STANORM

Hypercholesterolemia

ATORVASTATINE ZYDUS 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 mixed hyperlipidemia (corresponding to types IIa and IIb of the Fredrickson classification), when response to diet or other non-pharmacological treatments is insufficient.

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

In controlled clinical studies comparing the effect of atorvastatin to a placebo in 16 066 patients (8 755 patients treated with atorvastatin versus 7 311 patients receiving a placebo) treated for a mean duration of 53 weeks, 5.2 % of patients treated with atorvastatin discontinued treatment due to adverse effects, compared to 4.0 % of patients receiving a placebo.

The adverse effects presented below are derived from clinical studies and the extensive experience acquired since the marketing of ATORVASTATINE ZYDUS.

The estimated frequencies of adverse effects are classified according to the following convention: common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000); unknown frequency (cannot be estimated on the basis of available data).

Infections and infestations

Common: nasopharyngitis.

Blood disorders and lymphatic system disorders

Rare: thrombocytopenia.

Immune system disorders

Common: allergic reactions.

Very rare: anaphylaxis.

Metabolism and nutrition disorders

Common: hyperglycaemia.

Uncommon: hypoglycaemia, weight increase, anorexia.

Psychiatric disorders

Uncommon: nightmares, insomnia.

Nervous system disorders

Common: headache.

Uncommon: dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia..

Rare: peripheral neuropathy.

Unknown frequency: myasthenia.

Eye disorders

Uncommon: blurred vision.

Rare: visual disorders.

Unknown frequency: ocular myasthenia.

Ear and labyrinth disorders

Uncommon: tinnitus.

Very rare: hearing loss.

Respiratory, thoracic and mediastinal disorders

Common: pharyngolaryngeal pain, epistaxis.

Gastrointestinal disorders

Common: constipation, flatulence, dyspepsia, nausea, diarrhoea.

Uncommon: vomiting, upper and lower abdominal pain, eructation, pancreatitis.

Hepatobiliary disorders

Uncommon: hepatitis.

Rare: cholestasis.

Very rare: hepatic insufficiency.

Vascular disorders

Rare: vasculitis.

Skin and subcutaneous tissue disorders

Uncommon: urticaria, skin rash, pruritus, alopecia.

Rare: angioedema, bullous dermatosis including erythema multiforme, Stevens-Johnson syndrome and Lyell syndrome, lichenoid reaction of drug origin.

Musculoskeletal and connective tissue disorders

Common: myalgia, arthralgia, pain in extremities, muscle spasms, joint swelling, back pain.

Uncommon: neck pain, muscular fatigue.

Rare: myopathy, myositis, rhabdomyolysis, muscle rupture, tendinopathy, sometimes complicated by a rupture.

Very rare: lupoid syndrome.

Unknown frequency: autoimmune mediated necrotizing myopathy (see section 4.4).

Reproductive system and breast disorders

Very rare: gynecomastia.

General disorders and administration site conditions

Uncommon: malaise, asthenia, chest pain, peripheral oedema, fatigue, pyrexia.

Investigations

Common: abnormal liver function tests, increase in blood creatine phosphokinase levels.

Uncommon: leucocyturia.

As with other HMG-CoA reductase inhibitors, increases in serum transaminase levels have been reported in patients receiving atorvastatine. These changes have usually been mild and transient and have not required discontinuation of treatment.

Clinically significant increases (> 3 times the upper limit of normal) in serum transaminase levels have been observed in 0,8 % of patients treated with atorvastatine. These increases were dose-dependent and reversible in all patients.

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

Pediatric population

Children aged 10 to 17 years treated with atorvastatine have a generally similar adverse effect profile to that of patients treated with placebo; the most frequently observed adverse effects 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, assessment according to Tanner classification and measurement of height and weight. The safety and tolerability profile in pediatric patients was similar to the known safety profile of atorvastatine in adult patients.

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

The following adverse events have been reported with certain 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, increase in triglyceride levels, history of hypertension).

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 Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/ .