PRAVASTATINE GT

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 and exposed to a 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 or unstable angina and a normal or high cholesterol level, in addition to the correction of other risk factors (see section 5.1).

Post-transplantation

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

Pregnancy

Pravastatin is contraindicated during pregnancy and should be administered to women of childbearing age only if conception is unlikely and if these patients have been informed of the potential risk. Particular attention is recommended in adolescents of childbearing age to ensure their good understanding of the potential risk of pravastatin treatment during pregnancy. If a patient plans or declares a pregnancy, the doctor must be informed immediately and the administration of pravastatin must be stopped due to the potential risk to the fetus.

Breastfeeding

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

Pravastatine has no or little influence on the ability to drive vehicles or use machines. However, when driving vehicles or using machines, the possible occurrence of dizziness, visual disturbances, sleep disturbances (including insomnia and nightmares), memory loss and depression 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, < 1/1 000); very rare (< 1/10 000); not known: cannot be estimated from the available data.

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 were 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: vision disorders (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 CARE, WOSCOPS and 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 in 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 (> 3 N) 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 with long-term use, paraesthesia.

Not known: nightmares, memory loss, depression, myasthenia.

Eye disorders:

Not known: ocular myasthenia.

Immune system disorders:

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

Gastrointestinal disorders:

Very rare: pancreatitis.

Hepatobiliary disorders:

Very rare: jaundice, hepatitis, fulminant hepatic necrosis.

Unknown: fatal or non-fatal hepatic failure.

Skin and subcutaneous tissue disorders:

Rare: photosensitivity

Very rare: dermatomyositis

Frequency unknown: lichenoid eruption

Musculoskeletal and connective tissue disorders:

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

Isolated cases of tendon disorders, sometimes complicated by rupture.

Frequency not known: immune-mediated necrotizing myopathy (see section 4.4), muscle tear.

Respiratory, thoracic and mediastinal disorders:

Exceptional cases of interstitial lung disease, particularly during long-term therapy.

Metabolism and nutrition disorders:

Diabetes mellitus¹.

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

¹ derived from the review of the risk of diabetes by the European Pharmacovigilance Group.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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.