ROSUVAS SUN

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 (notably 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.

Pregnancy

ROSUVASTATINE BGR is contraindicated during pregnancy and breastfeeding.

Women of childbearing potential must use appropriate contraceptive measures.

As cholesterol and its derivatives are essential for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the expected benefit of statin treatment during pregnancy. Animal studies show limited reproductive toxicity (see section 5.3).

In the event of pregnancy during treatment, the treatment must be discontinued immediately.

Breastfeeding

Limited data from published reports indicate that rosuvastatin is present in human milk. In rats, rosuvastatin is excreted in milk. Due to the mechanism of action of ROSUVASTATINE BGR, there is a potential risk of adverse effects in the infant. ROSUVASTATINE BGR is contraindicated during breastfeeding.

Fertility

There are no known effects on fertility after the use of rosuvastatin.

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 patients treated with rosuvastatin had to discontinue treatment due to adverse effects.

Table of adverse effects

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

The frequencies of adverse effects are classified according to the following convention:

Common (≥ 1/100 - < 1/10), Uncommon (≥ 1/1000 - < 1/100), Rare (≥ 1/10 000 - < 1/1000), Very rare (<1/10 000), Unspecified frequency (frequency that cannot be estimated based on available data).

Table 2. Adverse effects identified during clinical trials and after marketing

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

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

Renal effects

A proteinuria, detected by urine strip and mainly of tubular origin, has been observed in patients treated with rosuvastatin. Changes in urinary proteins from absence or traces 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 changes from absence or traces to + was observed with the dose of 20 mg.

In most cases, proteinuria decreases or disappears spontaneously while treatment is continued. The review of data from clinical trials and experience since marketing has not identified a causal link between proteinuria and an acute or progressive renal condition.

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

Muscular effects

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

A dose-dependent increase in CPK has been observed in patients taking rosuvastatine; the majority of cases were benign, asymptomatic and transient.

If CPK levels are high (greater than 5 times the normal), treatment must be interrupted (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 benign, asymptomatic and transient.

The following adverse effects have been reported with some statins:

· sexual disorders

· exceptional cases of interstitial lung disease, particularly during long-term treatment (see section 4.4)

The rate of notification of rhabdomyolysis, serious renal events and serious hepatic events (consisting mainly of an increase in hepatic transaminases) since marketing is higher at the dose of 40 mg.

Pediatric population

Elevations of creatine kinase > 10 times the ULN (upper limit of normal) as well as muscular symptoms after increased physical activity have been observed more frequently in a 52-week clinical study in children and adolescents compared to adults (see section 4.4).

For other aspects, the tolerability 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 medicinal product authorisation is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Centres Régionaux de Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/ .