Simvastatin

Substance from the group of statins.

Competitive, reversible inhibition of HMG-CoA reductase, the rate-determining key enzyme of cholesterol synthesis; reduction of endogenous cholesterol synthesis and lowering of total cholesterol and LDL cholesterol levels.

Naturally produced statin, similar to lovastatin

Lipophilic statin of medium potency with maximum possible LDL reduction dose-dependent: 40 to 45 % and half-life of 3 hours.

Simvastatin (lactone or cyclic ester) is a prodrug; is rapidly absorbed after oral administration and rapidly hydrolyzed to active substance in the liver.

Plasma protein binding ≥95%

Metabolization: mainly via the Cyp P 450 system in the liver; mainly via CYP3A4, therefore interaction with other substances and increased risk of myotoxic and other adverse drug reactions (ADR) due to increased effect! (Restriction in liver diseases). Substrate of various transporters (see WW).

Elimination: approx. 13% via kidney approx. 60% via intestine.

SLCO1B1 polymorphism is one of the causes of individual differences in bioavailability and risk of adverse effects.

Substance well investigated in numerous studies and large study population, in particular for effectiveness in cardiovascular risk reduction (see technical info).

Treatment on the basis of and in combination with lifestyle changes (dietary changes, exercise, smoking cessation if necessary) in accordance with guidelines (Mach F et al 2020).

Hypercholesterolemia, dyslipidemia.

Primary prevention: in case of increased risk of cardiovascular disease (≥10% SCORE2/SCORE2-OP).

Secondary prevention: in case of pre-existing cardiovascular disease or a history of serious vascular events.

Homozygous and heterozygous FH (from 10 years of age).

In children, observe age-dependent maximum doses, treatment and monitoring only by a specialist (guideline).

Cholesterol and other intermediate products of cholesterol biosynthesis are essential in embryonic and fetal development and necessary for the synthesis of steroids and cell membranes!

Statins are therefore contraindicated during pregnancy and breastfeeding.

The potential risk of damage justifies a break in therapy

Women and young girls of childbearing age need effective contraception (watch out for interactions!)

In case of unexpected pregnancy during treatment with statins, see Embryotox Charité.

Dosage according to guidelines according to target value with lowest necessary dose, if necessary increase dose slowly at intervals of at least 4-6 weeks; avoid high doses, if necessary start combination therapy (ezetimibe) early, take individual patient factors into account.

Maximum dose of 80 mg simvastatin should not be used due to increased risk of severe myopathy/rhabdomyolysis (SEARCH study) compared to other statins of comparable potency.

Doubling the dose brings only approx. 6% additional LDL-C reduction, but higher risk of side effects as side effects are dose-dependent!

Dosage: orally once daily, independent of food.

Preferably taken in the evening, improved efficacy with a short half-life, as cholesterol synthesis depends on the time of day with the highest cholesterol synthesis at night or early in the morning. If anion exchange resins are used at the same time: take up to 2 hours before or at least 4 hours after.

Important: daily intake time should always be maintained to avoid fluctuations in potency.

Therapy adherence is important and should be discussed with the patient!

Mild side effects are frequent: headache, dizziness, myalgia, gastrointestinal complaints.

Frequent: Deterioration of blood glucose levels, first manifestation of diabetes, especially in predisposed cases (prediabetes, obesity metabolic syndrome)

Severe adverse effects are very rare: myositis, myopathy, rhabdomyolysis (risk of renal failure), hepatotoxic damage, liver values ≥3 times normal; jaundice, weakness, feeling sick and fever.

Individual cases: IMNM; interstitial lung disease (with long-term use).

Hypersensitivity reactions, angioedema.

For further information and details, see the technical information!

Enzymesystems/carriers and selection of substances with potential for interaction (inhibition), enhancement of effect and risk of serious adverse effects with concomitant treatment with simvastatin

CYP3A4: Amiodarone, amlodipine (CYP3A5), aprepitant, cilostazol, cimetidine, clarithromycin, conivaptan, ciclosporin, cobicistat, diltiazem, verapamil, erythromycin, fluconazole (higher doses), fluvoxamine, grapefruit, idelalisib, imatinib, isavuconazole, itraconazole, netupitant, posaconazole, ritonavir, voriconazole

P-gp (ABCB1): Amiodarone, Azithromycin, Captopril, Carvedilol, Quinidine, Cimetidine, Clarithromycin, Colchicine, Conivaptan, Ciclosporin, Diltiazem, Dronedarone (potent), Erythromycin, Itraconazole, Nicardipine, Protease inhibitors (HIV), Ranolazine, Ticagrelor, Verapamil

OATP1B1: carbamazepine, clarithromycin, ciclosporin, erythromycin, gemfibrozil, protease inhibitors (HIV), roxithromycin, sacubitril

BCRP (Breast Cancer Resistance Protein) efflux carrier: Elbasvir, grazoprevir

In addition: Fusidic acid (systemic application): Break in therapy plus 7 days for the duration of use.

For further information and for substances that can be used with dose restrictions, see the technical information.

This information is only a selection! Further interactions must be clarified individually in each case! (for further information, see specialist information or databases on drug interactions).

It should also be noted that statins can alter the effect of concomitant medication and this can also result in additional incompatibilities!

Interaction studies have only been carried out in adults.

Especially in special patient groups with polypharmacotherapy, the risk of side effects is increased!

Hypersensitivity to the active substance or one of the ingredients.

Active liver disease or unclear persistent elevation of serum transaminases.

Pregnancy and lactation

Concomitant use of potent CYP3A4 inhibitors (substances that increase AUC at least 5-fold) (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and medicines containing cobicistat).

Concomitant use of gemfibrozil, ciclosporin or danazol

Concomitant use of lomitapide and simvastatin in doses of more than 40 mg in patients with homozygous familial hypercholesterolemia

Simvastatin (^Zocor®, generics) 5 mg, 10 mg, 20 mg, 40 mg

The therapeutic success of topical but also systemically applied simvastatin in segmental vitiligo is remarkable (Niezgoda A et al. 2024).

1. Mach F et al (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) European Heart Journal 41:111-188

2. Niezgoda A et al.(2024) Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study. Sci Rep 14:14612.

3. Wang D et al. (2023) Association between statins exposure and risk of skin cancer: an updated meta-analysis. Int J Dermatol 62:1332-1344.

4. Expert information Simvastatin 10/20/40/80
5. Expert information Simvastatin 30/60
6. Expert information Simvastatin/Ezetimibe
7. Specialist information Simvastatin dura