal Knee Surgery, Sports Traumatology, Arthroscopy, (1) discussed the accumulating clinical evidence indicating the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use.

In their experimental study, the researchers designed a plan to evaluate and compare the biomechanical and histopathological (tissue-damaging) effects of the three most commonly prescribed statins (simvastatin, atorvastatin, and rosuvastatin) on the Achilles tendon in rats.

Statins were given to the rats at daily doses of 20 and 40 mg/kg for 3 weeks. One week later, the Achilles’ tendons were dissected and their biomechanical properties, including ultimate tensile force, yield force, and elastic modulus, were determined.

• All the statins caused deterioration of the biomechanical parameters of the Achilles tendon. Histopathological (tissue damage) analysis demonstrated foci of dystrophic calcification (the calcification of dead and dying soft tissue) in the statin-treated groups.

Higher doses of either of these two statins are toxic for tendon fibroblasts

Researcher Pernilla Eliasson who is affiliated with the University of Copenhagen, Linköping University, Sweden, and the University of Rochester in New York lead a team of researchers looking at the complexity of Simvastatin and atorvastatin and its relationship with tendon damage.

The research appearing in the online medical journal PLOS (2) examined the theory that Simvastatin and atorvastatin may have different potential for negative effects on tendons. Atorvastatin has been pointed out as one of the most harmful statins for tendon tissue while simvastatin has appeared with mixed findings.

• Some studies indicate that simvastatin has a negative impact on tendon tissue, while other studies suggest that simvastatin might even have a positive effect.
• Both atorvastatin and simvastatin had a negative effect on the tendon constructs in our study, however, the effect of simvastatin was in fact stronger and more pronounced.
  • This indicates that simvastatin indeed is harmful to tendon tissue and its extracellular matrix. However, high dose atorvastatin treatment was the only treatment that had an effect on collagen content, and this was reduced by 22% compared to controls.
• Simvastatin had no effect on the collagen content to the researcher’s surprise. This indicates that there might be some differences in the mechanism of action on human tendon cells and extracellular matrix between these two statins. The range of the dosage of the two statins in clinical settings is similar, though the average dose for atorvastatin is slightly lower than the average dose for simvastatin.

Higher doses of either of these two statins are toxic for tendon fibroblasts

The researchers concluded that normal statin treatment of just seven days had such a detrimental effect upon tendon tissue indicates that also long-term adaptations may occur. The more you take the statins, the worse the tendon damage.

Soon after taking these new cholesterol medications, I felt a sharp and sudden pain in my knee

A patient comes in on a recommendation from a friend.

“I am here because I have very bad knee pain . . . here is my story:

I went to the doctor for my check-up. My blood work revealed slightly elevated cholesterol and I was advised that I need to take and was given prescriptions for medications that would lower my cholesterol. I also told my doctor that my knee was hurting, could I get something for it? My doctor asked, when and how the knee pain started? I said I aggravated it with a new exercise program, one I would hope that would lower my weight and cholesterol. My doctor said, “go easy on my knee.”

Soon after taking these new cholesterol medications, I felt a sharp and sudden pain in my knee as my wife and I were walking to our car. My wife drove us home and she got me to the chair and we elevated my leg and got plenty of ice on it.

We made an appointment at the doctors. Here I was given the reason why my knee hurt. 

• It must be the exercise program. I should go slower or completely rest.

After a week of not exercising at all, my knee pain, now the pain was in both knees, became so much worse, I could not sleep. My wife began looking up things on the internet. She showed me some articles that said it was the statins, the cholesterol medication causing the knee pain. In fact, she showed me, it is a well-known side-effect.

We made an appointment at the doctor’s where I was told to reduce the cholesterol medication and slowly work my way back up to tolerating it if, in fact, that was causing the knee pain. My doctor was skeptical. 

Even after lowering the cholesterol medication dosage I still had the same pain. My doctor told me to stop taking the statins. After a few days, maybe a week or two, my knee pain reduced significantly but they were still painful. I returned to the doctor and told him that I would try to manage my cholesterol without medications and we will see how I do. I am here because I cannot exercise with my knees like this.

Statins create pain

An international team of university researchers and various national councils published these findings in the journal Arthritis Care and Research (3) in August 2019.

These are key learning points:

• The research surrounding the possible relationship between statin use and outcomes in knee osteoarthritis is limited.
• This study examined 1,127 adults for 4 years who took statins.
• What the researchers were looking for was how did statin use influence:
  • Radiographic osteoarthritis, (how did the knee look in MRI and scans over the 4 year period. Did the MRI/scans look worse?)
  • Symptomatic knee osteoarthritis (did the person in the study have new knee pain symptoms and was this matched by eroding conditions in the knee on MRI and scans?)
  • Overall, did the person’s knee pain get worse?

The BIG RESULTS and CONCLUSIONS: Statins were not good pain medications

• No matter what statin was used: Statin use was not associated with a lower risk of worsening pain. In other words, statins were not good pain medications.
• Atorvastatin (Lipitor) use was associated with a reduced risk of developing pain, whilst rosuvastatin (Crestor) leads to a higher risk of developing pain.

From the researchers: “The effect of statins use on knee osteoarthritis outcomes remains unclear, although in our study those using statins for over five years and those using atorvastatin reported a significantly lower risk of developing knee pain.”

Confusing right?

• First, the Atorvastatin (Lipitor) user was associated with a reduced risk of developing pain AS COMPARED to (Crestor) which lead to a higher risk of developing pain. So the Atorvastatin produced less knee pain risk, but still a risk.
• Either way, if you already have knee pain, cholesterol-lowering medicine will not help make it less painful or from it getting worse.

So again, all these research universities and national resources and a long-term study of over 1000 patients came to this conclusion: “The effect of statins use on knee osteoarthritis outcomes remains unclear. ”

The story of cholesterol-lowering medications and joint pain surrounds the impact of these medications on inflammation. Are statins anti-inflammatory or do they create more inflammation?

Study: “The only significant finding indicated that increased duration of statin use was associated with worsening in knee pain and osteoarthritis.”

There is no general consensus that statins help or statins make things worse. I highlighted the study above because these were findings presented in print in August 2019. They are built on other research that took counter viewpoints.

A study from the Netherlands and a team of Dutch university researchers published in the Annals of the Rheumatic Diseases (4) found that Statin use is associated with more than a 50% reduction in the overall progression of osteoarthritis of the knee.

Yet, Virginia Commonwealth University researchers published in the same journal the Annals of the Rheumatic Diseases, these findings:

• Statin use was not associated with improvements in knee pain, function, or structural progression trajectories.
• The only significant finding indicated that increased duration of statin use was associated with worsening in knee pain and osteoarthritis. (5)

The doctors from the Netherlands responded in print a few months later in proper scientific debate. In this response in the Annals of the Rheumatic Diseases, it was suggested that parts of their study should be re-evaluated to find the benefits of statins. They point out

• “Considering the theoretical effects of statins on osteoarthritis (lowering of serum lipid levels lowering local and systemic inflammation, and prevention of atherosclerosis), it is more plausible that statins could be useful in the early stages of osteoarthritis or even before the initiation of the disease process.”(6)

If I control my cholesterol with diet and exercise, instead of medications, my knee pain can be helped without the medication’s side effects.

Here medical and university researchers published their findings in the influential Scientific Reports (7) from the Nature Publish group in London.

• In the present study of nearly 14,000 participants, the research team identified a positive association between hyperlipidemia (high cholesterol) and elevated risks of knee pain and clinical knee osteoarthritis in middle-aged or older adults.
• There is a relationship between triglycerides and knee osteoarthritis.
• Study results indicate that the influence of lipid-lowering drugs on knee pain and clinical knee osteoarthritis is limited.
• These findings have notable implications for public health because the relatively high prevalence of knee osteoarthritis seriously affects the quality of life for older adults, and hyperlipidemia may be prevented through diet and physical exercise.

The researchers then sought to clarify the contradicting research presented in the two studies above.

• The first study above from the Netherlands demonstrated that lipid-lowering drugs were associated with slower knee osteoarthritis progression.
• The second study from Virginia did not find the same results
• In this study from China, the researchers:
  • did not observe an increased risk of knee pain or clinical knee osteoarthritis among the group of participants without high cholesterol but taking lipid-lowering drugs for prevention of other diseases.
  • However, among participants with high cholesterol, risks for knee pain and clinical knee osteoarthritis were higher among those taking lipid-lowering drugs than among those not taking such drugs.
  • Possible explanations for this finding may be that the participants with hyperlipidemia and the use of lipid-lowering drugs had higher serum lipids before pharmacotherapy and a longer course of hyperlipidemia. Our results suggest that hyperlipidemia may be an independent risk factor for knee osteoarthritis and that the effect of lipid-lowering drugs on this association is limited.

They concluded that their results indicate that hyperlipidemia may be an independent risk factor for knee pain and clinical knee osteoarthritis among middle-aged or older adults. These findings have substantial implications for the prevention of knee osteoarthritis through the reduction of blood lipid levels.

Do Statin use in healthy individuals lead to knee replacement?

In an October 2018 study led by the VA North Texas Health Care System, (8) doctors questioned the use of statin prescriptions as preventative medicine in healthy individuals because

• Statins are among the most commonly prescribed medications and their use for primary prevention in many otherwise healthy individuals, including those who are physically active, is increasing.
• There is conflicting evidence regarding the relationship between statin use and musculoskeletal conditions. Given the rising disability associated with musculoskeletal conditions, understanding predisposing factors, including medication-related exposures, deserves further attention.

Medication-related exposures mean that there is a question that the medication is causing joint pain problems.

• Patients enrolled in a regional military healthcare system between 2003 and 2012 were evaluated in this retrospective cohort study.
• A propensity score was generated to match statin-users and nonusers using 115 baseline characteristics. Outcomes included ICD-9 diagnoses codes for Agency for Healthcare Research and Quality disease categories of non-traumatic arthropathies, use-related injury, and undergoing rehabilitation. Primary analysis examined the outcomes in statin-users and nonusers after propensity score matching using conditional logistic regression analysis.

What were the findings of this study? “Statin use was associated with a significantly increased risk of non-traumatic arthropathies (wear and tear related joint replacement) and use-related injury.”

The statins were sending healthy, people who exercise to joint replacement.

Our results provide additional data that can inform patient and clinician conversations about the benefits and risks of statin use.

The subnote, of course, is through diet and exercise. Please see my article on The evidence that your diet is destroying your joints and will send you to a nursing home.

1 Kaleağasıoğlu F, Olcay E, Olgaç V. Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin. Knee Surgery, Sports Traumatology, Arthroscopy. 2017 Jun 1;25(6):1884-91. [Google Scholar]
2 Eliasson P, Svensson RB, Giannopoulos A, Eismark C, Kjær M, Schjerling P, Heinemeier KM. Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern. PloS one. 2017 Mar 6;12(3):e0172797. [Google Scholar]
3 Veronese N, Koyanagi A, Stubbs B, Cooper C, Guglielmi G, Rizzoli R, Schofield P, Punzi L, Al‐Daghri N, Smith L, Maggi S. Statin use and knee osteoarthritis outcomes: A longitudinal cohort study. Arthritis care & research. 2018 Aug 20. [Google Scholar]
4 Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM, Verhaar JA, Van Glabbeek F, Van Meurs JB, Kerkhof HJ, Hofman A, Stricker BC, Bierma-Zeinstra SM. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Annals of the rheumatic diseases. 2011 Oct 1:annrheumdis-2011. [Google Scholar]
5 Riddle DL, Moxley G, Dumenci L. Associations between statin use and changes in pain, function and structural progression: a longitudinal study of persons with knee osteoarthritis. Annals of the rheumatic diseases. 2013 Feb 1;72(2):196-203. [Google Scholar]
6 Clockaerts S, Van Osch GJ, Bierma-Zeinstra SM. Comment on ‘Associations between statin use and changes in pain, function and structural progression: a longitudinal study of persons with knee osteoarthritis’. Annals of the rheumatic diseases. 2013 May 1;72(5):e9-. [Google Scholar]
7 Zhou M, Guo Y, Wang D, Shi D, Li W, Liu Y, Yuan J, He M, Zhang X, Guo H, Wu T. The cross-sectional and longitudinal effect of hyperlipidemia on knee osteoarthritis: Results from the Dongfeng-Tongji cohort in China. Scientific Reports. 2017 Aug 29;7(1):9739.  [Google Scholar]
8 Makris UE, Alvarez CA, Mortensen EM, Mansi IA. Association of statin use with increased risk of musculoskeletal conditions: a retrospective cohort study. Drug safety. 2018 Oct 1;41(10):939-50. [Google Scholar]

2453

Taking Statins for Cholesterol Could Also Improve Your Knee Osteoarthritis (But It’s Complicated) – CreakyJoints

Statin drugs are widely used to help lower cholesterol levels and prevent heart attacks and heart disease, but these drugs can have wide-ranging impacts throughout your body — including your joints.

A growing body of research suggests that statins may affect joint pain for either better or worse, depending on the study you’re reading. Now the results of a new study from Italian researchers, published in the journal Arthritis Care & Research, adds to the debate.

The researchers followed a group of 4,448 people who all had knee osteoarthritis with pain or who were at a high risk of developing knee osteoarthritis, because of their family history or obesity. They researchers surveyed the participants about which statin drugs they were taking. They followed the participants for four years to see how participants’ osteoarthritis was affected.

They found that people who took statins did not report a significant decrease in risk for worsening pain, with one exception: Those people who had been taking statins for longer than five years did report a decrease in pain.

However, the particular kind of statin may matter. While atorvastatin (Lipitor) was linked with a lower risk of worsening pain, rosuvastatin (Crestor) was associated with an increased risk of worsening pain.

Past studies have also reported a link between statins and a decreased risk of osteoarthritis. A Dutch study from 2012 found that people with knee osteoarthritis who took statins had a 50 percent reduction in the progression of their OA compared with people who didn’t take statins. A UK study from 2013 found that people on the highest doses of statins were 60 percent less likely to have osteoarthritis than those who weren’t on them.

How Could Statins Ease Osteoarthritis Pain?

Statins work in the liver to lower cholesterol by blocking a liver enzyme that produces cholesterol. But statins also have strong anti-inflammatory properties. When it comes to osteoarthritis, statins may reduce the level of inflammatory cytokines (proteins released by the immune system) and interfere with the immune system’s T cells — both of which influence osteoarthritis, MedPage Today reports.

It may also be the case that having high levels of fat in the blood, which is what causes high cholesterol, may also contribute to a faster progression of osteoarthritis. So by helping to lower levels of blood fats, statins could benefit your heart and knees at the same time.

According to MedPage, a possible explanation for the lower pain risk among people taking atorvastatin is its lipophilic properties, which can prevent collagen breakdown in the cartilage of the knee.

How Could Statins Worsen Osteoarthritis Pain?

However, statins are also known for causing muscle pain as a potential side effect. Muscle pain doesn’t affect everyone taking statins, but for some people, it can be a challenging side effect and ultimately cause them to discontinue taking the drugs.

Of course, muscle pain and joint pain are separate issues, and more research is needed to understand how and why statins, or certain types of statins, might increase joint pain for some people. Some research has found links between statin use and OA progression. In a 2012 study published in the journal Annals of the Rheumatic Diseases, researchers found that taking statins for longer periods was linked with people reporting worsening physical function scores.

If You’re Taking Statins, Here’s What These Findings Mean for You

It’s premature for doctors to prescribe statins specifically to treat osteoarthritis symptoms or prevent disease progression.

But if you’re taking statins to manage your cholesterol levels, it’s good to be aware that they could have an impact on the health of your knees and other joints.

If you’re concerned about your osteoarthritis risk, ask your doctor about which kind of statins might be best to help improve both your heart and joint health.

Learn More

Statins Side Effects: Pain, Inflammation, and More

What Are Statins?

Statins are a class of drugs often prescribed by doctors to help lower cholesterol levels in the blood. By lowering the levels, they help prevent heart attacks and stroke. Studies show that, in certain people, statins reduce the risk of heart attack, stroke, and even death from heart disease by about 25% to 35%. Studies also show that statins can reduce the chances of recurrent strokes or heart attacks by about 40%.

Who Should Take Statins?

Estimates are that in addition to the people already taking them, another 15 million to 20 million people should be taking statin drugs based on their risk factors for heart disease. Your doctor can do a simple blood test to determine the amount of cholesterol in your blood. If you have high levels of LDL (“bad”) cholesterol, you have a greater chance of heart disease, especially when there are other factors that increase your risk. Based on your overall risk, your doctor may recommend you take statins to help lower your cholesterol by a certain amount.

However, not all cholesterol is bad. It’s good, for instance, to have high levels of HDL (“good”) cholesterol. HDL cholesterol prevents plaque buildup in the arteries by transporting the bad (LDL) cholesterol out of the blood to the liver. From there, it is eliminated from the body.

How Statins Work

Statin drugs work by blocking the action of the liver enzyme that is responsible for producing cholesterol. Too much cholesterol in the blood can cause a buildup of plaque on the walls of the arteries. That buildup can eventually cause the arteries to narrow or harden. Sudden blood clots in these narrowed arteries can cause a heart attack or stroke.

Statins lower LDL cholesterol and total cholesterol levels. At the same time, they lower triglycerides and raise HDL cholesterol levels. Statins may also help to stabilize plaques in the arteries, making heart attacks less likely.

Maintaining a healthy lifestyle while taking a statin can improve the effectiveness of the drug. Be sure to:

Statin Side Effects

Most people who take statin drugs tolerate them very well. But some people have side effects.

The most common statin side effects include:

Less common side effects you may have with statins are:

• Nausea
• Hair loss
• Pins and needles sensations, such as pricking, numbness, or tingling on your skin
• Liver inflammation, which can make you feel like you have the flu
• Pancreas inflammation, which can cause stomach pain
• Skin problems such as rashes or acne
• Sexual problems, such as erectile dyfunction or a low sex drive 

Statins also carry warnings that memory loss, mental confusion, neuropathy, high blood sugar, and type 2 diabetes are possible side effects. It’s important to remember that statins may also interact with other medications you take.

Serious Side Effects of Statins

Statins are linked to a few rare but potentially serious side effects, including:

• Myositis, which is inflammation of the muscles. The risk of muscle injury increases when certain other medications are taken with statins. For example, if you take a combination of a statin and a fibrate — another cholesterol-reducing drug — the risk of muscle damage increases greatly compared to someone who takes a statin alone.
• Elevated levels of CPK, or creatine kinase, a muscle enzyme that when elevated, can cause muscle pain, mild inflammation, and muscle weakness. This condition, though uncommon, can take a long time to resolve.
• Rhabdomyolysis, extreme muscle inflammation and damage. With this condition, muscles all over the body become painful and weak. The severely damaged muscles release proteins into the blood that collect in the kidneys. The kidneys can become damaged trying to eliminate a large amount of muscle breakdown caused by statin use. This can ultimately lead to kidney failure or even death. Fortunately, rhabdomyolysis is extremely rare. It happens in less than one in 10,000 people taking statins.

If you have any unexplained joint or muscle pain, tenderness, or weakness while taking statins, you should call your doctor immediately.

Some studies link statin use with birth defects. Doctors advise pregnant women not to use these drugs.

Statin Side Effects Risk Factors

Some things can increase your risk of side effects with statins. You may be more likely to have side effects if you: 

• Take more than one medication to control your cholesterol
• Are a woman
• Have a small body frame
• Are 80 or older
• Have kidney or liver disease
• Drink a lot of alcohol
• Have some other health conditions, such as hypothyroidism or neuromuscular disorders

Statin Drug and Food Interactions

Some foods and medications don’t mix well with statins and can make side effects worse:

• Grapefruit juice, which has chemical that can change the way your body breaks down statins  
• A drug for irregular heart rhythms called amiodarone (Cordarone, Pacerone)
• Gemfibrozil (Lopid), a cholesterol drug
• Protease inhibitors, a type of HIV medication that includes saquinavir (Invirase) and ritonavir (Norvir)
• Some antibiotic and antifungal drugs, such as clarithromycin and itraconazole
• Certain medications, such as cyclosporine, that lower your immune system activity

There are other medications that can cause problems if you take them with statins. You should tell your doctor about all over-the-counter or prescription drugs, herbal supplements, or vitamins that you use.

Get Relief from Statin Side Effects

Your doctor may be able to suggest some ways to relieve the side effects you have with statins. These changes may help, but talk to your doctor first:

• Take a break from statins, which can help you know if the drugs are the cause of muscle aches or other side effects
• Try a different statin drug or dose
• Change your exercise routine gradually and skip intense workouts if you’re not used to them
• Try another type of medication to lower your cholesterol
• Take coenzyme Q10 supplements, which may stave off side effects in some people  

FDA-approved Statins

The statin medications that are approved for use in the U.S. include:

• Lipitor
• Livalo
• Mevacor or Altocor
• Zocor
• Pravachol
• Lescol
• Crestor

Since their arrival on the market, statins have been among the most prescribed drugs in the U. S., with about 17 million users.

Cholesterol Drugs Linked to Muscle, Joint Problems: Study – WebMD

By Steven Reinberg

HealthDay Reporter

MONDAY, June 3 (HealthDay News) — People taking statin drugs to lower their cholesterol may slightly increase their risk for muscle and joint diseases as well as strains and sprains, a new study suggests.

Statins, such as Zocor and Lipitor, are widely used to reduce cholesterol levels and help prevent heart disease. But they’re also thought to contribute to muscle weakness, muscle cramps and tendon problems.

This new study, based on nearly 14,000 U.S. active-duty soldiers and veterans, confirmed an association between the drugs’ use and musculoskeletal injuries and diseases. But the findings need to be replicated in other types of studies and should not deter people at risk of heart disease from taking the medications, said lead researcher Dr. Ishak Mansi, from the VA North Texas Health Care System in Dallas.

“Do not stop taking statins; these medications have been life-savers for some patients,” Mansi said. “But talk to your doctor about the benefit-risk ratio for you.”

Whether statins should be prescribed universally in people without risk factors for heart disease, as some in the health care field suggest, is another matter, Mansi said.

“The side effects of statins are not totally known yet,” Mansi said. “Advocating widespread use, specifically for primary prevention in otherwise healthy subjects, is unsound.”

The researchers matched nearly 7,000 statin users with a similar number of nonusers to assess the risk of musculoskeletal problems associated with statin use. The results were published online June 3 in the journal JAMA Internal Medicine.

They found that people taking statins had a 19 percent greater risk of having musculoskeletal problems compared with nonusers. Specifically, statin users were 13 percent more likely to suffer dislocations, strains or sprains. They were only 0.7 percent more likely to develop osteoarthritis or other joint problems, which was not considered statistically significant, the researchers found.

The greater likelihood of strains, sprains and dislocations with statin use has not been previously reported, the researchers said. The findings might have implications for physically active people, such as members of the military.

Dr. Gregg Fonarow, spokesman for the American Heart Association, said statin users should be reassured by the findings.

“This study provides further evidence that the proven cardiovascular benefits outweigh any potential risks, including musculoskeletal issues,” said Fonarow, a professor of cardiology at the University of California, Los Angeles.

“Statins have been demonstrated in multiple large-scale, prospective, randomized, placebo-controlled trials to reduce the risk of … cardiovascular events in men and women with or at risk for cardiovascular disease,” he said. “In these gold-standard clinical trials there has been no increased risk of musculoskeletal disease. “

In the current study, three-quarters of the participants were taking simvastatin (brand name Zocor) and about 20 percent were taking atorvastatin (Lipitor). Smaller numbers were prescribed pravastatin (Pravachol), rosuvastatin (Crestor), fluvastatin (Lescol) or lovastatin (Mevacor).

Statins and joint pain

A 42-year-old man presented to his general practitioner (GP) with a history of several weeks of a painful left knee, which had prevented him doing his usual jogging for 20 min several times each week. There was no history of trauma or other precipitant. Past history revealed a 30-year history of insulin-dependent diabetes, for which he took insulin lispro 5 IU t.d.s. and glargine 20 IU nocte. Four weeks earlier, he had increased simvastatin from 10 to 40 mg daily following the finding of changes at retinal screening. There was no history of previous allergy.

Examination revealed a small effusion of the left knee. This was confirmed on X-ray, which showed no other changes. Bloods for arthopathy screen were normal. Simvastatin was stopped for 2 weeks, following which the symptoms completely resolved. He then started pravastatin 20 mg daily and pain returned, although it resolved completely after reducing the dose to 10 mg daily.

Although the Summaries of Product Characteristics and Patient Information Leaflets for simvastatin, atorvastatin, pravastatin and rosuvastatin all list arthralgia as a possible side-effect, the British National Formulary (BNF) is not consistent with this advice since arthralgia is listed as a side effect for atorvastatin and rosuvastatin but not for simvastatin, fluvastatin or pravastatin [1]. BNF does not list arthopathy as a side-effect of any statin. However, the Medicines and Healthcare products Regulatory Agency has reported the following cases of suspected arthralgia/arthopathy as a result of statin use in .

Table 1

UK reports of statins and arthralgia/arthopathy between 1 July 1963 and 18 March 2008

Some statins are more lipophilic (atorvastatin, fluvastatin, simvastatin), whereas others are more hydrophilic (pravastatin, rosuvastatin) [2]. shows that for lipophilic statins there were 294 cases of arthralgia and nine cases of arthropathy, whereas for hydrophilic statins there were cases of 75 arthralgia and one case of arthropathy.

However, although there are relatively high numbers of reports for the more lipophilic simvastatin and atorvastatin, there are very few for fluvastatin. The risk of arthralgia for one of the more hydrophilic compounds, pravastatin, was detected in clinical trials, indicating that the incidence was relatively common; yet in rosuvastatin post marketing studies, arthralgia has only been detected at a very rare reporting rate of <1/10000. In addition, there are clear limitations to the data above since higher counts for simvastatin and atorvastatin are influenced by higher usage in the UK of these two statins. The duration for which each statin has been available also varies. Therefore based on this data there is not enough evidence to support the theory that arthralgia and athropathy occur more with the lipophillic statins.

Since arthralgia and arthopathy are not well-recognized side-effects of statins, such symptoms may not be attributed to such medication. Instead, they may be under-reported and attributed to osteoarthritis, which is common in the predominantly older groups of the population taking statins. GPs should be aware that joint pain in this group may be precipitated and exacerbated by statins, and report such reactions. More evidence is required to show that lipophilic statins may be more likely to produce such effects.

4 Fixes for Achy Muscles Caused by Statins – Cleveland Clinic

Evidence that cholesterol-lowering statins prevent heart attacks and strokes is so compelling that these medications are recommended for people with cardiovascular disease or its risk factors. But statins can sometimes cause side effects that force people to stop taking them and lose the beneficial protection they provide.

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

If this happened to you, there are a few things you can ask your healthcare provider about before giving up on statins.

“True statin intolerance — when a person cannot take a statin even once a week — is extremely rare,” says cardiologist Leslie Cho, MD, Head of Preventive Cardiology and Rehabilitation.

What statin intolerance means

People who are statin intolerant are unable to tolerate the lowest dose of two or more statins, due to the adverse effects that they have on the muscles, joints or liver. Within a month of starting statin therapy, they may feel aches or weakness in the large muscles of their arms, shoulders, thighs or buttocks on both sides of the body.

About 5 to 10% of people who try statins are affected. It’s more common in the elderly, in women and in those taking the more potent statins. Fortunately, these effects disappear within a month after stopping statin therapy.

If you think you can’t take statins, ask your doctor about trying
the following steps.

1. Check for interactions

Sometimes, certain foods or medications prevent the body from
eliminating statins at the normal rate, causing statin levels in the body to
rise. The most common culprits include:

• Heavy alcohol consumption.
• The calcium-channel blockers diltiazem and verapamil.
• The antiarrhythmic drugs amiodarone and digoxin.
• Antibiotics ending in -mycin.
• Antifungal drugs ending in -azole.
• Cholesterol-lowering fenofibrates.

2. Try a different statin

Most statins are lipophilic, which means they passively diffuse into the muscle. These statins, including atorvastatin (Lipitor®), simvastatin (Zocor®) and fluvastatin (Lescol®), are more likely to cause muscle aches. The hydrophilic statins, including rosuvastatin (Crestor®) and pravastatin (Pravachol®), have to be actively transported and cause fewer muscle aches. If you haven’t tried a hydrophilic statin, talk to your doctor about switching to one.

3. Take a lower dose

A little statin is better than none, so try taking the lowest dose
of a hydrophilic statin once a week. For example, start with rosuvastatin 2.5
mg on Mondays. If you can tolerate it, add 2.5 mg on Thursdays. If that doesn’t
bother you, add a third day. Another option is to stay on the twice-weekly
schedule and raise the dose to 5 mg.

“By introducing statins slowly, 70% of “statin intolerant” patients end up being able to take a statin: 60% of them can take it every day, and 10% can take it three times a week,” Dr. Cho says.

4. Try a different option

If you’re still unable to tolerate any statins at all, ask about switching to exetimibe (Zetia®), which can lower LDL by 15%, or a PCSK9 inhibitor. There are two: alirocumab (Praluent®) and evolocumab (Repatha®). These powerful drugs can lower LDL to rock-bottom levels without triggering muscle pain.

The only disadvantage is price. PCSK9
inhibitors are expensive, and some patients have difficulty getting their
prescription approved. That’s why statins remain the more common choice for
lowering LDL cholesterol

A word of warning: Never stop taking a statin without your doctor’s guidance. “It can greatly increase your chance of having a heart attack,” Dr. Cho says.

This article was originally published in Cleveland Clinic Heart Advisor.

Managing Muscle Pain Related to Cholesterol Medication

By Lori C. Dupree, Pharm.D., BCPS

The treatment of high cholesterol has improved care for many people. Most people who have diabetes or those who have had a stroke or heart attack benefit from lower cholesterol levels. Medications called “statins” are the most commonly prescribed drugs used to reduce cholesterol. Some examples of statin medications are Lipitor® (atorvastatin), Pravachol® (pravastatin), Zocor® (simvastatin), Livalo® (pitavastatin) and Crestor® (rosuvastatin).

Unfortunately, some people may experience muscle pain or weakness while taking statins. The pain may be minor such as soreness or stiffness. However, muscle pain, particularly if severe and accompanied by dark-colored urine, may be an indication of a more serious, life-threatening problem called rhabdomyolysis.
Older age and a low body weight are risk factors for developing statin-induced muscle pain. Both the medication dose and the fact that it might be interacting with other medicines a person takes can cause the side effect of muscle pain.

People who take statins and drink large quantities of grapefruit juice may be at increased risk for muscular side effects. People with liver and thyroid problems may also develop muscle pain while taking statins. Finally, new research indicates that genetics may play a role in determining who may develop muscle pain with statins.

Often people may experience muscle pain or discomfort when starting a statin, but usually these symptoms improve after the first few weeks on the medicine. But it’s important to remember that muscle pain may develop even if you have been taking a statin for years.

If you experience muscle pain while taking a statin, contact your health care provider. He or she will likely do a physical exam and check your bloodwork. Both of these tests are important to determine if the statin medication is causing the problem.

If your doctor feels that the statin is contributing to the problem, you probably will be asked to stop the medication to see if your symptoms improve. Sometimes during this “statin holiday,” your doctor may ask you to take coenzyme Q10, l-carnitine or fish oil. However, current research does not clearly show that these supplements are helpful for treating statin-induced muscle pain.

If your muscle pain improves, you and your health care team can decide whether it is acceptable for you to remain off of a statin, or whether you need to continue this type of medication. Sometimes your doctor will prescribe a different kind of medication to treat high cholesterol instead of a statin. However, when the decision is made to continue taking a statin, trying a different statin may work. It is also important to make sure that you are not taking medications that interact with the statin as this can increase the risk of the muscle pain side effect.

Statin medications have made it possible for many people to live longer and healthier lives, but it is important to pay attention to any muscle discomfort you experience while taking these drugs. Even if muscle stiffness, weakness and pain are minor while you are taking a statin, it is important that you discuss these symptoms with your doctor and your pharmacist. That’s because these symptoms may be related to your medication and may indicate more serious complications.

90,000 What they are treating us with: Atoris. Live in pain or die young?

However, according to a comparative analysis of 135 studies, statins do increase the risk of diabetes, cause muscle pain and can be harmful to the liver, but these risks are still quite low. And here atorvastatin was on a par with other statins, and the least side effects were caused by pravastatin and simvastatin. Although statin-related muscle pain appears to be underestimated in clinical trials, severe muscle damage occurs in 1 to 2 people per 10,000 people * years of drug use, concludes a systematic review in The Canadian Journal of Cardiology.

Less serious consequences, which the instruction also warns about (nausea, digestive problems, loose stools, pain in muscles and joints) are much more common – in 1-10% of patients. Also, the US Food and Drug Administration (FDA) in 2014 reported forgetfulness and absent-mindedness when taking statins, but these problems stopped after patients refused the medication.

In terms of recommendations for HIV-positive patients and people taking hemofibrozil, atorvastatin may be the least dangerous option than other statins, as patients in these groups are at increased risk of side effects.

Indicator.Ru recommends: use with an increased risk of heart attack and stroke

Atoris really slows down the development of atherosclerosis and other cardiovascular diseases that increase the likelihood of heart attack and stroke. Its active ingredient is a fairly strong statin and is effective in different dosages: when taken 10 mg per day, it lowers blood cholesterol by 27%, and 80 mg per day by 37.9%, according to another Cochrane review.

And although the side effects of statins are unpleasant, and you cannot expect a dramatic improvement and complete cure from them, you should not stop drinking them without a doctor’s permission.But in reality, the choice is not so hard: according to statistics, health-threatening events (for example, the development of diabetes, serious damage to the liver or muscles) are considered very rare, and more frequent symptoms, such as muscle pain or nausea, are not dangerous. Despite this, while some patients use statins for prophylaxis, being healthy (this is especially common in the USA and Europe), others drop out of therapy that could prolong their life for years.

Here, the truth lies somewhere in between: the benefits of the drug for healthy people are questionable, although statins are unlikely to cause significant harm.However, there is hope for prevention: A 2013 Cochrane Review shows that statins help prevent cardiovascular complications in an average of 18 out of 1000 patients who initially had hypertension, diabetes, or high cholesterol. Therefore, in the case of statins, everything depends on the patient’s condition.

Of course, do not forget about a healthy lifestyle: sometimes it is enough to stop eating fatty foods in order to lower blood cholesterol levels to normal values ​​without the help of medications.And even with medications, eating a healthy diet won’t hurt you either.

Our advice cannot be equated with a doctor’s prescription. Before you start taking this or that drug, be sure to consult with a specialist.

Like the stuff? Add Indicator.Ru to Yandex.News “My sources” and read us more often.

Subscribe to Indicator.Ru in social networks: Facebook, VKontakte, Twitter, Telegram, Odnoklassniki.

Statins and muscle pain

We have already written about the dangers of statins for, fortunately, small groups of patients who develop side effects of their use.The most common adverse effects of statins are muscle pain. What to do in such cases? Does such a patient automatically have to lose the protection against the progression of atherosclerosis that statins give?

In clinical practice. If the patient is taking statins and complains of muscle pain, the following should be done.

1. Assess whether pain is really a side effect of statins,
2. To evaluate modifiable risk factors for statin-associated muscle syndrome
3. Assess the benefit / risk ratio of statin use in a given patient,
4. Assess whether the selection of a statin and its dose is optimal. the possibilities of combination therapy and alternative treatment strategies.

Is muscle pain associated with a statin?

If muscle pain and fatigue are symmetrical, appear in large muscles, occur about two weeks after starting a statin and have passed two weeks after stopping it, then the likelihood that they are caused by a statin is very high.

In contrast, if pain is localized and appeared more than a month after starting treatment and does not disappear after stopping the statin, the likelihood that it is associated with taking a statin is very low.

To determine the relationship of muscle pain with statin intake, you can use a scale in points:

The range of conditions in which muscle pain can occur is quite wide. All of them must be excluded before deciding whether to continue statin therapy:

Muscle pain should be distinguished from joint pain:

Factors contributing to muscle pain when taking statins

Such factors can be modifiable (which can be influenced) and unmodified (which cannot be influenced). An example of a combination of non-modifiable and modifiable factors is the occurrence of muscle pain in women with low body weight. It is impossible to change the gender, but the lack of body weight can be made up.

Important modifiable factors are drug interactions (effects that occur when taking several drugs) and drug interactions with food, for example, with grapefruit juice. In this regard, before taking the drug, it is necessary to study the documentation attached to it and determine whether among the drugs already taken there are those that will adversely interact with the prescribed statin.Interaction with grapefruit juice is observed quite often and depends on the amount and quality of the juice consumed, as well as the dose and time of taking the statin. If the patient drinks the juice 12 hours or more before taking the statin, the chance of interaction is minimal. Most often, this interaction is observed with simvastatin and sometimes with atorvastatin.

A significant vitamin D deficiency is an important risk factor. It is known that severe untreated vitamin D deficiency can lead to muscle pain.A recent study showed that when patients receive a vitamin D supplement and the deficiency is corrected, 80% of them are able to take statins again without side effects.

Statin treatment strategy for muscle pain

It is possible to eliminate the side effect by choosing the drug, since the metabolism is significantly different (for the differences between statins, see our article “Use of statins: considering the differences between drugs”). You should try at least three different drugs.

Muscle side effects are significantly dependent on the dose of statin taken. It is possible to reduce the doses of statin, followed by the selection of a combined treatment with the inclusion of ezetimibe and resins in the treatment regimen.

Another option to manage side effects without stopping treatment is to use alternative statin dosing regimens.Read about this in our article “Statins: Alternative Dosing Regimens”.

Data are now available on the treatment of muscle damage with statin use. Such treatment helps to continue taking statins and relieve the manifestations of their effects on the muscles. For this it is recommended to use:

• Coenzyme Q
• Vitamins D or E

Based on the materials of the special session of the Congress of the European Society of Cardiology, 2015.

Our comment

In particular, all of the above applies to patients who are undergoing secondary prevention of cardiovascular events. Continuing statin therapy for them is a major factor in preventing new episodes of illness and keeping them alive. Therefore, you should not recklessly refuse to take a statin.

Nothing is easier than stopping treatment. Reasonably weighing the risks and benefits of such treatment, and on this basis, making a final decision is more difficult, but necessary.

Discuss material or ask questions on Facebook.

90,000 Why statins hurt muscles

When statins are treated, there is too much anti-inflammatory protein in muscle cells, which causes the cells to simply die.

Statins are a group of drugs that lower blood cholesterol levels. Statins are highly effective, are most often prescribed for atherosclerosis, and are generally considered to be easily tolerated in the sense that the benefits outweigh the side effects. However, statins have side effects, and one of the most common is muscle pain. Muscle problems occur in 5–29% of patients taking statins, most often the elderly and women, as well as those who lead a physically active lifestyle.

Researchers from the University of Saar have tried to understand the causes of “statin pain” in muscles. In an article in The FASEB Journal , they write that it is all about the GILZ protein. It is synthesized in a wide variety of tissues and organs, including muscles. GILZ is needed to keep the immune system in check: it appears in response to stress hormones glucocorticoids and inflammatory immune signals, suppressing inflammation and calming the immune system. Statins, in turn, not only lower cholesterol – they also suppress inflammation, and they do so with the help of the GILZ.

Under the action of statins, cells synthesize more anti-inflammatory protein GILZ, but with an increase in GILZ in muscle cells, they begin to die (therefore, obviously, in the most severe cases, everything ends with rhabdomyolysis, when muscle tissue is visibly degraded). If the gene encoding GILZ was turned off in the cells, then there was no harm to the cells from statins. And since now we more or less know exactly how statins harm muscles, then, perhaps, soon the treatment with statins will be able to be modified so that they do not interfere with the work of the anti-inflammatory protein GILZ and do not force cells to die.

Amlodipine and Atorvastatin | Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ^® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA

Caduet

Trade names: Canada

APO-Amlodipine-Atorvastatin; Caduet; GD-Amlodipine / Atorvastatin; PMS-Amlodipine-Atorvastatin

What is this drug used for?

• Used to treat high blood pressure.
• Used to lower bad cholesterol and raise good cholesterol (HDL).
• Used to lower triglyceride levels.
• Used to treat certain types of chest pain (angina).
• Used to reduce the risk of myocardial infarction, stroke and death in some people.
• This medicinal product can be used for other indications. Consult your doctor.

What do I need to tell my doctor BEFORE taking this drug?

• If you are allergic to this drug, any of its ingredients, other drugs, foods or substances.Tell your doctor about your allergy and how it manifested itself.
• In one of the following: current liver disease or elevated levels of liver enzymes in the blood.
• If you are taking any of the following drugs: cyclosporine, gemfibrozil, glecaprevir in combination with pibrentasvir, letermovir, or tipranavir in combination with ritonavir.
• If you are taking any of the following medicines: cimetidine, ketoconazole, or spironolactone.
• If you are or may become pregnant. Do not take this drug if you are pregnant.
• If you are breastfeeding. Do not breast-feed while taking this drug.

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems.You need to make sure that this drug is safe for your medical conditions and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

• Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
• Avoid driving or other activities that require increased attention until you see how this drug affects you.
• To reduce the risk of dizziness or loss of consciousness, get up slowly from a lying or sitting position. Use caution when climbing and descending stairs.
• Perform blood tests as directed by your doctor. Please consult your doctor.
• Check blood pressure as directed.
• If you have high blood sugar (diabetes), your blood sugar should be checked regularly.
• Talk to your doctor before taking an over-the-counter drug that can increase blood pressure. These drugs include medicines for coughs and colds, diet pills, stimulants, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen, and some naturally occurring drugs.
• Avoid or limit alcohol to less than 3 servings per day. Drinking too much alcohol can increase your risk of liver disease.
• Consult a healthcare professional if you frequently drink grapefruit juice or eat grapefruit.
• Follow your doctor’s recommended diet and exercise program.
• If you take this drug for chest pain, it will not heal the chest pain when it occurs. This drug is used to prevent or reduce attacks of chest pain.
• In rare cases, chest pain may develop or worsen for the first time after the first dose of this drug or after an increase in dose. Myocardial infarction can also occur. The risk may be increased in people with very severe heart blood vessel disease. Consult your doctor.
• If you are 65 years of age or older, use this drug with caution. You may have more side effects.
• Potential adverse effects of this drug on the fetus.If you can become pregnant, you must use contraception during treatment. If you become pregnant, contact your doctor immediately.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor or get medical help right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

• Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
• Signs of a urinary tract infection, including blood in the urine, burning or painful sensations when urinating, frequent or immediate urge to urinate, fever, pain in the lower abdomen or pelvis.
• Weakness on one side of the body, difficulty speaking or thinking, trouble maintaining balance, drooping one side of the face, or blurred vision.
• Severe dizziness or fainting.
• Shortness of breath, sudden weight gain, or swelling of the arms or legs.
• When chest pain occurs or worsens.
• Muscle stiffness, tremors or abnormal muscle movements.
• This drug may cause muscle pain, soreness, or weakness. The risk may be increased with thyroid dysfunction or kidney problems. It may also be raised if this drug is taken with certain other drugs or for people 65 years of age or older. Occasionally, severe muscle abnormalities can occur, which can lead to impaired renal function.Fatalities occurred on rare occasions. If you experience muscle pain, tenderness, or weakness (with or without fever, or feeling unwell), seek medical attention immediately. Call your doctor right away if muscle problems persist after you stop taking this drug as directed by your doctor.
• Liver problems have rarely happened with this drug. Sometimes these cases were fatal. Call your doctor right away if you have signs of liver problems such as dark urine, tiredness, lack of appetite, nausea or abdominal pain, discolored stools, vomiting, yellowing of the skin or eyes.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

• Joint pain.
• Diarrhea.
• Nausea.
• Feeling dizzy, tired, or weak.
• Nose or throat irritation.
• Sleep disorders.
• Pain in the arms or legs.

This list of potential side effects is not exhaustive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088.You can also report side effects at https://www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

• Take this medication with or without food.
• This medication must not be broken up. If you are unable to swallow the pill, tell your doctor.
• If you have difficulty swallowing, consult your doctor.
• Take this drug at about the same time of the day.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.

What to do if a dose of a drug is missed?

• Take the missed dose as soon as you can.
• If there is less than 12 hours before your next dose, skip the missed dose and go back to your normal schedule.
• Do not take 2 doses at the same time or an additional dose.

How do I store and / or discard this drug?

• Store at room temperature in a dry place. Do not store in the bathroom.
• Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
• Dispose of unused or expired drugs.Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. Your area may have drug recycling programs.

General information about medicines

• If your health does not improve or even worsens, see your doctor.
• You should not give your medicine to anyone and take other people’s medicines.
• Some medicines may have other patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• Some medicines may have other patient information sheets. Check with your pharmacist. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Consumer use of information and limitation of liability

This information should not be used to make decisions about taking this or any other drug. Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are suitable for a particular patient.This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug. This information should not be construed as a treatment guide and does not replace information provided to you by your healthcare professional.Check with your doctor for complete information on the possible risks and benefits of taking this drug. Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc. and its affiliates and / or licensors, 2021. All rights reserved.

90,000 Statin use can damage the musculoskeletal system

Statin use is associated with an increased risk of musculoskeletal and joint disease according to a new retrospective analysis published June 3 in the American Medical Association’s Journal of Internal Medicine.

Researchers retrospectively compared the likelihood of developing musculoskeletal disorders among 6967 patients on statins versus 6967 patients not on statins using a similar likelihood selection. The majority of patients took simvastatin (73.5%), about one third of patients took the maximum dose of drugs, simvastatin 80 mg, atorvastatin 80 mg or rosuvastatin (Crestora, AstraZeneca) 40 mg. The use of simvastatin 80 mg is currently limited in the US market due to possible muscle damage.Diseases of the musculoskeletal system were defined in accordance with the International Classification of Diseases, Ninth Revision (ICD-9). The results showed that statin treatment was associated with a 19% increased risk of any type of musculoskeletal injury (p

“To our knowledge, this is the first study using similar likelihood selection to show that statin use is associated with an increased likelihood of illness and injury to the musculoskeletal system,” the researchers report.These results are very important because the initiation of statin therapy at a young age for the primary prevention of cardiovascular diseases is now widely promoted.

The researchers note that there are limitations in ICD-9 for defining musculoskeletal disorders, although selection for similar in likelihood eliminated differences in baseline characteristics between the two cohorts, underlying confounding factors may have persisted.Therefore, further large studies are required to obtain more accurate information regarding the risks and benefits of statin therapy.

“The benefits of statins in reducing cardiovascular events continue to offset their negative effects on the musculoskeletal system,” the scientists report.

Source: www.cardiosource.org

www.theheart.org

Ingavirin: drug review

Ingavirin medicine

Ingavirin is a drug, the action of which is aimed at the treatment and prevention of acute respiratory viral infections, as well as influenza.

When taking the drug, interferon is actively produced, which activates human immunity against the virus. The resulting cytotoxic lymphocytes, together with NK cells, actively suppress the action of pathogenic microorganisms, killing them and preventing them from spreading throughout the body. This prevents the progression of the disease or its onset.

In the treatment of sore throats, flu and other diseases, Ingavirin helps to calm the fever, and also reduces the intoxication of the body and relieves catarrhal manifestations.In addition, the drug prevents complications and shortens the overall course of the disease.

Ingavirin Composition

The main active ingredient in Ingavirin is pentanedioic acid imidazolylethanamide. In addition to it, the preparation contains excipients that enhance the effect of the preparation. Ingavirin was included in the state register of medicines of the Russian Federation in 2008.

Release form and dosage

Ingavirin is produced for both children and adults

Children’s Ingavirin is produced in capsules of 60 mg.

Adult Ingavirin is also available in capsules, 90 mg each.

Readings

Ingavirin can only be consumed after consulting a doctor. The drug is prescribed for adults and children from 3 years old for the treatment and prevention of influenza A and B, as well as respiratory and viral infections.

Schemes for taking Ingavirin

The drug is taken orally at any time. Before, after or during a meal – it makes no difference.

Children from 3 to 6 years old may have some difficulties with taking the drug.To alleviate the situation, you can simply dissolve the contents of the capsule. It is usually dissolved in water or apple juice at room temperature. You can also add some sugar to mask the taste of the medicine. It is important to mix the preparation thoroughly and drink immediately. You cannot store the prepared mixture. Prescribe no more than 30 mg. the drug once a day. Children from 7 years old Ingavirin are prescribed 60 mg, and adults take the drug 90 mg once a day.

The period of treatment with Ingavirin for children from 3 years old usually lasts no more than 5 days.Children over 7 years old, as well as adults, take the drug a little longer – about 7 days. It is recommended to take Ingavirin as soon as the first ailments begin to appear. Treatment will be more effective if you start taking Ingavirin immediately.

If a patient has previously been diagnosed with diseases of the cardiovascular and respiratory system, diabetes and obesity, in the first days of taking the drug, the dose is doubled. After three days, the dosage is reduced to standard.If, after the course of treatment, no improvement is observed, or, on the contrary, the patient’s condition worsens and new symptoms appear, the drug is stopped before consulting with the attending physician. At the same time, it is important to strictly observe the dosage and recommendations of the doctor and the instructions for the drug.

As a prophylactic agent, Ingavirin is prescribed during periods of exacerbation of the epidemiological situation, as well as after contact with people with viral diseases. The prophylactic course also lasts 5 days for children under 7 years of age and 7 days for older patients.

Contraindications

Ingavirin is not prescribed either as a prophylactic or as a treatment for children under 3 years of age. In addition, it is forbidden to use the drug if the following factors are present:

• high sensitivity to any component of the drug;

• lactose intolerance;

• pregnancy and lactation;

• lactase deficiency;

• malabsorption of the glucose-galactose type.

Special Recommendations

Ingavirin is not recommended to be taken simultaneously with other drugs of similar action. Especially without first consulting a doctor. For any questions about taking the drug, you must definitely contact your doctor. It is also recommended not to throw away the instructions. In addition, it is not recommended to use the drug in conjunction with antibiotics. Antibiotics can completely stop the action of Ingavirin as they actively suppress the action of any microorganisms.

Ingavirin for children

Ingavirin is sold in pharmacies in a special dosage for children. Like adults, children are prescribed a drug for prevention and treatment. The course of treatment and dosage of the drug are indicated in the instructions and are adjusted by the attending physician throughout the entire period of taking the drug. It is fashionable to take children’s Ingavirin only from the age of three.

Ingavirin for pregnant and lactating

Throughout the entire period of pregnancy and during breastfeeding, it is not recommended to take the drug, since the effect of Ingavirin is not fully understood.If there is a need to prescribe a remedy, you should refrain from breastfeeding throughout the entire period of treatment.

Ingavirin and alcohol

The action of Ingavirin is aimed, first of all, at activating healthy cells of the body in the fight against the virus. Alcohol, on the contrary, reduces the body’s ability to resist not only viruses, but also other types of diseases. That is why it is better to suppress the joint intake of the drug and the use of alcohol in any dose.

In addition, alcohol can not only reduce the therapeutic effect of the drug, but also aggravate the course of the disease. Special studies were carried out for the joint intake of Ingavirin with alcohol. As a result of the study, it was possible to identify the following:

• The drug helps to reduce nasal discharge, relieves cough, relieves sore throat. Alcohol, on the other hand, exacerbates these symptoms.

• Ingavirin is able to completely eliminate headache.Alcohol is known to be one of the main migraine provocateurs. Moreover, even if there was no headache before taking the drug, alcohol in most cases causes it.

• Decrease in temperature and elimination of fever and chills due to the intake of Ingavirin occurs within a day. Alcohol, on the other hand, increases this effect of the drug by at least three days.

• The drug strengthens the immune system.Alcohol, on the other hand, has no benefit for the immune system.

Taking Ingavirin in order to prevent and protect against recurrence of colds and flu allows the substances of the drug to act in the body for a whole month. Drinking alcohol during the prophylaxis period reduces the effect of the drug to 10 days.

Ingavirin and digestion

Ingavirin’s effects on digestion have not been proven. In people who do not have problems with the gastrointestinal tract, as well as lactose intolerance, side effects from the gastrointestinal tract have not been identified.In addition, the components of the drug are easily absorbed by the body. The drug is excreted naturally. From the gastrointestinal tract, the components of the drug are quickly transferred into the blood and other organs. The maximum concentration of the drug is reached within 30 minutes. Ingavirin is not metabolized in the body. Within a day, most of it is excreted from the body.

Rosuvastatin – Evidence-Based Medicine for All

Rosuvastatin

Item

Crestor, Mertenil

Pharmacological action

Rosuvastatin – lipid-lowering agent, statin.The active ingredient of the drug is rosuvastatin, a competitive selective inhibitor of HMG-CoA reductase, an enzyme that transforms 3-hydroxy 3-methylglutaryl coenzyme A into a cholesterol precursor, mevalonate. The site of application of the action of rosuvastatin is the liver, where catabolism of low density lipoproteins (LDL) and the formation of cholesterol (CS) occurs. Rosuvastatin increases the number of hepatic low-density lipoprotein receptors on cell membranes, which leads to increased catabolism and uptake of low-density lipoproteins and suppression of the formation of very low-density lipoproteins (VLDL).As a result, there is a decrease in the content of low and very low density lipoproteins in the blood serum.
Rosuvastatin reduces elevated levels of total cholesterol, triglycerides and LDL cholesterol, apolipoprotein B (ApoV), VLDL cholesterol, non-HDL cholesterol, VLDL TG, the ratio of LDL cholesterol / HDL cholesterol, total cholesterol / HDL cholesterol / LDL / Apo / C non -I. Rosuvastatin slightly increases the content of HDL cholesterol and ApoA-I (apolipoprotein A-I).
The maximum effect of rosuvostatin develops after 21 days of administration and remains constant.After 7 days of taking the drug, the therapeutic effect of rosuvostatin is observed, and after 14 days of taking the drug, the effectiveness of the drug is 90% of the maximum possible.
The drug is indicated for adults with or without hypertriglyceridemia and hypercholesterolemia, regardless of age, gender or race. The drug can also be used in patients with familial hypercholesterolemia or diabetes mellitus.
While taking rosuvastatin at a dosage of 10 mg in 80% of patients with an average baseline LDL cholesterol level of 4.8 mmol / L (hypercholesterolemia IIa and in types), a decrease in LDL cholesterol to ≤3 mmol / L is observed.In patients with familial hypercholesterolemia, who receive the drug at a dosage of 20–80 mg, a positive change in the lipid profile is observed (a clinical study was conducted with the participation of 435 patients).
A 53% decrease in LDL cholesterol was observed with 12 weeks of rosuvastatin therapy after titration of a dose of 40 mg / day, and an LDL cholesterol level of ≤3 mmol / l was achieved in 33% of patients. Patients with familial homozygous hypercholesterolemia were prescribed the drug at a dosage of 20 and 40 mg, and against the background of treatment with rosuvastatin, the decrease in LDL cholesterol was 22%.
When combined with fenofibrate, an additive effect (triglyceride level) was recorded, which was also observed when combined with nicotinic acid (in relation to HDL cholesterol).
Data are not yet available to assess the reduction in complications associated with lipid abnormalities (eg, coronary artery disease) – clinical trials are ongoing.
The maximum concentration of the active substance in the blood plasma is observed approximately 5 hours after the internal use of Crestor.Bioavailability is approximately 20%. Cumulates in the liver. The volume of distribution of rosuvastatin is 134 liters. Approximately 90% of the administered dose is bound by plasma proteins (albumin).
Approximately 10% of a dose of rosuvastatin undergoes limited metabolism. Rosuvastatin is a non-core substance for metabolism carried out by the cytochrome P450 system. The main enzyme that metabolizes rosuvastatin is CYP 2C9. To a lesser extent, the enzymes CYP 3A4, CYP 2C19 and CYP 2D6 are involved in the metabolism of rosuvastatin.The main metabolites of the active substance are lactone metabolites and N-dismethyl. When comparing them, it turned out that N-dismethyl is about half (50%) less active than rosuvastatin. It has been determined that lactone metabolites are pharmacologically inactive.
The mean geometric clearance of rosuvastatin is about 50 l / h with a coefficient of variation of 21.7%. Approximately 90% of the administered dose is eliminated unchanged in the intestine with feces, and both unabsorbed and absorbed rosuvastatin are excreted.10% of the substance is eliminated by the kidneys. The half-life is approximately 19 hours, which is unchanged with increasing dosage. In the process of hepatic uptake of the active molecule of the substance (as with other inhibitors of HMG-CoA reductase), a cholesterol transporter is involved, which plays an important role in the elimination of rosuvastatin by the liver.
The systemic exposure of rosuvastatin increases in proportion to the dose administered. In the case of taking several daily doses of the drug, the pharmacokinetic parameters of the active substance of rosuvastatin do not change.
A comparative study in patients living in Asia (Asian race) revealed an increase in AUC and a 2-fold increase in the maximum concentration of rosuvastatin, compared with the data in Europeans living in Europe and Asia. The influence of environmental and genetic factors on the obtained difference in pharmacokinetic parameters was not revealed. There were no clinically significant differences in the pharmacokinetics of rosuvastatin between patients of the Negroid and Caucasian races.
In case of impaired renal functions (mild or moderate), the plasma content of rosuvastatin and its active metabolite (N-dismethyl) does not change significantly.In severe renal failure with a creatinine clearance level of ≤30 ml / min, the plasma concentration of the active substance increases 3 times (and the active metabolite, N-dysmethyl, increases 9 times). The plasma concentration of rosuvastatin in patients receiving chronic hemodialysis is approximately 50% higher. A study to study the pharmacokinetic parameters of rosuvastatin in patients with kidney disease was carried out in comparison with a group of healthy volunteers.
There was no increase in the parameters of the half-life of the active substance in patients with different degrees of hepatic insufficiency, which were assessed on the Child-Pugh scale of 7 or less points.In patients rated at 8 and 9 points on the Child-Pugh scale, an increase in the half-life of at least 2 times was observed. There is still no experience with the use of rosuvastatin in patients with hepatic insufficiency with a Child-Pugh score of 9 or more.

Indications for use

Therapy of atherosclerosis to slow the progression of the disease in patients who are indicated for lipid-lowering treatment;
for homozygous familial hypercholesterolemia as an adjunct to other cholesterol-lowering treatment (eg, LDL apheresis) or diet, as well as in cases where such treatment is ineffective;
as an addition to the diet – with mixed hypercholesterolemia (type IIc) in the case when non-drug methods (weight loss, physical activity) and dietary changes are ineffective;
primary hypercholesterolemia type IIa (including familial heterozygous hypercholesterolemia).

Method of application

The drug is taken orally with water, at any time of the day, regardless of food intake. Do not chew.
The dose of rosuvastatin is selected depending on the response to treatment and the purpose of using rosuvstatin, while recommendations for target lipoprotein levels should be taken into account. During treatment with the drug, the patient is prescribed a lipid-lowering diet (standard) for constant use.
In case of replacing the use of other HMG-CoA reductases or with the first appointment of Crestor, a starting dosage of 5-10 mg / day is recommended.The choice of dose depends on the individual parameters of cholesterol, the risk of side effects and risk factors for future complications from the cardiovascular system. If the effect is insufficient, the dosage of Crestor can be increased no earlier than 21 days after the start of taking the drug (since the maximum therapeutic effect develops precisely by this time). Taking Crestor at a dose of 40 mg causes an increased risk of side effects of the drug compared to lower dosages, therefore, an increase in the dose of rosuvastatin to 40 mg / day is allowed only with a high degree of risk of developing cardiovascular complications (including patients with familial hypercholesterolemia) and with severe hypercholesterolemia.An increase in dosage to 40 mg / day is carried out only if the desired effect from the use of rosuvastatin at 20 mg / day has not been achieved, while the patient should be under close medical supervision. Particular attention to such a patient is necessary during the first days of taking Crestor at a dose of 40 mg / day.
Increasing the dose is advisable in the event that the desired result is insufficient when taking a dosage of 20 mg and provided that the patients are under the close supervision of a specialist.Special control is recommended at the beginning of taking 40 mg of the drug.
Patients with a geriatric profile do not need to adjust the dosage of the drug.
In renal failure
In patients with mild degree, dose adjustment is not required. For patients with moderate renal failure, the starting dose of rosuvastatin should be 5 mg / day.
The maximum daily dosage for mild renal failure is 40 mg / day, for moderate renal failure (with a creatinine clearance level of ≤60 ml / min) – 20 mg / day.
Rosuvastatin is contraindicated in patients with severe renal impairment.
In liver failure
There is no experience of using rosuvastatin in patients with liver failure who have been assessed on the Childe-Pugh scale of 9 points or more. The appointment of rosuvastatin to patients with liver disease in the active phase is contraindicated.
Ethnic groups
There is an increase in the systemic concentration of rosuvastatin in patients of the Mongoloid race.Such patients should start therapy with a dosage of 5 mg / day, with a maximum dose of 20 mg / day. The appointment of rosuvastatin for patients of the Mongoloid race at a dosage of 40 mg / day is contraindicated.
With a tendency to develop myopathy
In patients with a tendency to develop myopathy, the starting dose of rosuvastatin should be 5 mg / day, the maximum dose should be 20 mg / day. Such patients are contraindicated in the appointment of a dose of rosuvastatin 40 mg / day.

Side effects

The incidence of side effects, as with other HMG-CoA reductase inhibitors, depends on the dose used.
The incidence of side effects was assessed as follows: frequent side effects (≥1 / 100, ≤1 / 10), infrequent side effects (≥1 / 1000, ≤1 / 100), rare side effects (≥1 / 10,000, ≤ 1/1000), very rare side effects (≤1 / 10,000). Side effects when using Crestor were assessed as moderately pronounced and self-limited.Discontinuation of Crestor therapy during clinical trials due to the occurrence of side effects was 4% or less.
From the nervous system: dizziness, headache (often).
From the immune system: allergic reactions (including angioedema) are rare.
On the part of the skin and its appendages: rashes, itching, urticaria (infrequent side effects).
From the musculoskeletal system: rhabdomyolysis and myopathy (rare), muscle pain (often).Myopathy, muscle pain, and (rarely) rhabdomyolysis have been reported in patients who took any dose of rosuvastatin, but especially in those who used a dosage of 20 mg / day. The dose-dependent increase in the level of creatine phosphokinase (CPK), observed in patients who took rosuvastatin, in most cases was not expressed, transient and without symptoms. In the case of an increase in the level of CPK 5 or more times, the reception of rosuvastatin is stopped.
From the gastrointestinal tract: constipation, abdominal pain, nausea (common), pancreatitis (rare).
From the urinary system: tubular proteinuria. There was a change in the amount of protein in the urine in a gradation from no protein to traces of protein or up to two pluses or more in ≤1% of patients who were prescribed a dose of rosuvostatin 10–20 mg / day. At a dose of 40 mg / day, the number of such patients was approximately 3% of patients. When using a dosage of rosuvastatin of 20 mg / day, slight increases in the amount of protein in the urine were observed. Proteinuria in most cases decreased or disappeared with continued administration and was not a symptom of the development of acute kidney disease or the progression of an existing one.
On the part of the liver: a small number of patients showed a dose-dependent increase in the content of transaminases, as with the use of other inhibitors of HMG-CoA reductase. The increase in transaminases in most cases was transient, without symptoms and insignificant.
Others: Asthenia (common).
After the widespread introduction of rosuvostatin into medical practice, the following side effects have also been reported:
From the musculoskeletal system: joint pain (rare).
From the nervous system: polyneuropathy (very rare).
From the hepatobiliary system: hepatitis and jaundice (very rare).

Contraindications

Liver diseases in the active stage, including a persistent increase in the level of transaminases of unknown origin, as well as any increase in transaminases with a level 3 times or more exceeding the upper limit of the norm;
severe renal impairment with creatinine clearance ≤30 ml / min;
concomitant use of cyclosporine;
during pregnancy and lactation;
Hypersensitivity of the immune system to rosuvastatin or any other component of Crestor;
the drug is not prescribed to patients who do not use highly effective and effective methods of contraception;
myopathy;
dose of Crestor at 40 mg / day is contraindicated in patients with an increased risk of developing rhabdomyolysis or myopathy;
age up to 18 years.

Pregnancy

Crestor is contraindicated for use in pregnant women. If a nursing mother is prescribed, breastfeeding is discontinued. Before treatment with rosuvostatin in women of reproductive age, a pregnancy test should be performed. While taking the drug, you must use adequate methods of contraception.

Interaction with other medicinal products

With the simultaneous use of cyclosporine and rosuvastatin, the AUC of the latter was approximately 7 times higher than the same parameter in healthy volunteers.The simultaneous use of these drugs does not change the plasma concentration of cyclosporine.
At the beginning of treatment and during an increase in the dose of rosuvastatin in patients who simultaneously receive warfarin and other vitamin K antagonists, as in the case of other HMG-Co-A reductase inhibitors, an increase in the INR – International Normalized Ratio – prothrombin time may be observed. Cancellation of rosuvostatin or a decrease in its dosage causes a decrease in INR. When rosuvostatin is combined with vitamin K antagonists, monitoring of the INR (prothrombin time) is recommended.
The simultaneous use of lipid-lowering drugs (for example, hemifibrozil) and rosuvastatin causes an increase in the maximum plasma concentration of rosuvastatin and increases its AUC by 2 times.
The simultaneous use of ezetimibe and rosuvostatin did not cause changes in the maximum plasma concentration of both drugs, as well as the AUC. However, it is not recommended to exclude their pharmacological interactions with the development of side effects.
Pharmacokinetic interaction with fibrates is not expected, but pharmacodynamic interaction is possible.Hemofibrates, gemfibrozil, other fibrates and lipid-lowering doses of nicotinic acid (in a dose equivalent to 1 g / day or more) potentiate the risk of myopathy when taken simultaneously with HMG-CoA reductase inhibitors. This is probably due to the fact that these drugs cause the onset of myopathy when administered as monotherapy. Therefore, with this combination, patients are recommended to first prescribe a dose of Crestor 5 mg / day.
In a pharmacokinetic study in healthy volunteers, the combination of rosuvostatin and a combination agent containing two protease inhibitors (100 mg ritonavor and 400 mg lopinavir) was associated with an approximately 2-fold increase in AUC for Crestor.At the same time, the maximum concentration of rosuvastatin increased by about 5 times. Interactions with other protease inhibitors have not been studied. When prescribing rosuvastatin to HIV-infected patients taking ritonavir / lopinavir while using rosuvastatin, the risk / benefit ratio must be taken into account, especially when the dose is increased or at the beginning of treatment.
The simultaneous administration of erythromycin and rosuvastatin causes a decrease in the AUC of rosuvastatin by 20% and its maximum plasma concentration by 30%.Such an interaction develops in connection with an increase in intestinal motility due to the intake of erythromycin.
The clinical significance of the interaction between antacids and rosuvastatin has not been studied. The simultaneous use of antacids with the inclusion of magnesium hydroxide or aluminum and rosuvastatin causes a decrease in the concentration of the latter in blood plasma by 50%. If antacids are taken 2 hours after rosuvastatin, then this effect is less pronounced.
No clinically significant interaction with digoxin expected.
The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of norgestrel and the AUC of ethinyl estradiol by 34% and 26%, respectively. Therefore, an increase in plasma concentration should be taken into account when taking contraceptives. Pharmacokinetic parameters with the combination of rosuvastatin and drugs for hormone replacement therapy have not been studied, but such an interaction cannot be ruled out. This combination of drugs was widely used during clinical trials – all patients tolerated it well.
The results of a study on the interaction in vivo and in vitro indicate that the active substance of Crestor is neither an inducer nor an inhibitor of enzymes of the cytochrome P450 system. Rosuvastatin is only a weak substrate for the action of these enzymes. No clinically significant interaction was determined between ketoconazole (an inhibitor of CYP 3A4 and CY P 2A6) or fluconazole (an inhibitor of CYP 3A4 and CYP 2A9) and rosuvastatin. The simultaneous administration of itraconazole (an inhibitor of CY P3A4) and rosuvastatin increases the AUC of the latter by 28%, which has no clinical significance.Therefore, no interaction associated with the metabolism of cytochrome P450 is expected.

Overdose

If the dose is exceeded, no specific treatment has been developed. Symptomatic agents and supportive therapy are used. If the dose is exceeded, it is necessary to monitor the hepatic functions and the content of creatine phosphokinase (CPK). The effectiveness of hemodialysis is unlikely.

Form of issue

Tablets of 10; twenty; 40 mg. There are 28 tablets in a blister.

Storage conditions

Store at a temperature not exceeding 30 ° C.Keep out of the reach of children. Dispensed by prescription.

Composition

Active ingredient: rosuvastatin 10 mg.

Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.

Active ingredient: rosuvastatin 20 mg.

Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.

Active ingredient: rosuvastatin 40 mg.

Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.

Optional

When the risk of myopathy or rhabdomyolysis is increased, consideration should be given to the balance between the benefit of treatment and the potential risk; such patients are subject to close medical supervision.If the CPK level rises significantly (5 times or more) even before the start of treatment, you should not take rosuvastatin. Determination of cretin phosphokinase to control the possible development of rhabdomyolysis or myopathy is inappropriate in the presence of other probable factors for an increase in CPK or after intense physical exertion, since this may contribute to an incorrect interpretation of the results obtained. If the initial content of creatine phosphokinase is increased by 5 times or more, the next determination of the enzyme in the blood serum must be carried out at least 5 (maximum – 7) days.You should not start treatment with Crestor if repeated determination shows a high initial level of creatine phosphokinase (5 times more than the upper limit of the norm).
Crestor, like other HMG-CoA reductase inhibitors, should be used with caution in patients with a tendency to develop myopathy / rhabdomyolysis. Risk factors for rhabdomyolysis or myopathy may include: hypothyroidism; renal failure; conditions that cause an increase in the plasma concentration of rosuvastatin; alcohol abuse; age over 70; the presence of hereditary muscle diseases in a family or individual history; myotoxicity provoked by the use of other fibrates or inhibitors of MMC-CoA reductase in history; simultaneous use of fibrates.
If the patient is prescribed Crestor, he must be informed of the obligatory immediate report to the attending physician about all cases of unexpected muscle weakness, muscle pain or spasms, especially if they are accompanied by fever and malaise. In such patients, the level of creatine phosphokinase (CPK) is required. Reception of Krestor should be discontinued if the content of CPK is significantly increased (5 times or more), or with a sharp severity of muscle symptoms that cause constant daily discomfort even with the content of creatine phosphokinase, which has not reached a 5-fold increase.If the signs disappear and the CPK content returns to its original physiological value, consider the possibility of re-taking other inhibitors of HMG-CoA reductase or Crestor at doses lower than the previous ones. Such a patient needs close medical supervision. Routine control of CPK in the absence of signs of rhabdomyolysis or myopathy is inappropriate.
There were no signs of an increase in the effect of Crestor on skeletal muscle during clinical trials with concomitant therapy.Nevertheless, there are reports of an increase in the number of cases of myopathy and myositis in patients who took other HMG-CoA reductase inhibitors against the background of the use of fibric acid derivatives (including when prescribing drugs such as nicotinic acid, gemfibrozil, cyclosporine, inhibitors proteases, azole antifungals, and macrolide antibiotics). Gemfibrozil increases the risk of myopathy when Crestor is combined with some HMG-CoA reductase inhibitors. It is not recommended to prescribe Crestor and gemfibrozil at the same time.It is necessary to carefully assess the ratio of the possible benefits and potential risks when prescribing a combination of niacin, fibrates and Crestor.
Simultaneous administration with rosuvostatin fibrates at a dose of 40 mg is contraindicated.
Rosuvostatin is not recommended for patients with severe acute conditions (for example, with arterial hypotension, trauma, sepsis, during major surgical interventions, severe endocrine, metabolic or electrolyte disturbances, as well as in the case of uncontrolled epilepsy, since these conditions can become risk factors occurrence of rhabdomyolysis / myopathy).
Cases of tubular proteinuria have been observed in patients taking high doses of rosuvastatin (mainly at a dosage of 40 mg / day). Tubular proteinuria was short-term or transient in most cases. This proteinuria was not indicative of the development of acute kidney disease or the progression of an existing one. Patients receiving Crestor at a dosage of 40 mg / day are advised to periodically monitor the functional parameters of the kidneys during the course of taking Crestor (the entire course of therapy).
Skeletal muscle effects such as muscle pain, rhabdomyolysis, or myopathy have been reported with rosuvastatin, especially at doses of about 20 mg / day. However, with the combination of ezetimibe and HMG-CoA reductase inhibitors, rhabdomyolysis has developed in very rare cases.
The safety and efficacy of Crestor in children have not been established. In pediatric practice, the experience of using rosulostatin is limited to a small number of observations (children under 8 years of age and older in the presence of homozygous familial hypercholesterolemia).