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Statin-Induced Myopathy

Aka: Statin-Induced Myopathy, Rhabdomyolysis due to Statin, Statin-Induced Myalgias, Myositis due to Statins, Statin Myopathy, Statin Intolerance
  1. See Also
    1. Statin
  2. Epidemiology
    1. Statin-Induced Myalgias are common (5-30%)
    2. Statin-induced Rhabdomyolysis is very uncommon (<0.01%)
      1. Davidson (2006) Am J Cardiol 97(8A):32C–43C [PubMed]
      2. Mendes (2014) Physiother Can 66(2): 124–132 [PubMed]
  3. Mechanism
    1. Typical Myopathy
      1. Muscle injury secondary to Statin use (drug-induced Myopathy - accelerating Muscle Cell death)
    2. Statin-Induced Immune-mediated Necrotizing Myopathy
      1. Newly defined in 2011
      2. Symptoms and findings (including CPK) remain abnormal after stopping the Statin
  4. Symptoms
    1. Myalgia
      1. Muscle ache or weakness with normal CPK
    2. Myostitis
      1. Muscle ache or weakness with CPK elevated but <10 fold increase above normal
    3. Rhabdomyolysis
      1. Muscle ache or weakness with CPK elevated but >10 fold increase above normal
  5. Symptoms: Red Flags
    1. Patient should stop Statin and contact physician if following symptoms experienced
    2. Severe myalgias
    3. Muscle Weakness
    4. Dark Urine
  6. Labs
    1. Creatine Phosphokinase (CPK)
      1. Poor marker for myalgias (only increased in Myositis or Rhabdomyolysis)
      2. Normal in most patients despite myalgias
      3. Abnormal CPK suggests Myositis or Rhabdomyolysis and requires immediate cessation of Statin
    2. Additional labs in CPK Elevation (especially Rhabdomyolysis)
      1. Urine Myoglobin
      2. Renal Function
    3. Labs to consider in differential diagnosis
      1. Vitamin D Level
      2. Thyroid Stimulating Hormone (TSH)
  7. Differential Diagnosis
    1. See Myopathy Causes
    2. Vitamin D Deficiency
    3. Hypothyroidism
  8. Risk factors: Statin induced Myopathy
    1. Statin combination with Gemfibrozil (and to a lesser extent with Fenofibrate)
    2. Drug Interactions (see Statins)
      1. Raised serum Statin levels result in higher myalgia or Myositis risk
    3. Older patients over age 70 years
    4. Low body weight
    5. Female gender
    6. Acute illness or major surgery
    7. Alcohol Abuse or other Substance Abuse (e.g. Cocaine, Amphetamines)
    8. Hypothyroidism
    9. Chronic Kidney Disease Stage 4 (Creatinine Clearance <30 ml/min)
    10. High dose Statin use (dose greater than 50% of maximum dose, especially Simvastatin 80 mg)
  9. Management: Symptomatic Statin-Induced Myalgias and Statin Intolerance
    1. Background
      1. More than 70% of Statin-intolerant patients find a tolerable Statin regimen
      2. Strategies here may also apply to other Statin Intolerance causes (beyond myalgias)
    2. Coenzyme Q10 (Ubiquinone) 100 mg orally daily
      1. Reduces myalgias by 40% in one study (other studies show no efficacy)
      2. Caso (2007) Am J Cardiol 99:1409-12 [PubMed]
    3. Decrease Statin dose by 50%
    4. Consider alternate day dosing or twice weekly dosing of a higher potency Statin (e.g. Rosuvastatin, Atorvastatin)
      1. May lower LDL 30% of baseline when consistently followed, but other options are preferred
    5. Consider Ezetimibe as an adjunct to allow lowering Statin dose
    6. Consider other causes (e.g. Hypothyroidism, Vitamin D Deficiency, Fibromyalgia)
      1. See Myopathy Causes
    7. Consider a trial off Statin for 4-6 weeks
      1. If myalgias persist, Statin was unlikely to be the cause
    8. Consider Drug Interactions and other predisposing medications
      1. See CYP3A3/4 Inhibitor
      2. Fibrates (e.g. Gemfibrozil, Fenofibrate)
      3. Colchicine
      4. Verapamil
      5. Corticosteroids
    9. Consider change to alternative Statin
      1. Initially thought that hydrophilic Statins (Pravastatin, Rosuvastatin) were less likely to cause myalgias
      2. Hydrophilic Statins do not appear to offer any increased benefit over other Statins regarding myalgia risk
        1. Thompson (2003) JAMA 289(13): 1681-90 [PubMed]
    10. References
      1. (2022) Presc Lett, August Issue, accessed online 8/2/2022
      2. Cheeley (2022) J Clin Lipidol +PMID: 35718660 [PubMed]
  10. References
    1. Bruckert (2005) Cardiovasc Drugs Ther 19(6): 403-14 [PubMed]
    2. Graham (2004) JAMA 292(21): 2585-90 [PubMed]
    3. Phillips (2002) Ann Intern Med 137:581-5 [PubMed]

Myositis (C0027121)

Definition (MSH) Inflammation of a muscle or muscle tissue.
Definition (MSHCZE) Zánět svalu nebo svalové tkáně. R
Definition (MEDLINEPLUS)

Myositis means inflammation of the muscles that you use to move your body. An injury, infection, or autoimmune disease can cause it. Two specific kinds are polymyositis and dermatomyositis. Polymyositis causes muscle weakness, usually in the muscles closest to the trunk of your body. Dermatomyositis causes muscle weakness, plus a skin rash.

Other symptoms of myositis may include

  • Fatigue after walking or standing
  • Tripping or falling
  • Trouble swallowing or breathing

Doctors may use a physical exam, lab tests, imaging tests and a muscle biopsy to diagnose myositis. There is no cure for these diseases, but you can treat the symptoms. Polymyositis and dermatomyositis are first treated with high doses of a corticosteroid. Other options include medications, physical therapy, exercise, heat therapy, assistive devices, and rest.

NIH: National Institute of Neurological Disorders and Stroke
Definition (SCTSPA) Inflamación del músculo esquelético; no incluye la inflamación del músculo cardíaco
Definition (SNOMEDCT_US) Inflammation of skeletal muscle, not including inflammation of cardiac muscle
Definition (NCI_CTCAE) A disorder characterized by inflammation involving the skeletal muscles.
Definition (NCI) An inflammatory process affecting the skeletal muscles. Causes include infections, injuries, and autoimmune disorders.
Definition (CSP) inflammation of skeletal muscle.
Concepts Disease or Syndrome (T047)
MSH D009220
ICD10 M60, M60.9, G72.49
SnomedCT 203110007, 268108002, 26889001, 128496001
English Myositides, Myositis unspecified, Myositis, unspecified, MYOSITIS, INFLAMM MUSCLE DIS, MUSCLE DIS INFLAMM, INFLAMM MYOPATHY, MYOPATHY INFLAMM, inflammatory myopathy, inflammatory myopathy (diagnosis), Inflammatory Muscle Disease, Inflammatory Muscle Diseases, Muscle Disease, Inflammatory, Muscle Diseases, Inflammatory, Inflammatory Myopathies, Inflammatory Myopathy, Myopathies, Inflammatory, Myopathy, Inflammatory, Inflammatory myopathy NOS, Myositis [Disease/Finding], Myositis, Unspecified myositis, inflammation of the skeletal muscle, inflammatory muscle disease, inflammatory muscle diseases, myositis nos, Inflammation;muscle(s), muscle inflammation, inflammatory myopathies, myositis (diagnosis), Myositis NOS, Myositis unspecified (disorder), Inflammatory disorder of muscle (disorder), Inflammatory disorder of muscle, Inflammatory myopathy, Myositis (disorder), myositis, disease (or disorder); muscle, inflammatory, inflammation; muscle, inflammatory; myopathy, muscle; disease, inflammatory, muscle; inflammation, myopathy; inflammatory, Myositis, NOS, Muscle inflammation, inflammation of the muscle(s)
French MYOSITE, Inflammation musculaire, Myosite, Maladies inflammatoires des muscles, Myopathie inflammatoire
Portuguese MIOSITE, Inflamação muscular, Miosite, Miopatia Inflamatória
Spanish MIOSITIS, Inflamación muscular, miositis, no especificada, miositis, no especificada (trastorno), miopatía inflamatoria (trastorno), miopatía inflamatoria, miositis (trastorno), miositis, trastorno muscular inflamatorio, Miositis, Miopatía Inflamatoria
German MYOSITIS, Muskelentzuendung, Myositis, nicht naeher bezeichnet, Myositis, Entzündliche Myopathie, Muskelentzündung
Dutch spierontsteking, aandoening; spier, inflammatoir, inflammatoir; myopathie, myopathie; inflammatoir, ontsteking; spier, spier; aandoening, inflammatoir, spier; ontsteking, Myositis, niet gespecificeerd, myositis, Inflammatoire myopathie, Myositis
Italian Infiammazione muscolare, Malattie infiammatorie dei muscoli, Miopatie infiammatorie, Miosite
Japanese 筋肉の炎症, ｷﾝｴﾝ, ｷﾝﾆｸﾉｴﾝｼｮｳ, 筋炎, 筋肉炎
Swedish Muskelinflammation
Czech myozitida, zánětlivé nemoci svalů, svaly - zánět, zánětlivá myopatie, Zánět svalu, Myozitida, zánět svalu, zánětlivé myopatie
Finnish Myosiitti
Russian MIOZIT, МИОЗИТ
Korean 근육염, 상세불명의 근육염
Croatian UPALA MIŠIĆA, MIOZITIS
Polish Zapalenie mięśni eozynofilowe, Zapalenie mięśni
Hungarian Myositis, Izomgyulladás
Norwegian Inflammatorisk myopati, Myositt, Muskelsykdommer, inflammatorisk, Myopati, inflammatorisk, Inflammatoriske muskelsykdommer
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Hydroxymethylglutaryl-CoA Reductase Inhibitors (C0360714)

Definition (CHV) cholesterol lowering drug
Definition (MEDLINEPLUS)

Statins are drugs used to lower cholesterol. Your body needs some cholesterol to work properly. But if you have too much in your blood, it can stick to the walls of your arteries, narrowing or even blocking them.

If diet and exercise don't reduce your cholesterol levels, you may need to take medicine. Often, this medicine is a statin. Statins interfere with the production of cholesterol in your liver. They lower bad cholesterol levels and raise good cholesterol levels and can slow the formation of plaques in your arteries.

Statins are relatively safe for most people. But they are not recommended for pregnant patients or those with active or chronic liver disease. They can also cause serious muscle problems. Some statins also interact adversely with other drugs. You may have fewer side effects with one statin drug than another.

Researchers are also studying the use of statins for other conditions.

Food and Drug Administration
Definition (NCI_NCI-GLOSS) Any of a group of drugs that lower the amount of cholesterol and certain fats in the blood. Statins inhibit a key enzyme that helps make cholesterol. Statin drugs are being studied in the prevention and treatment of cancer.
Definition (NCI) Any substance that inhibits HMG-CoA reductase, a key enzyme in cholesterol synthesis. Inhibition of HMG-CoA reductase acts to lower plasma cholesterol and lipoprotein levels.
Definition (MSH) Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D019161
SnomedCT 372912004, 96302009
English HMG CoA Reductase Inhibitors, HMG-CoA Reductase Inhibitors, Inhibitors, HMG-CoA Reductase, Reductase Inhibitors, HMG-CoA, Hydroxymethylglutaryl CoA Reductase Inhibitors, Hydroxymethylglutaryl-CoA Inhibitors, Hydroxymethylglutaryl-Coenzyme A Inhibitors, Inhibitors, HMG CoA Reductase, Inhibitors, Hydroxymethylglutaryl CoA, Inhibitors, Hydroxymethylglutaryl Coenzyme A, Inhibitors, Hydroxymethylglutaryl-CoA, Inhibitors, Hydroxymethylglutaryl-CoA Reductase, Inhibitors, Hydroxymethylglutaryl-Coenzyme A, Reductase Inhibitors, Hydroxymethylglutaryl-CoA, Statin, 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, INHIB HMG COA REDUCTASE, INHIB HYDROXYMETHYLGLUTARYL COA, HMG COA REDUCTASE INHIB, HYDROXYMETHYLGLUTARYL COA REDUCTASE INHIB, HMG-CoA reductase inhibitors (medication), HMG-CoA reductase inhibitors, statin, Hydroxymethylglutaryl-coenzyme A reductase inhibitor, HMG-CoA reductase inhibitor (product), Hydroxymethylglutaryl-coenzyme A reductase inhibitor (product), 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (substance), 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (substance), HMG-CoA Statins, Statins, HMG CoA, Statins, HMG-CoA, hydroxymethylglutaryl-coenzyme A reductase inhibitor, HMG COA reductase inhibitor, HMG-CoA reductase inhibitor, Statins, HMG-CoA reductase inhibitor, NOS, HMG-CoA reductase inhibitor (substance), HMG-CoA Reductase Inhibitor, Hydroxymethylglutaryl CoenzymeA Reductase Inhibitors, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) Reductase Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors
Spanish inhibidor de la HMG - CoA reductasa, inhibidor de 3-hidroxi-3-metilglutaril coenzima A reductasa, inhibidor de 3-hidroxi-3-metilglutaril coenzima A reductasa (sustancia), inhibidor de la HMG - CoA reductasa (sustancia), inhibidor de hidroximetilglutaril coenzima A reductasa, inhibidor de hidroximetilglutaril coenzima A reductasa (producto), inhibidor de la HMG-CoA reductasa (producto), inhibidor de la HMG-CoA reductasa (sustancia), inhibidor de la HMG-CoA reductasa, estatina, inhibidor de la 3-hidroxi-3-metilglutaril coenzima A reductasa, Estatinas HMG-CoA, Inhibidores de Hidroximetilglutaril-CoA Reductasas, Inhibidores de HMG CoA Reductasa
French Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase, Inhibiteurs de l'hydroxyméthylglutaryl-Coenzyme A réductase, Inhibiteurs de l'HMG-CoA réductase, Statines
Swedish Hydroximetylglutaryl-CoA-reduktashämmare
Czech HMG-CoA-reduktasa - inhibitory, statiny, inhibitory 3HMG CoA-reduktázy, hydroxymethylglutaryl-CoA-reduktasa - inhibitory
Finnish Hydroksimetyyliglutaryyli-KoA-reduktaasin estäjät
Russian GIDROKSIMETILGLUTARIL-KOA-REDUKTAZY INGIBITORY, HMG-COA REDUKTAZY INGIBITORY, GMG-KOA REDUKTAZY INGIBITORY, STATINY GMG-KOA-REDUKTAZY, HMG-COA-РЕДУКТАЗЫ СТАТИНЫ, СТАТИНЫ ГМГ-КОA-РЕДУКТАЗЫ, HMG-COA-REDUKTAZY STATINY, HMG-COA РЕДУКТАЗЫ ИНГИБИТОРЫ, ГИДРОКСИМЕТИЛГЛУТАРИЛ-КОA-РЕДУКТАЗЫ ИНГИБИТОРЫ, ГМГ-КОA РЕДУКТАЗЫ ИНГИБИТОРЫ
Japanese ヒドロキシメチルグルタリルCoAレダクターゼ抑制剤, ヒドロキシメチルグルタリル-CoAレダクターゼ阻害剤, ヒドロキシメチルグルタリルCoAレダクターゼ阻害剤, HMG-CoA還元酵素阻害剤, HMG-CoAレダクターゼ抑制剤, HMG-CoAレダクターゼ阻害剤, HMG-CoAレダクターゼインヒビター, HMG-CoA還元酵素阻害薬
Polish Statyny, HMG-CoA, Inhibitory reduktazy hydroksymetyloglutarylo CoA, Inhibitory reduktazy HMG-CoA, Inhibitory reduktazy 3-hydroksy-3-metyloglutarylo-koenzymu A
German HMG-CoA-Reduktase-Inhibitoren, Hydroxymethylglutaryl-CoA-Reductase-Inhibitoren, Hydroxymethylglutaryl-CoA-Reduktase-Inhibitoren, Inhibitoren, HMG-CoA Reduktase, Inhibitoren, Hydroxymethylglutaryl-CoA, Inhibitoren, Hydroxymethylglutaryl-Coenzym A, Statine, HMG-CoA
Italian Inibitori della reduttasi del coenzima A idrossimetilglutarilico
Portuguese Estatinas de HMG-CoA, Inibidores de Hidroximetilglutaril-CoA Redutases, Inibidores de HMG-CoA Redutases
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Drug-induced myopathy (C0410220)

Concepts Pathologic Function (T046)
ICD10 G72.0
SnomedCT 193242006, 240101000
German Arzneimittelinduzierte Myopathie
Korean 약물유발성 근육병증
English drug induced myopathy, drug-induced myopathy, drug-induced myopathy (diagnosis), Drug-induced myopathy, Drug-induced myopathy (disorder), drugs; myopathy, myopathy; drugs
Dutch geneesmiddel; myopathie, myopathie; geneesmiddelen, Myopathie ten gevolge van geneesmiddelengebruik
Spanish miopatía inducida por drogas (trastorno), miopatía inducida por drogas
Sources
Derived from the NIH UMLS (Unified Medical Language System)


drug-induced rhabdomyolysis (C2200329)

Concepts Pathologic Function (T046)
English drug-induced rhabdomyolysis (diagnosis), drug-induced rhabdomyolysis
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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