Statins

• pravastatin and fluvastatin (hydrophilic) are least likely to be associated with muscular adverse effects 
• simvastatin & atorvastatin (lipophilic) most likely to be associated with muscular adverse effects 
• rosuvastatin is the most potent, followed by atorvastatin

 Contraindications

• active liver disease
• heavy alcohol drinking
• pregnancy
• muscle disorders - increased risk of developing myopathy 
• renal impairment - increased risk of developing myopathy 
• hypothyroidism - increased risk of developing myopathy 

Interactions

Counselling

• patients should be made aware of the risk of myopathy, including rhabdomyolysis, and asked to report promptly any muscle pain, weakness or tenderness, particularly if accompanied by fever, malaise or dark urine
• simvastatin needs to be taken at night - rest can be any time 

CK monitoring

• Routine CK monitoring after initiation is not recommended
• CK should be measured during treatment when clinically indicated – i.e. where there are symptoms of muscle pain or tenderness, muscle weakness or muscle cramps
• Before offering a statin, it is important to confirm if the patient has had persistent generalised unexplained muscle pain associated or not with previous lipid lowering treatment. If the patient has then measure baseline CK before starting a statin
• If CK levels are significantly elevated (> 5 x ULN), re-measure CK after 7 days. If levels remain >5 x ULN, statin treatment should not be started
• If CK are raised 5 x ULN, levels should be remeasured within 5 to 7 days later to confirm the results
• Note: Some Black African and Caribbean’s have elevated baseline levels of CK. This is not a contra-indication to statin therapy. In these patients, after initiation if the CK > 5 x baseline - seek advice
• If symptoms of muscle pain or tenderness, muscle weakness or muscle cramps occur during treatment
  • Rule out common causes (e.g. exercise)
  • Check TFTs (hypothyroidism predisposes to myopathy)
  • Measure CK - If CK elevated > 5 x ULN stop and seek advice - If CK elevated < 5 x ULN, follow the strategy below
    • Monitor carefully by repeating CK level in one month
    • If remains elevated, reduce dose and recheck CK level in one month
    • If still remains elevated consider seeking advice
    • If symptoms continue STOP statin and consult a specialist before re-initiating

 Percentage reduction in LDL cholesterol

* MHRA Advice: Increased risk of myopathy with 80mg simvastatin - only consider in patients with severe hypercholesterolaemia and high risk of cardiovascular complications

 References:

https://bnf.nice.org.uk/interaction/simvastatin-2.html

https://bnf.nice.org.uk/interaction/atorvastatin-2.html

• 1. Jones PJH, Schoeller DA. Evidence ofor diurnal periodicity in human cholesterol synthesis. J Lipid Res 1990;31:667-673
• 2. Lund TM et al. .Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. The American Journal of Cardiology 2002;90 (7): 784-786.
• 3. Plakogiannis R et al. Optimal low-density lipoprotein cholesterol lowering--morning versus evening statin administration. Ann Pharmacother. 2007 Jan;41(1):106-10.
• 4. Scharnagl H et al. Efficacy and safety of fluvastatin-extended release in hypercholesterolemic patients: morning administration is equivalent to evening administration. Cardiology. 2006;106(4):241-8

1. Current Problems in Pharmacovigilance (2004); 30: 1-12.
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3. Drug and Therapeutics Bulletin (2001); 39 (3): 17-21.
4. Prescribers' Journal (1999); 39 (4): 220-21.
5. Baxter K editor. Stockley's Drug Interactions. Statins + macrolides. London: Pharmaceutical Press. Electronic version, 2006. Accessed via http://www.medicinescomplete.com on 11/01/06
6. Summary of Product Characteristics - Crestor. AstraZeneca UK Ltd. Accessed via http://emc.medicines.org.uk on 11/01/06
7. Bayer plc (9th August 2001). Letter re: Lipobay (cerivastatin) - suspension of marketing and distribution.
8. GP notebook
9. NICE
10. BNF
11. NHS : Suggestions for Drug Monitoring in Adults in Primary Care
12. diabetes.org.uk
13. https://bnf.nice.org.uk/interaction/simvastatin-2.html