PRASTENOR

Hypercholesterolemia

Treatment of primary hypercholesterolemia or mixed dyslipidemias, as an adjunct to a diet, when response to diet and other non-pharmacological treatments (for example, exercise, weight loss) is insufficient.

Primary prevention

Reduction of cardiovascular mortality and morbidity in patients with moderate or severe hypercholesterolemia at high risk of a first cardiovascular event, as an adjunct to a diet (see section 5.1).

Secondary prevention

Reduction of cardiovascular mortality and morbidity in patients with a history of myocardial infarction (MI) or unstable angina and normal or high cholesterol levels, in addition to correction of other risk factors (see section 5.1).

Post-transplantation

Reduction of post-transplantation hyperlipidemia in patients receiving immunosuppressive treatment following organ transplantation (see sections 4.2, 4.5 and 5.1).

Pregnancy

Pravastatin is contraindicated during pregnancy and should be administered to women of childbearing potential only if conception is unlikely and if these patients have been informed of the potential risk. Particular attention is recommended in adolescent females of childbearing potential to ensure their good understanding of the potential risk of pravastatin treatment during pregnancy. If a patient plans or declares a pregnancy, the physician must be informed immediately and pravastatin administration must be discontinued due to the potential risk to the fetus (see section 4.3).

Breastfeeding

A small amount of pravastatin is excreted in breast milk. Consequently, pravastatin administration during breastfeeding is contraindicated (see section 4.3).

Pravastatin has no effect or a negligible effect on the ability to drive vehicles or use machines. However, when driving vehicles or using machines, the possible occurrence of dizziness and visual disturbances during treatment should be taken into account.

The frequencies of adverse events are classified as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1000); very rare (< 1/10 000), frequency not known (cannot be estimated from the available data). Within each frequency group, adverse effects are presented in order of decreasing seriousness.

Clinical trials: pravastatin was studied at a dose of 40 mg in seven randomized, double-blind, placebo-controlled studies involving more than 21 000 patients treated with pravastatin (N=10 764) or placebo (N=10 719), representing more than 47 000 patient-years of exposure to pravastatin. More than 19 000 patients were followed for a median duration of 4,8 to 5,9 years.

The following adverse events have been reported, none of them was observed at a frequency greater than 0,3% in the group treated with pravastatin, compared to the placebo group.

Nervous system disorders:

Uncommon: dizziness, headache, sleep disturbances, insomnia.

Eye disorders:

Uncommon: visual disturbances (including blurred vision and diplopia).

Gastrointestinal disorders:

Uncommon: dyspepsia/heartburn, abdominal pain, nausea/vomiting, constipation, diarrhea, flatulence.

Skin and subcutaneous tissue disorders:

Uncommon: pruritus, rash, urticaria, scalp and hair abnormalities (including alopecia).

Renal and urinary disorders:

Uncommon: abnormal micturition (including dysuria, frequency, nocturia).

Reproductive system and breast disorders:

Uncommon: sexual dysfunction.

General disorders:

Uncommon: fatigue.

Events of particular clinical interest

Skeletal muscles:

Effects on skeletal muscles, e.g., musculoskeletal pain, including arthralgia, muscle cramps, myalgia, muscle weakness and elevated CPK levels have been reported in clinical studies. In the Cholesterol and Recurrent Events (CARE), West of Scotland Coronary Prevention Study (WOSCOPS) and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies, the percentage of myalgia (1.4% on pravastatin vs 1.4% on placebo), muscle weakness (0.1% on pravastatin vs < 0.1% on placebo) and the incidence of CPK levels > 3 N and > 10 N (1.6% on pravastatin vs 1.6% on placebo and 1.0% on pravastatin vs 1.0% on placebo, respectively) was similar to placebo (see section 4.4).

Hepatic effects:

Elevations of serum transaminases have been reported. In the three long-term, placebo-controlled studies, CARE, WOSCOPS and LIPID, the frequency of marked abnormalities in ALAT and ASAT levels (> 3N) was similar in both treatment groups (≤1.2%).

Post-marketing experience

In addition to the events listed above, the following adverse events have been reported since the marketing of pravastatin:

Nervous system disorders:

Very rare: peripheral polyneuropathy, especially in case of prolonged use, paraesthesia.

Not known: myasthenia.

Eye disorders:

Not known: ocular myasthenia.

Immune system disorders:

Very rare: hypersensitivity reactions: anaphylaxis, angioedema, lupus erythematosus-like syndrome.

Gastrointestinal disorders:

Very rare: pancreatitis.

Hepatobiliary disorders:

Very rare: jaundice, hepatitis, fulminant hepatic necrosis.

Not known: fatal or non-fatal hepatic failure.

Musculoskeletal and systemic disorders:

Very rare: rhabdomyolysis, which may be associated with acute renal failure secondary to myoglobinuria, myopathy (see section 4.4), myositis, polymyositis.

Uncommon: tendon disorders, especially tendonitis, sometimes complicated by rupture.

Not known: immune-mediated necrotizing myopathy (see section 4.4), muscle strains, tears and ruptures.

Skin and subcutaneous tissue disorders:

Rare: photosensitivity.

Very rare: dermatomyositis.

Not known: skin rash, including lichenoid rash.

The following adverse effects have been reported with the statin class:

· Nightmares.

· Memory loss.

· Depression.

· Exceptional cases of interstitial lung disease, especially in long-term treatments (see section 4.4),

· Diabetes mellitus: the frequency depends on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/l, BMI > 30 kg/m², increased triglycerides, history of arterial hypertension).

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/.