SUVAS IBERMA

Treatment of hypercholesterolemia

Adults, adolescents and children aged 6 years or older with pure hypercholesterolemia (type IIa including heterozygous familial hypercholesterolemia) or mixed dyslipidaemia (type IIb) as an adjunct to a diet when response to diet and other non-pharmacological treatments (exercise, weight loss) is insufficient.

Adults, adolescents and children aged 6 years or older with homozygous familial hypercholesterolemia, as an adjunct to a diet and other lipid-lowering treatments (for example LDL apheresis) or when these treatments are not appropriate.

Prevention of cardiovascular events

Prevention of major cardiovascular events in patients estimated to be at high risk of experiencing a first cardiovascular event (see section 5.1), as an adjunct to the correction of other risk factors.

Rosuvastatin is contraindicated during pregnancy and breastfeeding.

Women of childbearing potential should use adequate contraception measures.

As cholesterol and its derivatives are essential for fetal development, the potential risk of HMG-CoA réductase inhibition outweighs the expected benefit of statin treatment during pregnancy. Animal studies show limited reproductive toxicity (see section 5.3). If pregnancy is discovered during treatment, it must be discontinued immediately.

In rats, rosuvastatin is excreted in milk. In humans, there is no data concerning the passage of rosuvastatin into breast milk (see section 4.3).

No study has been conducted to determine the effect of rosuvastatin on the ability to use or drive vehicles. However, based on the pharmacodynamic properties of rosuvastatin, no effect is expected. When using a vehicle or operating machinery, the possible occurrence of dizziness must be taken into account.

The adverse effects observed with rosuvastatin are generally mild and transient. In controlled clinical trials, less than 4% of rosuvastatin-treated patients were withdrawn from therapy due to adverse effects.

Table of adverse effects

The table below presents the adverse effects of rosuvastatin, identified during clinical trials and post-marketing. The adverse effects listed below are classified according to their frequency and system organ class.

Frequencies of adverse effects are ranked according to the following convention: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (frequency cannot be estimated from the available data).

Table 2. Adverse effects identified during clinical trials and post-marketing

1: The frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI > 30 kg/m², elevated triglycerides, history of hypertension).

As with other HMG-CoA reductase inhibitors, the incidence of adverse events tends to be dose-dependent.

Renal effects

Proteinuria, detected by urine dipstick and mainly tubular in origin, has been observed in patients treated with rosuvastatin. Changes in urine protein from none or trace to ++ or more were observed in less than 1% of patients treated with 10 mg and 20 mg, and in approximately 3% of patients treated with 40 mg. A minor increase in change from none or trace to + was observed with the 20 mg dose.

In most cases, proteinuria decreases or disappears spontaneously while treatment is continued. Review of data from clinical trials and post-marketing experience has not identified a causal link between proteinuria and acute or progressive renal disease.

Hematuria has been observed in patients treated with rosuvastatine and clinical trial data show that the frequency of occurrence is low.

Muscular effects

Muscular effects such as myalgia, myopathy (including myositis) and rarely rhabdomyolysis with or without acute renal failure have been observed in patients treated with rosuvastatine, at all doses and in particular at doses > 20 mg.

A dose-dependent increase in CPK has been observed in patients taking rosuvastatine; the majority of cases were mild, asymptomatic and transient. If CPK levels are elevated (greater than 5 times the upper limit of normal), treatment should be discontinued (see section 4.4).

Hepatic effects

As with other HMG-CoA reductase inhibitors, a dose-dependent increase in transaminases has been reported in a small number of patients treated with rosuvastatine. The majority of reported cases were mild, asymptomatic and transient.

The following adverse effects have been reported with some statins:

· Sexual disorders.

· Exceptional cases of interstitial lung disease, in particular during long-term treatment (see section 4.4).

The reporting rate for rhabdomyolysis, serious renal events and serious hepatic events (consisting mainly of increased hepatic transaminases) is higher at the 40 mg dose.

Pediatric population

Elevations of creatine kinase > 10 times the ULN (upper limit of normal) as well as muscular symptoms after increased physical activity were observed more frequently in a 52-week clinical study in children and adolescents compared to adults (see section 4.4). For other aspects, the safety profile of rosuvastatine was similar in children and adolescents compared to that of adults.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization of the medicine is important. It allows continuous monitoring of the benefit/risk ratio of the medicine. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/ .