These results were similar to those of previous reports of statininduced. Current knowledge of the pharmacology of the hmgcoa reductase inhibitors and the drug interactions that potentiate these adverse effects are discussed. Musculoskeletal symptoms may be present in only half of cases. As well as inhibiting the conversion of hmgcoenzyme a to mevalonic acid, statins can also inhibit the synthesis of coenzyme q10 ubiquitone.
Between january 1990 and march 2002, the fda medwatch system reported 3339 cases of statin associated rhabdomyolysis 1, 3. Mar 01, 2002 rhabdomyolysis is a potentially lifethreatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. Statin induced myopathy sivakumar sathasivam, bryan lecky since their introduction for the treatment of hypercholesterolaemia in 1987, the use of statins has grown to over 100 million prescriptions per year. Expert opinion9 suggests that this is unnecessary in most cases and a clinical approach to management, as outlined above, is more appropriate. This chapter describes the clinical characteristics, evaluation, and management of statin. Treatment involves immediate discontinuation of the statin, and hydration. Rhabdomyolysis occurring in solid organ transplant recipients after the concomitant use of cyclosporine and a statin have been described. It is one of many types of rhabdomyolysis that can occur, and because of this the exact prevalence and incidence are unclear. Jul 11, 2017 if rhabdomyolysis is the culprit, statin treatment will be stopped immediately. In the majority of situations, creatine kinase will be normal or only mildly elevated. Statinassociated rhabdomyolysis is a serious adverse event with a very low incidence and is considered the most severe of the musclerelated side effects of the statins. Statininduced rhabdomyolysis sachinkumar n ambapkar1, naresh shetty2, arpita dwivedy3 introduction s tatins have become the most widely prescribed drug worldwide since its introduction in 1987. Rhabdomyolysis though rare is the most severe form of myotoxicity, which can occur with.
The patient noticed progressive proximal muscle weakness after two cycles of palbociclib, with no other. Hmgcoa reductase inhibitors, or statin drugs, are the primary pharmacologic treatment for hypercholesterolemia worldwide. Nausea and vomiting, abdominal pain, tachycardia in. Statininduced rhabdomyolysis was more commonly reported when statins were used in conjunction with other drugs, which potentiated its effect. We describe a case of simvastatininduced rhabdomyolysis. The mainstay of treatment consists of cessation of statins. Clinically significant statininduced rhabdomyolysis is an uncommon but lifethreatening adverse effect. Clinical perspectives of statininduced rhabdomyolysis american. Immunemediated necrotizing myopathy associated with statin use and antihmgcr antibodies was first described in 2010 by christopherstine et al.
As the incidence of statininduced rhabdomyolysis is rare, the opportunity for a randomized control trial is minimal. Statin associated rhabdomyolysis is a serious adverse event with a very low incidence and is considered the most severe of the musclerelated side effects of the statins. Persistent muscular problems or raised creatine kinase after statins have been withdrawn. Brown urine, as a result of myoglobinuria, and acute renal failure are suggestive of rhabdomyolysis. Rhabdomyolysis and statins why statin drugs can put you. Although rhabdomyolysis associated with statin treatment is very rare less than one fatal case per 5 million patients, nevertheless muscular pain and weakness are more frequent and may affect 7% of patients on statin monotherapy, with myalgia contributing up to 25% of all adverse events associated with statin use. Exertional rhabdomyolysis er is the breakdown of muscle from extreme physical exertion. Over 150 agents have been associated with rhabdomyolysis. Mechanism of statininduced rhabdomyolysis request pdf. Rhabdomyolysis is the most severe clinical manifestation of statin induced myopathy and can be lifethreatening. It is important to differentiate toxic statin myopathy from statininduced autoimmune myopathy table 1. Jan 14, 2020 however, the risk of developing rhabdomyolysis from statin therapy is very low, around 1. A 60 to 65yearold female on prior statin therapy was initiated on palbociclib and fulvestrant for the treatment of metastatic, hormonereceptor positive breast cancer.
Normally, statin therapy is monitored by measuring serum creatine kinase in presence of appropriate clinical symptoms. Statinassociated muscle symptoms sams are the most clinically relevant adverse effects of statin therapy as they reduce quality of life, can trigger complications as severe as rhabdomyolysis, and lessen adherence to statin therapy. Long school of pharmacy, university of the pacific, stockton, ca 3department of pharmacology, louisiana state university. As the incidence of statin induced rhabdomyolysis is rare, the opportunity for a randomized control trial is minimal. Rhabdomyolysis is a rare 1 in 20 000 patients and severe. The case report demonstrates the successful use of an alternative statin after a statin related episode of rhabdomyolysis.
Rhabdomyolysis associated with statin therapy has an incidence of 3. Research is needed to identify the role of exercise and. Statin induced necrotizing autoimmune myopathy sinam, a subtype of inflammatory myopathy, is an exceedingly rare but severe side effect of statin use that manifests as progressive muscle weakness. Secondly, the presence of abnormal prenylated protein causes an. Rhabdomyolysis and statins why statin drugs can put you in. The statin treat ment reduced the contractility of the cultured myofibers and made them vulnerable to caffeineinduced contraction, resulting in cell damage 15. Risk factors and drug interactions predisposing to statin. Cureus a rapidly progressive case of statininduced. Statin induced rhabdomyolysis sachinkumar n ambapkar1, naresh shetty2, arpita dwivedy3 introduction s tatins have become the most widely prescribed drug worldwide since its introduction in 1987. A 74yearold man, treated with atorvastatin, developed rhabdomyolysis after the coadministration of fusidic acid and flucloxacillin. Druginduced myopathy ranges from mild myalgias with or without mild weakness to chronic myopathy with severe weakness and to massive rhabdomyolysis with acute renal failure. At least 5% of patients taking statins have statinassociated muscle symptoms sams. Statins are one of the most commonly used medications to lower cholesterol and have been known to cause various side effects including myalgias, myopathies, and rhabdomyolysis. Clinically significant statin induced rhabdomyolysis is an uncommon but lifethreatening adverse effect.
For such patients, rechallenge with the same statin at a lower dose will often result in the patient continuing treatment without future myotoxicity. Thus, carefully documented caseseries will be required to help understand some of the important questions. Request pdf on feb 24, 2020, min chul kim and others published image of statininduced rhabdomyolysis find, read and cite all the research you need on researchgate. Rhabdomyolysis is a welldocumented side effect of statin therapy. Frequent monitoring of cpk is necessary for early diagnosis of such complication. Both the fda and the uk medicines and healthcare products regulatory agency state that simvastatin is contraindicated in patients taking clarithromycin. The mortality risk from rhabdomyolysis is approximately 0. The national lipid association estimated that rhabdomyolysis occurs at a. The symptoms of these effects range from slight myalgia to severe rhabdomyolysis. Discussion daptomycin induced rhabdomyolysis is a known possible complication and warrants high level of awareness due to lifethreatening potential. While statin drugs are not the only reason for rhabdomyolysis, rhabdomyolysis and statins is a rare but very real problem that can devastate the person affected who may end up with permanent statin drug muscle weakness and muscle pain from the damage that these drugs do. Current knowledge of the pharmacology of the hmgcoa reductase inhibitors and the drug interactions that potentiate these adverse effects are. The mortality rate associated with statin induced rhabdomyolysis is approximately 0.
She subsequently developed sudden progressive muscle weakness that progressed to death within weeks. Rhabdomyolysis is a rare adverse effect of the statins occurring in fewer than 0. Fatal statininduced rhabdomyolysis has an incidence of 0. The identification of patients with an increased proclivity. The patient experienced a myocardial infarct 1 y after the episode of. Additionally, a doseresponse relationship exists with higher statin doses resulting in increased frequency of rhabdomyolysis 11. The greatest risk was with the use of cerivastatin, which was withdrawn from the market in 2001, after 31 rhabdomyolysis deaths reported in elderly patients who used it in association with the gemfibrozil. All statins increase a patients chances of developing myositis and rhabdomyolysis, potentially fatal conditions that cause muscle pain and muscle deterioration and may lead to kidney failure.
Aki is a serious complication of rhabdomyolysis and a recent case described a patient requiring haemodialysis for statin induced rhabdomyolysis after being prescribed clarithromycin. Successful reintroduction of statin therapy after statin. Sideeffects of statin use and focus on rhabdomyolysis. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. Drug induced myopathy may result from several different mechanisms. The risk of statin induced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. The patient was a 77yearold female admitted to a transitional care unit tcu following an acute hospitalization for statininduced rhabdomyolysis caused by cholesterol lowering medications.
Introduction rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle. Other investigations should include thyroid function tests, since hypothyroidism can cause hypercholesterolaemia and elevated ck, and can predispose a patient to statininduced myopathy. Doseindependent daptomycin associated rhabdomyolysis. Although the precise incidence is unknown, druginduced myopathy is among the most common causes of muscle disease. Coenzyme q10 ubiquinone levels are decreased in statin use. Where patients do not recover despite cessation of statin therapy muscle biopsy might be indicated. Nov 15, 20 in 19 cases, the patient was referred to rehabilitation, but the case reports do not include descriptions of the treatment. Urine from a person with rhabdomyolysis showing the characteristic brown discoloration as a result of myoglobinuria. To identify case reports of statininduced rhabdomyolysis and. Myalgia, stiffness, weakness, malaise, lowgrade fever, dark urine. Statininduced autoimmune myopathy is treated with steroids, intravenous immunoglobulin, or immunotherapy, plasmapheresis and so on. Rhabdomyolysis is a rare but lifethreatening complication of statin therapy. The pathophysiology involves injury to the myocyte membrane andor altered energy production that results in increased intracellular calcium concentrations and initiation of destructive processes. Coq10 supplements are sometimes used to treat statinassociated myopathy, though evidence of their efficacy is lacking as of 2017.
We describe a case of simvastatin induced rhabdomyolysis. Rhabdomyolysis or milder forms of muscle inflammation from statins can be diagnosed with a blood test measuring levels of the enzyme creatinine kinase. Statin associated rhabdomyolysis is a serious adverse event with averylow incidence and is considered the most severe of the musclerelated side effects of the statins. The case report demonstrates the successful use of an alternative statin after a statinrelated episode of rhabdomyolysis. Frontiers fatal statininduced rhabdomyolysis by possible. All clinicians should be aware of common causes, diagnosis, and treatment options. Risk of statininduced rhabdomyolysis in patients with. Renal function and electrolytes should be carefully monitored, because there is a risk of aki, hyperkalemia and metabolic acidosis. Rhabdomyolysis and statin myopathy are discussed in detail separately. Statin induced rhabdomyolysis may result from a variety of mechanisms. While in most cases myopathy caused by statins is mild and can be reversed when the medication is discontinued, it may present as rhabdomyolysis or severe muscle damage as in the case mentioned. According to the fda, the chances of developing myositis or rhabdomyolysis from statins are low. Rhabdomyolysis is a wellknown clinical syndrome of muscle injury associated with myoglobinuria, electrolyte abnormalities, and often acute kidney injury aki. Statininduced necrotizing autoimmune myopathy sinam, a subtype of inflammatory myopathy, is an exceedingly rare but severe side effect of statin use that manifests as progressive muscle weakness.
Muscle coenzyme q10 level in statinrelated myopathy. Presymptomatic neuromuscular disorders disclosed following statin treatment. Statin therapy associated with fatal rhabdomyolysis. Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. The effect of simvastatin treatment on natural antioxidants in lowdensity. Typical of hmgcr antibodymediated imnm is the ongoing muscle weakness and elevated ck despite discontinuation of the statin. Apr 25, 2014 the incidence of rhabdomyolysis from all causes is 1. The incidence of rhabdomyolysis from all causes is 1. If rhabdomyolysis is the culprit, statin treatment will be stopped immediately. At least 5% of patients taking statins have statin associated muscle symptoms sams.
Request pdf mechanism of statininduced rhabdomyolysis statins, a group of drugs used for the treatment of hypercholesterolemia, have adverse effects on skeletal muscle. Rhabdomyolysis after concomitant use of cyclosporine and. Mechanisms of statininduced myopathy arteriosclerosis. Simvastatininduced rhabdomyolysis followed by a melas syndrome. The risk of statininduced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. In the united states, deaths from rhabdomyolysis induced by statins occur in about 0. Statins, a group of drugs used for the treatment of hypercholesterolemia, have adverse effects on skeletal muscle. Jul 17, 2017 approximately 60% of cases of statininduced rhabdomyolysis are due to concomitant administration of a cyp3a4 inhibitor 810.
Full recovery can be expected with early diagnosis and treatment of the many complications that can develop in patients with this syndrome. Statininduced rhabdomyolysis is well described,1 although the causative mechanism has not been clearly established. Sams may seriously impair quality of life and cause complications of variable severity, up to and including rhabdomyolysis in about 1 in 100 000 cases. The patient recovered with supportive treatment and subsequently tolerated reintroduction of atorvastatin. The number of patients currently taking statins is estimated to be several millions worldwide.
See causes of rhabdomyolysis and clinical manifestations and diagnosis of rhabdomyolysis and statin musclerelated adverse events. Severe rhabdomyolysis as a consequence of the interaction. Medline, cinahl, scopus, and pedro databases were searched 199020 for relevant case reports using the search terms statins. Research is needed to identify the role of exercise and rehabilitation following statininduced rhabdomyoloysis since muscle damage may be severe and may have longterm effects on muscle function. Since their introduction for the treatment of hyper cholesterolaemia in 1987, the use of statins has grown to over 100 million prescriptions per year. Firstly an unstable skeletal muscle cell membrane due to a blockage in the synthetic pathway for cholesterol, which results subsequently in a low intramembranous cholesterol content. Managing statininduced myopathy pharmaceutical journal. In the united states, an estimated 38 million people took. Mechanism of statininduced rhabdomyolysis sciencedirect.
To identify case reports of statininduced rhabdomyolysis and summarize common predisposing factors, symptoms, diagnostic findings, functional outcomes, characteristics, treatment, and rehabilitation. Implementation consortium cpic guidelines recommend a lower svt. Medline, cinahl, scopus, and pedro databases were searched 199020 for relevant case reports using the search terms statins, rhabdomyolysis, myalgia. Statininduced rhabdomyolysis may result from a variety of mechanisms.
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