Package leaflet: Information for the patient

APLACTIN 20 mg tablets, 40 mg tablets

sodium pravastatin
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, because it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What APLACTIN is and what it is used for
What you need to know before taking APLACTIN
How to take APLACTIN
Possible side effects
How to store APLACTIN
Contents of the pack and other information

1. What APLACTIN is and what it is used for

APLACTIN contains pravastatin, a substance belonging to the group of statins, medicines that reduce blood levels of fats and cholesterol. This effect is achieved by inhibiting a key enzyme involved in cholesterol synthesis, called HMG-CoA reductase.
APLACTIN is indicated in adults in the following cases:

Hypercholesterolemia (excess cholesterol in the blood): Treatment of primary hypercholesterolemia (familial) or mixed dyslipidemia (abnormal blood fat levels), as an adjunct to diet, when response to diet or other non-pharmacological interventions (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 with a history of 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-transplant: Reduction of hyperlipidemia (increased blood fat levels) following organ transplantation in patients receiving immunosuppressive therapy (treatment to prevent organ rejection) after solid organ transplantation (e.g., liver, pancreas, kidneys) (see section 3 “How to take APLACTIN” and “Other medicines and APLACTIN”).

2. What you need to know before taking APLACTIN

Do not take APLACTIN

If you are allergic to pravastatin or 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 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 APLACTIN.
Your doctor will perform a blood test before you start taking APLACTIN and if you develop symptoms of liver problems while taking APLACTIN, to monitor liver function.
Your doctor may also request further blood tests to check liver function after you have started taking APLACTIN.
The risk of muscle problems is higher in certain patients. Inform your doctor if any of the following apply:

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 APLACTIN") or another cholesterol-lowering medicine such as nicotinic acid (niacin);
if you or someone in your family has hereditary muscle disorders;
if you are an alcoholic (alcohol dependence);
if you are over 70 years old, especially if you have other risk factors for muscle disorders;
if you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (used to treat bacterial infections); combining fusidic acid with APLACTIN can cause serious 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 occasionally 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 pain, stiffness, weakness or unexplained muscle cramps, as blood tests to evaluate creatine kinase (CK) levels may be required or treatment discontinuation may be necessary.
This medicine can cause muscle problems such as myalgia (muscle pain) and myopathy (muscle disease). Very rarely, rhabdomyolysis (a condition characterized by damage to muscle fibres), 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 tests and treatments may be needed 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 problem) may occur:

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

During treatment with this medicine, your doctor will monitor liver enzyme levels (AST and ALT) and will instruct you to stop treatment with APLACTIN if levels exceed three times the normal values persistently. Inform your doctor if you have previously suffered from liver disease (hepatopathy) or if you regularly consume alcohol, as particular caution is required in these cases.
During treatment with this medicine, blood glucose levels (sugar concentration in the blood) may rise and, in some patients at high risk of developing diabetes, may lead to excessive blood sugar (hyperglycaemia), requiring antidiabetic therapy.
Your doctor will closely monitor you if you have high blood glucose, triglyceride (fat) levels and high blood pressure.
APLACTIN is not suitable when hypercholesterolaemia is due to high HDL cholesterol levels.
Children and adolescents
The use of APLACTIN in patients under 18 years of age is not recommended.
Other medicines and APLACTIN
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 APLACTIN is not recommended as it may increase the risk of muscle 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 APLACTIN is taken at the same time as these medicines, its therapeutic effect may be reduced. APLACTIN should be taken 1 hour before or 4 hours after cholestyramine, or 1 hour before colestipol, to avoid reduced efficacy of pravastatin (see section 3 “How to take APLACTIN”);
Cyclosporine. Concomitant use of cyclosporine (a medicine used to prevent organ transplant rejection) and APLACTIN increases systemic exposure to the drug 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 APLACTIN, because concomitant use of vitamin K antagonists with APLACTIN may alter blood test results used to monitor vitamin K antagonist therapy.
Taking APLACTIN with any of these medicines may increase the risk of muscle 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 resume treatment with APLACTIN. Taking APLACTIN 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 APLACTIN during pregnancy (see "Do not take APLACTIN"). If you become pregnant or are planning a pregnancy while taking APLACTIN, inform your doctor immediately and stop treatment due to the potential risk to the fetus.
Breastfeeding
Do not take APLACTIN while breastfeeding, as small amounts of pravastatin are excreted in breast milk (see "Do not take APLACTIN").
Driving and using machines
APLACTIN does not affect or has negligible effect on the ability to drive or use machines.
However, dizziness may occur after taking APLACTIN. If this occurs, avoid driving or using machines.
APLACTIN contains lactose and sodium.
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him 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 APLACTIN

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
Before starting treatment with APLACTIN, your doctor will rule out secondary causes of hypercholesterolemia (e.g. hypothyroidism, diabetes mellitus, excessive dietary fat intake).
Before and during treatment with APLACTIN, you must follow a diet aimed at reducing blood lipid levels (standard lipid-lowering diet).
Take APLACTIN 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:

For the treatment of hypercholesterolemia (elevated blood lipid 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 lipid levels and adjust the dose accordingly. The maximum daily dose is 40 mg.
For cardiovascular prevention (prevention of heart disorders): 40 mg daily.
For 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 APLACTIN is not recommended.
Use in the elderly
Dose adjustment is not required in elderly patients 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 lipid levels.
Concomitant therapy with other medicines
If you are taking a resin (i.e. a bile acid sequestrant such as cholestyramine or colestipol), take APLACTIN at least one hour before or at least four hours after the resin (see "Other medicines and APLACTIN").
If you are taking cyclosporine (a medicine used in organ transplantation), with or without other immunosuppressants, the recommended starting dose of APLACTIN is 20 mg daily.
Dose increases up to 40 mg should be performed cautiously and under medical supervision (see "Other medicines and APLACTIN").
If you take more APLACTIN than you should
In case of accidental ingestion or overdose of APLACTIN, 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 side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Most significant side 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 APLACTIN, the following additional side effects have also been reported:
Uncommon side 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, 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 side 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 (inflammation of the liver), and fulminant hepatic necrosis;
rhabdomyolysis (a condition characterized by injury 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 side effects

tendon disorders, sometimes complicated by rupture.

Side effects of 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 arm or leg weakness that worsens after periods of activity, double vision or drooping eyelids, difficulty swallowing, or shortness of breath.
Side 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 rare cases, especially during 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 muscles and skin).

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

5. How to store APLACTIN

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,
correctly 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 APLACTIN contains
APLACTIN 20 mg tablets
Each 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)).
APLACTIN 40 mg tablets
Each 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 APLACTIN and contents of the pack
APLACTIN 20 mg tablets
Available in packs of 10 and 28 tablets of 20 mg
APLACTIN 40 mg tablets
Available in packs of 14 and 28 tablets of 40 mg
Marketing Authorization Holder
F.I.R.M.A. S.p.A., Via di Scandicci 37 - Florence
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.