How simvastatin works
Simvastatin is a lipid-lowering drug from the group of statins (also known as HMG-CoA reductase inhibitors). It mainly works by inhibiting the enzyme HMG-CoA reductase, which is required in the liver for the formation of cholesterol.
The body needs cholesterol, among other things, to transport fats in the blood. The body produces around two thirds of the cholesterol it needs in the liver itself, while one third is obtained from food.
If cholesterol levels are too high, it is therefore possible to reduce the amount of cholesterol the body produces itself, but often it also helps to fundamentally change the diet. The production of cholesterol in the liver is a complex process.
It is effectively produced from activated acetic acid, a substance that is often found in cells, via many intermediate steps. An important and speed-determining step in this cholesterol biosynthesis depends on a specific enzyme called “HMG-CoA reductase”.
It is precisely this step that simvastatin inhibits – as a result, its own production is reduced and the cholesterol levels in the blood fall (especially those of the “bad” LDL cholesterol, while those of the “good” HDL cholesterol sometimes even increase).
Absorption, breakdown and excretion
Simvastatin is absorbed quickly after oral administration, but only to a small extent, and is converted into the active form by the liver. The maximum effect of simvastatin occurs about one to two hours after ingestion.
As the body forms cholesterol most intensively during the night, simvastatin is usually taken in the evening. The metabolized simvastatin is mainly excreted in the stool, only a small amount is excreted in the urine.
When is simvastatin used?
Simvastatin is mainly used to treat high blood cholesterol levels (hypercholesterolemia). Before starting therapy, an attempt should always be made to normalize cholesterol levels without medication, for example through a healthy diet, exercise and weight loss.
Simvastatin is also approved for the prevention of cardiovascular complications in patients with coronary heart disease (CHD) or an increased risk of cardiovascular disease (such as diabetes patients) – regardless of the level of cholesterol.
Treatment with statins such as simvastatin is usually long-term.
How simvastatin is used
Simvastatin is taken as a tablet once a day in the evening. The individual dose is determined by the doctor and is based on the individual risk, but is usually between five and 80 milligrams.
Do not stop taking the cholesterol-lowering drug without authorization just because you do not “feel” any effect.
Simvastatin is often combined with other medications, for example with the anion exchanger colestyramine, also a cholesterol-lowering drug, or ezetimibe (cholesterol absorption inhibitor).
What are the side effects of simvastatin?
Side effects rarely occur with simvastatin therapy. These include:
- Anemia, dizziness, headaches
- Muscle weakness, pain, cramps (especially with high doses of simvastatin)
- Gastrointestinal problems, dry mouth, sleep disorders and itching
Muscle pain and discomfort during simvastatin therapy are serious side effects. Have these checked out by a doctor as soon as possible.
What should be considered when taking Simvastatin?
Contraindications
Simvastatin must not be used in the following cases
- active liver disease or an unclear increase in liver enzyme values (serum transaminases)
- concomitant use of strong CYP3A4 inhibitors (see subsection “Interactions”)
- concomitant use of strong inhibitors of the transport protein OATP1B1 (see subsection “Interactions”)
- Pregnant or breastfeeding women
Interactions
- Certain agents against fungal infections: Ketoconazole, itraconazole, fluconazole, voriconazole
- Protease inhibitors: Nelfinavir, boceprivir, telaprevir
- Macrolide antibiotics: Erythromycin, clarithromycin, telithromycin
- OATP1B1 inhibitors: ciclosporin (immunosuppressant), gemfibrozil (lipid-lowering agent), rifampicin (antibiotic)
Other medications that should not be combined due to a possible increase in simvastatin side effects are:
- Danazol (hormone)
- Heart medication and calcium channel blockers (amiodarone, verapamil, diltiazem, amlodipine)
Grapefruit juice should also be avoided during simvastatin therapy. Just one glass of grapefruit juice in the morning causes simvastatin levels to be twice as high as usual the following night – the possible consequence is unexpected side effects.
Age restriction
The treatment of children and adolescents (10 to 17 years) is only carried out in special cases and is subject to certain restrictions to be clarified by the doctor. The use in children under ten years of age has not been investigated.
Pregnancy and breastfeeding
Pregnant women and nursing mothers must not take simvastatin, as the safety of treatment has not been investigated. There are generally no disadvantages for the mother if treatment is discontinued during pregnancy and breastfeeding.
How to obtain medication with simvastatin
Simvastatin is only available on prescription in Germany, Austria and Switzerland and can be obtained from pharmacies.
How long has Simvastatin been known?
After the biosynthesis of cholesterol was elucidated in the early 1950s, it quickly became clear that effective drugs against high cholesterol levels could be produced by inhibiting important key enzymes.
The first inhibitor of the enzyme HMG-CoA reductase, mevastatin, was isolated from a fungus in Japan in 1976. However, this was never brought to market maturity.
In 1979, scientists isolated lovastatin from a mushroom. During the study, synthetically modified variants of lovastatin were also developed, with the compound MK-733 (later simvastatin) proving to be therapeutically more effective than the original substance.
