Lovastatin

Substance from the group of statins.

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

Lovastatin, first approved statin, isolated from fermentation of Aspergillus terreus; simvastatin and pravastatin closely related to lovastatin.

Satin of medium potency with possible LDL reduction dose-dependent: 40 to 45 % and short half-life of 1.1 hours.

Lovastatin and simvastatin are lactones or cyclic esters, as prodrug they must first be hydrolyzed to active substance.

Lovastatin is a lipophilic statin/rapid absorption with maximum concentration after 2-4 hours/strong plasma protein binding of ≥95%

Metabolization: mainly via the CypP450 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! Limited applicability in chronic liver diseases/limited liver function.Lovastatin crosses the placenta and blood-brain barrier in animal experiments.

Elimination mainly via the intestine, only approx. 10% via the kidneys.

Based on and in addition to lifestyle changes (dietary changes, exercise, weight reduction, smoking cessation if necessary) for:

Hypercholesterolemia;

Primary prevention if there is an increased risk of cardiovascular disease (≥10%SCORE2/SCORE2-OP);

Secondary prevention if a cardiovascular disease or serious event is already present.

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. It is known from animal studies that lovastatin penetrates the placental barrier and passes into breast milk.

Women and young girls of childbearing age need effective contraception (note interactions!)

For further information, see specialist information!

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

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

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

Rare are severe NW: 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 reaction, angioedema.

For further information and details, see the technical information!

Enzyme systems/carriers and selection of substances with potential for interaction (inhibition), enhancement of effect and risk of serious adverse effects with concomitant treatment with lovastatin (especially at high doses).

CYP3A4 carrier

• Amiodarone, amlodipine (CYP3A5), aprepitant, cilostazol, cimetidine, clarithromycin, conivaptan, ciclosporin, cobicistat, diltiazem, 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

In addition: no concomitant use with fusidic acid (therapy break for treatment duration plus 7 days).

Caution and low dosage with concomitant use of gemfibrozil, other fibrates, niacin

Coumarin derivatives: prothrombin time may be prolonged.

This information is only a selection! Further interactions must be clarified individually in each case! For further information, see Fachinfo! 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!

The risk is particularly increased in special patient groups with polypharmacotherapy!

Lovastatin (generics) 10 mg, 20 mg, 40 mg, 80 mg

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;1:111-188 (https://doi.org/10.1093/eurheartj/ehz455)