Simvastatin

Question 1

Drug class?

Answer 1

Statins

Question 2

How does it work?

Answer 2

HMG CoA reductase inhibitor

Question 3

Indications?

Answer 3

• Hypercholesterolaemia
  Treatment of primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet, when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.
  Treatment of homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.
• Cardiovascular prevention
  Reduction of cardiovascular mortality and morbidity in patients with manifest atherosclerotic cardiovascular disease or diabetes mellitus, with either normal or increased cholesterol levels, as an adjunct to correction of other risk factors and other cardioprotective therapy.

Question 4

Contra-indications?

Answer 4

• Active liver disease or unexplained persistent elevations of serum transaminases
• Pregnancy and lactation
• Concomitant administration of potent CYP3A4 inhibitors (agents that increase AUC approximately 5 fold or greater) (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors [e.g. nelfinavir], boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone)
• Concomitant administration of gemfibrozil, ciclosporin, or danazol

Question 5

Side effects?

Answer 5

• nosebleeds
• sore throat
• non-allergic rhinitis
• headache
• nausea
• problems with the digestive system, such as constipation, diarrhoea, indigestion or flatulence
• muscle and joint pain
• hyperglycaemia
• an increased risk of diabetes
• Muscle cramps (test CK).

Question 6

Possible interactions?

Answer 6

• Simvastatin is a substrate of cytochrome P450 3A4. Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy.
• Contraindicated during pregnancy.