Myalgia while taking statinsBMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e5348 (Published 14 August 2012) Cite this as: BMJ 2012;345:e5348
- Shawarna S Lasker, general practitioner1,
- Tahseen A Chowdhury, consultant in diabetes and metabolism2
- 1Kings Medical Centre, Buckhurst Hill IG9 5LP, UK
- 2Department of Diabetes and Metabolism, Royal London Hospital, London E1 1BB, UK
- Correspondence to: T A Chowdhury
- Accepted 27 June 2012
A 56 year old man with type 2 diabetes complains of uncomfortable muscular aches in the arms. He started taking simvastatin 40 mg daily some months ago and has no other medical history of note.
What you should cover
Explain that myalgia with statins is common, affecting 5-10% of patients in clinical trials of statins.
Assess how severe the symptoms are. Do they affect his quality of life? Some patients may develop mild myalgia with statins but are willing to continue treatment because of the substantial cardiovascular benefits they attain (in diabetic patients, numbers needed to treat to prevent one cardiovascular event is 33).
Explore other causes of the myalgia, such as viral illness or hypothyroidism. Rarer causes, such as polymyositis or polymyalgia rheumatica, can be exacerbated by statins.
Has he started taking any medications that might have interacted with his statin? Coadministration of calcium channel blockers has recently been shown to increase risk of myositis. Other drugs that interact with statins include macrolide antibiotics, ciclosporin, protease inhibitors, fibrates, and amiodarone.
Has he been warned not to ingest grapefruit juice? Grapefruit juice inhibits cytochrome p450, leading to reduced metabolism of statins, therefore increasing the risk of myalgia and myositis.
What you should do
Check serum creatine kinase concentration and thyroid function. A clinically significant raised creatine kinase is defined as a concentration above 10 times the upper limit of normal and is a risk factor for rhabdomyolysis, which is a medical emergency. The statin should be stopped immediately. Modestly raised creatine kinase concentrations (under five times the upper limit of normal) are common and may be related to exercise. A creatine kinase concentration below this level is rarely clinically significant.
If the creatine kinase is not significantly raised, discuss whether he would be willing to try rechallenge with simvastatin at a lower dose. If he is not keen or develops symptoms again, try an alternative statin, such as pravastatin 10 mg or atorvastatin 10 mg.
Consider also that one randomised trial has shown that extended release fluvastatin 80 mg daily in patients with statin intolerance may be effective in reducing myalgic symptoms.1
Low dose statins titrated very slowly may cause fewer myalgic symptoms: treatment with a low dose statin started once weekly and then gradually titrated at monthly intervals has been an effective strategy in some case series of patients with myalgia induced by statins.2
If myalgia recurs with low doses of statin or other statins, try non-statin treatment. The National Institute for Health and Clinical Excellence recommends ezetimibe 10 mg daily monotherapy as an option for the treatment of adults with hypercholesterolaemia who would otherwise be started on a statin but are intolerant. Alternatively, ezetimibe could be combined with the lowest tolerated statin dose to help achieve a target cholesterol concentration.
If ezetimibe is ineffective or not tolerated, use bile acid sequestrants such as Colesevalam 625 mg three times daily, but these may induce adverse gastrointestinal effects.
Plant stanols and sterols supplements have a useful beneficial effect on serum cholesterol but are costly and need to be taken regularly. There are no randomised trials of their use in patients with statin intolerance.
Statin associated necrotising autoimmune myopathy is a rare condition in which discontinuation of the statin does not lead to recovery, and immunosuppression may need to be considered. Referral to a neurologist specialising in myopathy is required.
Heart UK (www.heart.org.uk)—A useful website for patients with high cholesterol
National Institute for Health and Clinical Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. (Clinical guideline 67.) 2008. http://guidance.nice.org.uk/CG67
National Institute for Health and Clinical Excellence. Ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia. (Technical appraisal 132.) 2007. http://guidance.nice.org.uk/TA132
Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol 2008;101:490-6.
Eckel RH. Approach to the patient who is intolerant of statin therapy. J Clin Endocrinol Metab 2010;95:2015-22.
Cite this as: BMJ 2012;345:e5348
This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.
Contributors: All authors contributed equally to the preparation of this manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work .
Provenance and peer review: Not commissioned; externally peer reviewed.