Rosuvastatin

Substance from the group of statins.

Mode of action: 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.

Hydrophilic statin.

HWZ: 20 hours.

Highly effective statin with max. possible LDL reduction dose-dependent: 56 to 60 %.

Statin with very low metabolization via the Cyt P 450 system in the liver, here mainly by CYP2C9 and CYP2C19 and predominantly excretion unchanged via the kidneys. Therefore, do not use in case of impaired renal function.

Doses up to 40 mg can be used in cases of mild renal impairment, doses of ≥40 mg are contraindicated. All doses are contraindicated in severe renal impairment! (see technical information).

Applicable in chronic liver disease, e.g. also non-alcoholic or metabolic fatty liver disease (increased cardiovascular risk)(rosuvastatin and pravastatin applicable).

Bioavailability not restricted up to Child-Pugh score 7. Contraindicated in active liver disease!

Increased bioavailability in patients of Asian descent! Starting dose 5 mg; doses above 40 mg contraindicated!

Genetic polymorphisms possible: genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA are associated with increased exposure to rosuvastatin. In patients with genotype c.521CC or c.421AA, use only half of the usually recommended dose and max. dose of 20 mg (see expert information).

Caution in patients with pre-existing myopathy, if used only with dosage restriction!

Can also be used in HIV patients, as low metabolization via Cyt P450 and low interaction potential with HIV medication (clarify in individual cases!, lowest possible dose, dose limit 10 mg).

Excretion approx. 90% unchanged via the intestine, the rest via the kidneys. The OATP-C transporter is important for the excretion of rosuvastatin via the liver and intestine.

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.

Secondary prevention: for pre-existing cardiovascular disease or serious vascular event.

Primary prevention for ≥10% 10-year risk after SCORE/SCORE2 surgery for the prevention of atherosclerosis according to the applicable guidelines.

Familial hypercholesterolemia from 6 years starting dose 5mg; maximum dose 20mg.

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

Dosage according to guidelines (Mach F et al 2020) according to target value with lowest necessary dose; recommended starting dose for rosuvastatin 5mg/10mg according to LDL-C target value. if necessary, increase dose slowly at 4-6 week intervals;

Avoid high doses; if necessary, start combination therapy (ezetimibe) at an early stage; take individual patient factors into account.

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

Administration: orally as a tablet, once daily, independent of food.

Preferably taken in the evening; improved efficacy, as cholesterol synthesis depends on the time of day with highest cholesterol synthesis at night or early in the morning. As the HWZ is longer, it can also be taken at any other time of day.

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

For children (FH), observe the respective maximum dose for the age group (only data on this is available)! Treatment only by specialists! Starting dose 5 mg; low doses already have a strong effect in children! Increase only slowly at 4-6 week intervals.

Therapy adherence is important and should be discussed with patients!

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 rosuvastatin:

OATP1B1

• Carbamazepine, clarithromycin, ciclosporin, erythromycin, gemfibrozil, protease inhibitors (HIV), roxithromycin, sacubitril.

Generally lower risk for WW, however, as only low metabolism via the liver or Cyt P 450, but rosuvastatin is a substrate of various transport proteins (e.g. OATP1B1 and BCRP).

Do not use together with Ciclosporin! (contraindication!).

Certain protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir and/or tipranavir.

Do not use together with systemic fusidic acid (pause therapy for rosuvastatin until 7 days after the end of fusidic acid treatment).

Ticagrelor may affect renal excretion; increased risk of rosuvastatin accumulation; concomitant use of ticagrelor and rosuvastatin may lead to a decrease in renal function!

For further information and on substances that can be used with dose restrictions - see the Information for healthcare professionals.

Note: 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!

known hypersensitivity to rosuvastatin or one of its components;

active liver disease; unexplained and persistent elevation of serum transaminases; increase in serum transaminase concentration to ≥3 times the upper normal value

severe renal dysfunction (creatinine clearance < 30 ml/min);

Myopathy;

contraindicated for concomitant treatment with a combination of sofosbuvir/velpatasvir/voxilaprevir

contraindicated in concomitant treatment with ciclosporin;

during pregnancy and lactation and in women of childbearing age who are not using appropriate contraceptive measures.

The dose of 40 mg (maximum dose) is contraindicated in patients with predisposing factors for: myopathy/rhabdomyolysis;

moderate renal impairment (creatinine clearance < 60 ml/min);

hypothyroidism;

hereditary muscle diseases in personal or family history;

muscle-damaging effects due to previous intake of a fibrate

or another HMG-CoA reductase inhibitor;

alcohol abuse;

possibly increased plasma concentrations (e.g. Asian descent, simultaneous use of fibrates)

1. Information for healthcare professionals Crestor (rosuvastatin). Status August 2024; www.fachinfo.de/fi/pdf/011530/crestor-r-5-mg-10-mg-20-mg-filmtabletten
2. 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 https://doi.org/10.1093/eurheartj/ehz455