Simvastatin
A statin prodrug used to lower LDL cholesterol and the risk of heart attack, stroke and death in people at high cardiovascular risk.
Drug card
- Class
- Statin
- How it works
- Blocking HMG-CoA reductase, so the liver makes less cholesterol
- Used for
- Lowering heart attack, stroke and death in high-risk people
- High LDL cholesterol, including familial forms
- High triglycerides (with diet)
- Known for
- Muscle aches (myalgia)
- Myopathy and rhabdomyolysis, more at the highest dose
- Its name
- -vastatin means a statin (HMG-CoA reductase inhibitor)
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does simvastatin work?
Derived from a product of Aspergillus terreus fermentation and given as an inactive lactone. In the body it is hydrolyzed to simvastatin acid, which blocks HMG-CoA reductase, so the liver expresses more LDL receptors and clears more LDL. It is a CYP3A4 and OATP1B1 substrate, so strong CYP3A4 inhibitors raise its levels sharply.
Like other statins: Statins competitively inhibit HMG-CoA reductase, the enzyme that sets the pace of cholesterol synthesis by turning HMG-CoA into mevalonate. Short of cholesterol, liver cells put more LDL receptors on their surface and take up more LDL from the blood, and the liver releases less VLDL. Plasma LDL cholesterol falls, and with it the risk of heart attack and stroke.
Uses
What is simvastatin used for?
- Lowering heart attack, stroke and death in high-risk people
- High LDL cholesterol, including familial forms
- High triglycerides (with diet)
Side effects
Side effects of simvastatin
- Muscle aches (myalgia)Known for
- Myopathy and rhabdomyolysis, more at the highest doseKnown forSerious
- Acute kidney injury from rhabdomyolysisSerious
- Immune-mediated necrotizing myopathy (rare)Serious
- Raised liver enzymes, rarely liver failureSerious
- Higher blood sugar and HbA1c
- Headache
- Abdominal pain
- Constipation
- Nausea
- Allergic reactions, including angioedemaSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Contraindicated with strong CYP3A4 inhibitors (some azoles, macrolides and antivirals, nefazodone) and with cyclosporine, danazol or gemfibrozil.
- Myopathy risk rises with the highest dose and appears higher in Chinese patients.
- In people taking warfarin, check the INR before starting it and when the dose changes.
- Stop it when pregnancy is recognized; breastfeeding is not recommended during treatment.
Good to know: A lactone prodrug from a fungal fermentation product; its CYP3A4 interactions are serious enough that strong inhibitors are contraindicated.
Remember it
A way to remember it
Statins shut the cholesterol factory, and the liver goes shopping for LDL.
With HMG-CoA reductase blocked, liver cells make less cholesterol and add LDL receptors to pull LDL out of the blood. The harms to watch for are in the muscles (myalgia, rhabdomyolysis) and the liver.
Written for biofideX
Its name
-vastatin means statin (HMG-CoA reductase inhibitor)
Atorvastatin, simvastatin, rosuvastatin and pravastatin block HMG-CoA reductase. WHO files the stem under -stat (enzyme inhibitors); nystatin, an antifungal, is not a statin.
- Every drug name stem
Its class
Statins
Other statins with a card:
Easily mixed up with fibrates and cholesterol absorption inhibitors.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Blood clots and cholesterol
Simvastatin is one of 19 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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