TAHOR

Hypercholesterolemia

ATORVASTATINE EVOLUGEN is indicated as an adjunct to a diet to reduce elevated levels of total cholesterol (Chol-T), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents, and children aged 10 years or older with primary hypercholesterolemia including familial (heterozygous) hypercholesterolemia or combined (mixed) hyperlipidemias (corresponding to types IIa and IIb of the Fredrickson classification), when response to diet or other non-pharmacological treatments is insufficient.

ATORVASTATINE EVOLUGEN is also indicated to reduce levels of Chol-T and LDL-C in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (notably LDL apheresis) or if such treatments are unavailable.

Prevention of cardiovascular diseases

Prevention of cardiovascular events in adult patients at high risk of presenting a first cardiovascular event (see section 5.1), as an adjunct to the correction of other risk factors

ATORVASTATINE EVOLUGEN has only a negligible effect on the ability to drive and use machines.

In controlled clinical studies comparing the effect of atorvastatin to a placebo in 16 066 patients (8755 patients treated with atorvastatin versus 7311 patients receiving a placebo) treated for a mean duration of 53 weeks, 5,2 % of patients treated with atorvastatin discontinued treatment due to adverse reactions, compared to 4,0 % of patients receiving a placebo.

The adverse reactions presented below observed with atorvastatin are derived from clinical studies and extensive post-marketing experience with atorvastatin.

The estimated frequencies of adverse reactions are ranked according to the following convention: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1 000); very rare (< 1/10000); not known (cannot be estimated from the available data).

As with other HMG-CoA reductase inhibitors, increases in serum transaminase levels have been reported in patients receiving atorvastatin. These changes were usually mild and transient and did not require interruption of treatment. Clinically significant increases (> 3 times the ULN) in serum transaminase levels were observed in 0,8 % of patients treated with atorvastatin. These increases were dose-related and reversible in all patients.

An increase in serum creatine phosphokinase (CPK) levels of more than three times the ULN was observed in 2,5 % of patients taking atorvastatin, a proportion similar to that observed with other HMG-CoA reductase inhibitors during clinical studies. Serum levels greater than ten times the ULN were noted in 0,4 % of patients treated with atorvastatin (see section 4.4).

Pediatric population

Children aged 10 to 17 years treated with atorvastatin have an adverse event profile generally similar to that of patients treated with placebo; the most frequently observed adverse events in both groups were infections, regardless of causality assessment. No clinically significant effect on growth and sexual maturation was observed during a 3-year study based on the assessment of overall maturation and development, Tanner stage assessment, and measurement of height and weight. The safety and tolerability profile in pediatric patients was similar to the known safety profile of atorvastatin in adult patients.

The clinical pharmacovigilance database includes safety data for 520 pediatric patients who received atorvastatin, among whom 7 patients were aged less than 6 years, 121 patients were in an age range of 6 to 9 years, and 392 patients were in an age range of 10 to 17 years. Based on the available data, the frequency, type, and severity of adverse reactions are similar in children and adults.

The following adverse events have been reported with some statins:

· Sexual disorders.

· Depression.

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

· Diabetes: The frequency depends on the presence or absence of risk factors (fasting blood glucose ≥ 5,6 mmol/l, BMI > 30 kg/m², increased triglyceride levels, history of arterial hypertension).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction 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/