Prasterol

Package leaflet: Information for the patient

PRASTEROL 20 mg tablets, 40 mg tablets

pravastatin sodium
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What PRASTEROL is and what it is used for
2. What you need to know before taking PRASTEROL
3. How to take PRASTEROL
4. Possible side effects
5. How to store PRASTEROL
6. Contents of the pack and other information

1. What PRASTEROL is and what it is used for

PRASTEROL contains pravastatin, a substance belonging to the group of statins, medicines that are able to reduce the levels of fats and cholesterol in the blood. This effect is achieved by inhibiting an enzyme important in cholesterol synthesis, known as HMG-CoA reductase.
PRASTEROL is indicated in adults in the following cases:

• Hypercholesterolemia (excess cholesterol in the blood) Treatment of primary hypercholesterolemia (familial) or mixed dyslipidemia (abnormal levels of fats in the blood), as an adjunct to diet, when response to diet or other non-pharmacological treatments (e.g. exercise or weight reduction) has been inadequate.

• Primary prevention Reduction of mortality and incidence of cardiovascular diseases (affecting the heart and/or blood vessels) in patients with moderate to severe hypercholesterolemia and at high risk of a first cardiovascular event (e.g. heart attack, stroke), as an adjunct to diet.

• Secondary prevention Reduction of mortality and incidence of cardiovascular diseases in patients who have previously experienced myocardial infarction (death of a portion of heart tissue due to blockage of a blood vessel supplying the heart) or unstable angina pectoris (chest pain due to a temporary reduction in blood and oxygen supply to the heart), and who have normal or elevated cholesterol levels, in addition to correction of other risk factors.

• Post-transplantation Reduction of hyperlipidemia (increased levels of fats in the blood) following organ transplantation in patients undergoing immunosuppressive therapy (treatment to prevent organ rejection) after solid organ transplantation (e.g. liver, pancreas, kidneys) (see section 3 “How to take PRASTEROL” and “Other medicines and PRASTEROL”).

2. What you need to know before taking PRASTEROL

Do not take PRASTEROL

• If you are allergic to pravastatin or to any of the other ingredients of this medicine (listed in section 6).
• If you have active liver disease or if you have a marked and persistent increase in blood transaminase levels (liver function enzymes) exceeding three times the upper normal limit (see "Warnings and precautions").
• If you are pregnant or breastfeeding (see "Pregnancy and Breastfeeding").

Warnings and precautions
Talk to your doctor or pharmacist before taking PRASTEROL.
Your doctor will arrange for a blood test before you start taking PRASTEROL and if you develop symptoms of liver problems while taking PRASTEROL. This is to monitor liver function.
Your doctor may also request further blood tests to monitor liver function after you have started taking PRASTEROL.
The risk of muscle-related problems is higher in certain patients. Inform your doctor if any of the following apply to you:

• if you have renal insufficiency (impaired kidney function);
• if you have hypothyroidism (reduced thyroid function);
• if you have previously experienced muscle toxicity while taking statins or fibrates (see "Other medicines and PRASTEROL") or another cholesterol-lowering medicine such as nicotinic acid (niacin);
• if you or a family member has a hereditary muscle disorder;
• if you suffer from alcoholism (alcohol dependence);
• if you are over 70 years of age, especially if you have other risk factors for muscle disorders;
• if you are currently taking or have taken within the last 7 days a medicine called fusidic acid (used to treat bacterial infections) orally or by injection; the combination of fusidic acid with PRASTEROL may cause severe muscle problems (rhabdomyolysis);
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), since statins may sometimes worsen myasthenia or trigger its onset (see section 4).

In these cases, your doctor should perform a blood test to assess creatine kinase (CK) levels before starting treatment.
Inform your doctor immediately if, during treatment, you experience symptoms such as unexplained muscle pain, tenderness, weakness, or cramps, as blood tests to evaluate creatine kinase (CK) levels may be needed, or treatment may need to be discontinued.
This medicine may cause muscle problems such as myalgia (muscle pain), myopathy (muscle disease). Very rarely, rhabdomyolysis (a condition characterized by damage to muscle fibers), which may be fatal, can occur and may be associated with secondary renal failure (impaired kidney function due to other conditions).
Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further investigations and treatment may be required to diagnose and manage this condition.
Stop treatment with this medicine and consult your doctor if you experience any of the following symptoms, especially if you are on long-term treatment, as interstitial lung disease (a lung condition) may occur:

• dyspnea (difficulty breathing);
• dry cough;
• fatigue;
• weight loss and fever.

During treatment with this medicine, your doctor will monitor your liver enzyme levels (AST and ALT) and will instruct you to stop taking PRASTEROL if levels exceed three times the normal upper limit consistently. Inform your doctor if you have previously suffered from liver disease (hepatopathy) or if you regularly consume alcohol, as extra caution is required in these cases.
During treatment with this medicine, blood glucose levels may increase and, in some patients at high risk of developing diabetes, may lead to excessive blood sugar (hyperglycemia), possibly requiring antidiabetic therapy.
Your doctor will closely monitor you if you have high blood glucose, triglyceride (fat) levels, and high blood pressure.
PRASTEROL is not suitable when hypercholesterolemia is due to high HDL cholesterol levels.
Children and adolescents
The use of PRASTEROL in patients under 18 years of age is not recommended.
Other medicines and PRASTEROL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor if you are taking medicines called fibrates (e.g. gemfibrozil, fenofibrate) used to lower blood fat (cholesterol) levels; concomitant use with PRASTEROL is not recommended as it may increase the risk of muscle-related problems (see "Warnings and precautions"). Your doctor will perform specific tests (monitoring creatine kinase, CK levels).
Take this medicine with caution and consult your doctor if you are taking the following medicines:

• Cholestyramine or Colestipol (medicines used to reduce cholesterol levels in the blood)

When PRASTEROL is taken at the same time as these medicines, its therapeutic effect may be reduced. PRASTEROL should be taken 1 hour before or 4 hours after cholestyramine, or 1 hour before colestipol, to avoid a reduction in pravastatin's therapeutic effect (see section 3 “How to take PRASTEROL”);

• Cyclosporine. Taking cyclosporine (a medicine used to prevent organ transplant rejection) together with PRASTEROL increases exposure to pravastatin by about 4 times or more;
• Erythromycin and clarithromycin (antibiotics). These medicines may increase the concentration of pravastatin in the blood.

If you are taking a medicine used to treat and prevent blood clots known as a "vitamin K antagonist", inform your doctor before taking PRASTEROL, as using vitamin K antagonists together with PRASTEROL may alter the results of blood tests used to monitor treatment with vitamin K antagonists.
Taking PRASTEROL with any of the following medicines may increase the risk of muscle-related problems:

• If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when you can restart PRASTEROL treatment. Taking PRASTEROL with fusidic acid may rarely cause muscle weakness, burning, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4 “Possible side effects”.
• Colchicine (used, for example, to treat gout)
• Rifampicin (used, for example, to treat an infection called tuberculosis)
• Lenalidomide (used, for example, to treat a type of blood cancer called multiple myeloma)

Pregnancy, breastfeeding, and fertility
Pregnancy
Do not take PRASTEROL during pregnancy (see “Do not take PRASTEROL”). If you become pregnant or are planning a pregnancy while taking PRASTEROL, inform your doctor immediately and stop treatment due to the potential risk to the fetus.
Breastfeeding
Do not take PRASTEROL while breastfeeding, as a small amount of pravastatin is excreted in breast milk (see “Do not take PRASTEROL”).
Driving and using machines
PRASTEROL does not affect or has a negligible effect on the ability to drive or operate machinery. However, dizziness may occur after taking PRASTEROL. If this happens, avoid driving or operating machinery.
PRASTEROL contains lactose and sodium.
This medicine contains lactose. If you have been diagnosed by your doctor with an intolerance to certain sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take PRASTEROL

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment with PRASTEROL, your doctor will rule out secondary causes of hypercholesterolemia (e.g. hypothyroidism, diabetes mellitus, excessive dietary fat intake).
Before and during treatment with PRASTEROL, you must follow a diet aimed at reducing blood fat levels (standard lipid-lowering diet).
Take PRASTEROL orally once daily, preferably in the evening, with or without food.
The duration of treatment varies according to medical prescription.
The recommended dose varies in the following cases:

• in the treatment of hypercholesterolemia (elevated blood fat levels): 10–40 mg once daily. A response is observed within one week, and maximum effect is achieved within four weeks. Your doctor will monitor your blood fat levels and adjust the dose accordingly. The maximum daily dose is 40 mg.
• in cardiovascular prevention (prevention of heart disorders): 40 mg daily.
• in therapy after organ transplantation: the recommended starting dose is 20 mg daily if you are receiving specific medications (immunosuppressive therapy). Your doctor will adjust the dose up to a maximum of 40 mg daily.

Use in children and adolescents
The use of PRASTEROL is not recommended.
Use in the elderly
In elderly patients, dose adjustment is not normally required unless risk factors are present (see "Warnings and precautions").
Use in patients with renal or hepatic impairment (kidney or liver problems)
If you have moderate or severe renal impairment or significant hepatic impairment, the recommended starting dose is 10 mg daily. Your doctor will adjust the dose based on blood fat levels.
Concomitant therapy with other medicines
If you are taking a resin, i.e. a bile acid sequestrant (such as colestyramine or colestipol), take PRASTEROL at least one hour before or at least four hours after the resin (see "Other medicines and PRASTEROL").
If you are taking cyclosporine (a medicine used in organ transplantation), with or without other immunosuppressants, the recommended starting dose of PRASTEROL is 20 mg daily. Any dose increase up to 40 mg should be done cautiously and under medical supervision (see "Other medicines and PRASTEROL").
If you take more PRASTEROL than you should
In case of accidental ingestion/overdose of PRASTEROL, contact your doctor immediately or go to the nearest hospital.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
More significant adverse effects:

• muscle pain (myalgia), joint pain (arthralgia), muscle cramps, muscle weakness, elevated levels of a substance produced by muscles (creatine kinase, CK);
• increased levels of liver enzymes (serum transaminases).

During clinical studies and following the marketing of PRASTEROL, the following adverse effects have also been reported:
Uncommon adverse effects (may affect up to 1 in 100 patients)

• dizziness, headache (cephalalgia);
• sleep disorders, including insomnia and nightmares;
• visual disturbances, including blurred vision and double vision;
• digestive disturbances and heartburn, abdominal pain, nausea, vomiting, constipation, diarrhoea, bloating;
• itching, skin rash, urticaria, scalp and hair disorders, including hair loss;
• difficulty urinating (dysuria), frequent passage of small amounts of urine (pollakiuria), and repeated need to urinate during the night (nocturia);
• sexual dysfunction;
• fatigue.

Very rare adverse effects (may affect up to 1 in 10,000 patients)

• peripheral polyneuropathy (a disease affecting multiple nerves), especially with prolonged treatment, and paresthesia (reduced sensation in part of the body);
• hypersensitivity reactions such as anaphylaxis, angioedema, lupus erythematosus-like syndrome;
• pancreatitis (inflammation of the pancreas);
• jaundice (yellowing of the skin), hepatitis (liver inflammation), and fulminant hepatic necrosis;
• rhabdomyolysis (a condition characterized by damage to muscle fibres) which may be associated with acute renal failure secondary to myoglobinuria (presence of myoglobin in urine) and myopathy (muscle disorders) (see "Warnings and precautions");
• liver failure.

Isolated adverse effects

• tendon disorders, sometimes complicated by rupture.

Adverse effects with unknown frequency (frequency cannot be estimated from the available data)

• persistent muscle weakness (immune-mediated necrotizing myopathy);
• myasthenia gravis (a disease causing generalized muscle weakness, including in some cases the muscles used for breathing);
• ocular myasthenia (a disease causing weakness of the eye muscles).

Contact your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or shortness of breath.
Adverse effects related to the statin class

• nightmares;
• memory loss;
• depression;
• interstitial lung disease (a condition characterized by changes in the tissue lining the lung alveoli, which may present with breathing problems such as persistent cough and/or shortness of breath), in exceptional cases especially with long-term therapy (see "Warnings and precautions");
• type 2 diabetes mellitus: frequency depends on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI > 30 kg/m², elevated triglyceride levels, history of hypertension);
• dermatomyositis (a condition characterized by inflammation of the muscles and skin).

Following the instructions contained in this leaflet reduces the risk of adverse effects.
Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store PRASTEROL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp".
The expiry date refers to the last day of that month and to the product in its original sealed packaging,
properly stored.
Store the medicine below 30 °C.
Keep in the original packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PRASTEROL contains
PRASTEROL 20 mg tablets
One 20 mg tablet contains:
The active substance is pravastatin sodium 20 mg.
The other components are monohydrate lactose, polyvinylpyrrolidone, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, magnesium oxide, yellow colouring mixture (microcrystalline cellulose and yellow iron oxide (E172)).
PRASTEROL 40 mg tablets
One 40 mg tablet contains:
The active substance is pravastatin sodium 40 mg.
The other components are monohydrate lactose, polyvinylpyrrolidone, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, magnesium oxide, yellow colouring mixture (microcrystalline cellulose and yellow iron oxide (E172)).

Description of the appearance of PRASTEROL and pack sizes
PRASTEROL 20 mg tablets
Available in packs of 10 and 28 tablets of 20 mg.
PRASTEROL 40 mg tablets
Available in packs of 14 and 28 tablets of 40 mg.

Marketing Authorization Holder
Istituto Luso Farmaco d'Italia S.p.A.
Milanofiori – Strada 6 – Edificio L – Rozzano (MI)

Manufacturer
A. Menarini Manufacturing Logistics and Services s.r.l., Campo di Pile, L'Aquila.
Menarini von Heyden GmbH Leipziger Straße 7 D-01097 Dresden.