Apo-simva 20

Patient Information Leaflet

Apo-Simva 10, 10 mg, film-coated tablets
Apo-Simva 20, 20 mg, film-coated tablets
Apo-Simva 40, 40 mg, film-coated tablets
Simvastatin

Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are similar.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents:

1. What Apo-Simva is and what it is used for
2. Important information before taking Apo-Simva
3. How to take Apo-Simva
4. Possible side effects
5. How to store Apo-Simva
6. Contents of the pack and other information

1. What Apo-Simva is and what it is used for

Apo-Simva contains the active substance simvastatin. Apo-Simva belongs to a group of medicines called statins. Apo-Simva is used to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. Additionally, Apo-Simva increases levels of "good" cholesterol (HDL cholesterol).

Cholesterol is one of several fatty substances present in the blood. Total cholesterol consists mainly of LDL cholesterol and HDL cholesterol fractions.

LDL cholesterol is often called "bad" cholesterol because it can deposit on the walls of arteries, forming atherosclerotic plaques. Eventually, these plaques can narrow the arteries, restricting or blocking blood flow to vital organs such as the heart and brain. Blocked blood flow may lead to heart attack or stroke.

HDL cholesterol is often called "good" cholesterol because it helps prevent the buildup of bad cholesterol in the arteries and protects against heart disease.

Triglycerides are another type of fat in the blood that may contribute to an increased risk of heart disease.

While taking this medicine, you should follow a cholesterol-lowering diet. Apo-Simva is used as an adjunct to a cholesterol-lowering diet:

• to reduce cholesterol and triglyceride levels in the blood when response to diet and other treatment methods (such as physical exercise, weight reduction) is inadequate;
• to reduce inherited high blood cholesterol levels (familial homozygous hypercholesterolemia), as an addition to diet and other treatments (e.g. LDL apheresis), or when these treatments are unsuitable;
• to reduce the risk of coronary heart disease in patients with atherosclerosis or diabetes, even if cholesterol levels are normal, in combination with diet and other treatments.

2. Important information before using Apo-Simva

When not to use Apo-Simva

• if the patient is allergic to simvastatin or any of the other ingredients of this medicine (listed in section 6)

• if there are currently liver function abnormalities

• if the patient is pregnant or breastfeeding

• if the patient is taking:

• itraconazole, ketoconazole, posaconazole or voriconazole (medicines used for fungal infections)

• erythromycin, clarithromycin or telithromycin (antibiotics used for bacterial infections)

• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (HIV protease inhibitors are used in the treatment of HIV infection)

• boceprevir or telaprevir (used in the treatment of hepatitis C virus infection)

• nefazodone (an antidepressant)

• cobicistat

• gemfibrozil (used to reduce cholesterol levels)

• cyclosporine (used in organ transplant patients)

• danazol (a synthetic hormone used in the treatment of endometriosis, a condition in which the tissue lining the uterus grows outside the uterus)

• if the patient is currently taking or has taken within the last 7 days the medicine fusidic acid (a medicine used to treat bacterial infections) orally or by injection. Taking fusidic acid together with Apo-Simva may lead to serious muscle problems (rhabdomyolysis).

Do not use Apo-Simva at doses higher than 40 mg if the patient is taking lomitapide
(used in the treatment of a severe and rare genetic disorder affecting cholesterol levels).
If in doubt whether any of the medicines listed above are being used, consult a
doctor.
Warnings and precautions
Before starting Apo-Simva, discuss with your doctor or pharmacist:

• any medical conditions the patient has had, including allergies
• if the patient drinks large amounts of alcohol
• if the patient has ever had liver disease. Apo-Simva may not be the right medicine for the patient
• if the patient is scheduled for surgery. Temporary discontinuation of simvastatin may be necessary
• if the patient is of Asian descent, as a different dose may be appropriate for this patient.

Your doctor should order a blood test before starting treatment with Apo-Simva and
during treatment if the patient has any liver abnormalities. The purpose of the test is
to assess liver function.
Your doctor may also order blood tests to check whether the patient's liver is functioning properly after starting Apo-Simva.
If the patient has diabetes or is at risk of developing diabetes, the doctor will closely monitor the patient during treatment with this medicine.
The patient may be at increased risk of developing diabetes if they have high blood sugar and lipid levels, overweight and high blood pressure.
Inform the doctor about serious lung diseases.
Contact the doctor immediately if the patient experiences unexplained muscle pain,
tenderness to touch or muscle weakness. This is because serious muscle disorders, including muscle breakdown leading to kidney failure, may rarely occur; very
rare cases of patient death have been reported.
Inform the doctor or pharmacist also if muscle weakness persists. Additional tests and
possibly additional medications may be necessary to diagnose and treat this condition.
Inform the doctor if the patient has or has had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen symptoms or lead to the development of myasthenia (see section 4).
The risk of muscle breakdown increases with higher doses of simvastatin and is greater in certain patients.
Consult your doctor if any of the following situations apply to the patient:

• the patient drinks large amounts of alcohol
• kidney diseases are present
• thyroid diseases are present
• the patient is 65 years of age or older
• the patient is female
• in the past, when taking cholesterol-lowering medicines called "statins" or "fibrates", harmful effects on the muscular system occurred
• the patient or their immediate family has a history of inherited muscle disorders.

Children and adolescents
The safety and efficacy of simvastatin have been studied in boys aged 10–17 years and in girls who started menstruation (periods) at least one year earlier (see section "How to use Apo-Simva"). Studies on the use of simvastatin in children under 10 years of age have not been conducted. For additional information, consult a doctor.
Apo-Simva and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
The medicines listed below may be known to the patient under another name, usually a brand name. This section does not list brand names but rather the active substance names or groups of active substances to which they belong. Therefore, carefully check the packaging or the patient leaflet included with the medicine to identify the active substance of the medicine being used.
It is especially important to inform the doctor if the patient is taking any of the following medicines. Taking simvastatin together with any of these medicines may increase the risk of muscle disorders (some of which are listed above in section "When not to use Apo-Simva"):

• If oral fusidic acid is required for the treatment of a bacterial infection, temporary discontinuation of this medicine will be necessary. The doctor will inform when it is safe to restart Apo-Simva. Concomitant use of Apo-Simva with fusidic acid may rarely lead to muscle weakness, tenderness or pain (rhabdomyolysis). Additional information on rhabdomyolysis is provided in section 4.
• Cyclosporine (a medicine commonly used in organ transplant patients)
• Danazol (a synthetic hormone used in the treatment of endometriosis, a condition in which the tissue lining the uterus grows outside the uterus)
• Medicines such as itraconazole or ketoconazole, fluconazole or posaconazole (used to treat fungal infections)
• Fibrates such as gemfibrozil and bezafibrate (medicines that reduce blood cholesterol levels)
• Erythromycin, clarithromycin, telithromycin or fusidic acid (used to treat bacterial infections). Do not use fusidic acid during treatment with simvastatin. See section 4.
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (medicines used in the treatment of AIDS)
• Antiviral medicines used in the treatment of hepatitis C virus infection, such as boceprevir, telaprevir, elbasvir or grazoprevir (used in the treatment of hepatitis C)
• Nefazodone (an antidepressant)
• Medicines containing the active substance cobicistat
• Amiodarone (a medicine used for heart rhythm disorders)
• Verapamil or diltiazem or amlodipine (medicines used for high blood pressure, angina with chest pain or other heart conditions)
• Lomitapide (used in the treatment of a severe and rare genetic disorder affecting cholesterol levels)
• Daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). The risk of muscle-related adverse effects may be greater when this medicine is taken during treatment with a statin (e.g. Apo-Simva). The doctor may decide to temporarily discontinue Apo-Simva.
• Colchicine (a medicine used in the treatment of gout)
• Ticagrelor (a medicine that reduces platelet aggregation).

In addition to the medicines listed above, inform your doctor or pharmacist about all medicines currently or recently taken, including those available without a prescription. In particular, mention the use of the following medicines:

• Medicines preventing blood clotting, such as warfarin, phenprocoumon, acenocoumarol (anticoagulants)
• Fenofibrate (another medicine reducing cholesterol levels)
• Niacin (another medicine reducing cholesterol levels)
• Rifampicin (a medicine used in the treatment of tuberculosis)

Inform your doctor if you are taking niacin (nicotinic acid) or any product containing niacin, and if you are of Asian descent.
If your doctor prescribes a new medicine, inform them that you are taking simvastatin.
Apo-Simva with food, drink and alcohol
Grapefruit juice contains one or more components that affect how certain medicines, including statins, are used by the body. Do not drink grapefruit juice.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant or plans to have a child, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
Do not use Apo-Simva if the patient is pregnant, suspects she may be pregnant or is planning to become pregnant. If the patient becomes pregnant while taking Apo-Simva, she should stop taking the medicine and contact her doctor immediately.
Breastfeeding
Do not use Apo-Simva if the patient is breastfeeding, as there is no information on whether simvastatin passes into breast milk.
Driving and using machines
Apo-Simva does not appear to affect the ability to drive or operate machinery. However, it should be noted that dizziness may occur in some patients after taking simvastatin.
Apo-Simva contains lactose
In addition to other ingredients, Apo-Simva contains a sugar called lactose. If the patient has previously been diagnosed with intolerance to certain sugars, they should consult a doctor before taking this medicine.

3. How to take Apo-Simva

This medicine should always be taken as directed by a physician or pharmacist. In case of doubt,
consult your physician or pharmacist.
While being treated with simvastatin, the patient should follow a cholesterol-lowering diet.
The recommended dose is 1 tablet or a dose of 5 mg, 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin
taken orally once daily.
The 80 mg dose is recommended only for adult patients with very high blood cholesterol levels and a high risk of cardiac complications, in whom treatment goals have not been achieved with lower doses.
The physician will determine the most appropriate dose for the patient depending on the patient's health status, concomitantly administered medications, and existing risk factors.
Use in children and adolescents
In children (aged 10 to 17 years), the recommended initial dose is 10 mg once daily in the evening.
The recommended maximum dose is 40 mg once daily.
Apo-Simva should be taken in the evening. The medicine may be taken with meals or independently of meals.
The usual starting dose is 10 mg, 20 mg, or in some cases 40 mg once daily.
If necessary, the physician may adjust the dose at intervals of at least four weeks up to a maximum dose of 80 mg once daily. Do not take more than 80 mg of simvastatin once daily.
The physician may prescribe lower doses, especially if the patient is taking other medicines listed above or if the patient has kidney disease. Apo-Simva should be taken until the physician decides to discontinue treatment.
If the physician has prescribed simvastatin together with any bile acid sequestrant (another cholesterol-lowering medicine), Apo-Simva should be taken at least two hours before or four hours after taking the bile acid-binding medicine.
Taking more Apo-Simva than recommended
If the patient has accidentally taken too many tablets, contact a physician or pharmacist immediately.
Missing a dose of Apo-Simva
If the patient realizes shortly after the scheduled time that a dose has been missed, the dose should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the next dose taken at the usual time. In case of doubt, consult your physician or pharmacist.
Do not take a double dose to make up for a missed dose.
Stopping Apo-Simva treatment
If the patient suddenly stops taking the medicine, blood cholesterol levels may rise again. Therefore, it is important to consult the physician before stopping treatment, even if the patient experiences physical discomfort. The physician will inform the patient whether stopping the medicine is possible and, if so, will advise on the best way to discontinue the medicine.
If you have any further questions about the use of this medicine, consult your physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following terms have been used to describe how frequently adverse reactions occur:
Common: affects less than 1 in 10 people
Uncommon: affects less than 1 in 100 people
Rare: affects less than 1 in 1,000 people
Very rare: affects less than 1 in 10,000 people
Not known: frequency cannot be estimated from the available data.
Rare: less than 1 in 1,000 people
If any of the following serious adverse reactions occur, stop taking the medicine immediately and contact your doctor or go to the emergency department of your nearest hospital.

• Muscle pain, tenderness, weakness or cramps. Rarely, muscle problems may be serious, including rhabdomyolysis (muscle breakdown) leading to kidney failure; very rarely, patient deaths have been reported.
• Hypersensitivity (allergic) reactions including:
• swelling of the face, tongue or throat, which may cause difficulty in breathing (angioedema), breathing difficulties
• severe muscle pain, especially in the arms and hips
• rash with muscle weakness in the limbs and neck
• joint pain or inflammation (rheumatoid arthritis)
• inflammation of blood vessels (vasculitis)
• unusual bruising, skin lesions and swelling, urticaria, photosensitivity, fever, sudden flushing
• difficulty breathing or fatigue
• symptoms of lupus-like syndrome (with rash, joint pain and effects on blood cells).
• Hepatitis with symptoms of yellowing of the skin and whites of the eyes (jaundice), itching, dark urine or pale stools, fatigue or weakness, loss of appetite, liver failure (very rare).
• Pancreatitis, often with severe abdominal pain.

The following adverse reactions have been reported rarely:

• low number of red blood cells (anaemia)
• numbness or weakness in arms or legs
• headache, tingling sensation, dizziness
• blurred vision; visual disturbances
• gastrointestinal disturbances (abdominal pain, constipation, flatulence, indigestion, diarrhoea, nausea, vomiting)
• rash, itching, hair loss
• weakness
• sleep disorders (very rare)
• poor memory (very rare), memory loss, confusion.

Very rare: affects less than 1 in 10,000 people
The following very rare serious adverse reactions have been reported:

• severe allergic reaction causing difficulty in breathing or dizziness (anaphylaxis)
• rash which may appear on the skin or cause ulceration of the mucous membranes in the mouth (lichenoid mucosal lesions)
• muscle damage
• gynaecomastia (enlargement of the breasts in males).

Not known: frequency cannot be estimated from the available data

• erectile dysfunction
• depression
• lung inflammation causing breathing problems, including persistent cough and/or shortness of breath or fever
• tendon damage, sometimes complicated by tendon rupture
• persistent muscle weakness
• myasthenia (a disease causing generalised muscle weakness, including in some cases muscles involved in breathing), ocular myasthenia (a disease causing weakness of the eye muscles). You should speak to your doctor if you experience weakness in the arms or legs that worsens with activity, double vision or drooping eyelids, difficulty swallowing or breathlessness.

As with other statins, the following adverse reactions have also been reported:

• sleep disturbances, including nightmares
• memory loss
• sexual dysfunction
• diabetes. The risk of developing diabetes is higher in patients with high blood glucose and lipid levels, overweight and high blood pressure. Your doctor will monitor your condition during treatment with this medicine.
• muscle pain, tenderness or weakness that is persistent; very rarely, these symptoms may not resolve after stopping treatment with simvastatin.

Laboratory test results
Increases in blood laboratory test values related to liver function and muscle enzymes (creatine kinase) have been observed.

Reporting of adverse reactions
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder in Poland. Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Apo-Simva

Keep this medicine out of sight and reach of children.
Keep this medicine in its original cardboard packaging. Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton or blister pack following the term "Expiry date:" (EXP:). The first two digits indicate the month, and the next four digits indicate the year.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via household waste or sewage. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Apo-Simva contains

• The active substance is simvastatin. Each coated tablet of Apo-Simva 10, Apo-Simva 20, or Apo-Simva 40 contains 10 mg, 20 mg, or 40 mg of simvastatin, respectively.
• Other ingredients are: Tablet core: monohydrate lactose, microcrystalline cellulose (E460), pregelatinized starch, butylated hydroxyanisole (E320), ascorbic acid (E300), citric acid (E330), colloidal anhydrous silica (E551), talc (E553b), magnesium stearate (E470b). Coating: hypromellose (E464), iron oxide red (E172), iron oxide yellow (E172), triethyl citrate (E1505), titanium dioxide (E171), talc (E553b), povidone (E1201).

What Apo-Simva looks like and contents of the pack
Apo-Simva 10: peach-colored, oval, biconvex coated tablet with a score line on one side. The Apo-Simva 10 tablet can be divided into two equal halves.
Apo-Simva 20: beige, oval, biconvex coated tablet.
Apo-Simva 40: brick-red, oval, biconvex coated tablet.
The carton pack contains 30 coated tablets (3 blisters of 10 tablets each).
Marketing Authorisation Holder:
Aurovitas Pharma Polska Sp. z o.o.
Sokratesa 13D lok.27
01-909 Warsaw
Poland
Manufacturer / Importer:
Zakłady Farmaceutyczne Polpharma S.A.
Pelplińska 19
83-200 Starogard Gdański
Poland