APO-SIMVA 20 mg Tablets

Contents of the leaflet

1. What is Apo-Simva and what is it used for
2. Important information before using Apo-Simva
   1. When not to use Apo-Simva
   2. Warnings and precautions
   3. Children and adolescents
   4. Apo-Simva and other medicines
   5. Apo-Simva with food, drink, and alcohol
   6. Pregnancy, breastfeeding, and fertility
   7. Driving and using machines
   8. Apo-Simva contains lactose
3. How to use Apo-Simva
   1. Use in children and adolescents
   2. Taking a higher dose of Apo-Simva than recommended
   3. Forgetting to take Apo-Simva
   4. Stopping Apo-Simva
4. Possible side effects
   1. If the patient experiences any of the following serious side effects, they should stop taking the medicine and contact their doctor immediately or go to the emergency department of their nearest hospital.
   2. Reporting side effects
5. How to store Apo-Simva
6. Contents of the pack and other information
   1. What Apo-Simva contains
   2. What Apo-Simva looks like and contents of the pack
   3. Marketing authorization holder:
   4. Aurovitas Pharma Polska Sp. z o.o.
   5. Manufacturer/importer:
   6. Zakłady Farmaceutyczne Polpharma S.A.
   7. Date of last revision of the leaflet: 09.2024

1. What is Apo-Simva and what is it 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 the level of cholesterol and triglycerides in the blood, and to increase the level of "good" cholesterol (HDL cholesterol). Cholesterol is one of several fatty substances found in the blood. Total cholesterol is mainly made up of LDL cholesterol and HDL cholesterol. LDL cholesterol is often called "bad" cholesterol because it can build up on the walls of arteries, forming plaques. Eventually, these plaques can cause the arteries to narrow, restricting blood flow to vital organs such as the heart and brain. Reduced blood flow can lead to heart attacks or strokes. 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 found in the blood that can increase the risk of heart disease. While taking this medicine, you should follow a cholesterol-lowering diet.

• to reduce the level of cholesterol and triglycerides in the blood when the response to diet and other treatments (such as exercise, weight loss) is not sufficient,
• to reduce the level of inherited high cholesterol in the blood (homozygous familial hypercholesterolemia) as an adjunct to diet and other treatments (such as LDL apheresis) or when these treatments are not appropriate,
• to reduce the risk of coronary artery disease if the patient has atherosclerosis (hardening of the arteries) or diabetes, even if the cholesterol level is 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 the medicine (listed in section 6)
• if the patient currently has liver problems
• if the patient is pregnant or breastfeeding
• if the patient is taking:
• itraconazole, ketoconazole, posaconazole, or voriconazole (medicines used to treat fungal infections)
• erythromycin, clarithromycin, or telithromycin (antibiotics used to treat bacterial infections)
• HIV protease inhibitors, such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors are used to treat HIV infections)
• boceprevir or telaprevir (used to treat hepatitis C virus infection)
• nefazodone (an antidepressant)
• cobicistat
• gemfibrozil (used to lower cholesterol levels)
• cyclosporine (used in patients who have had organ transplants)
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)
• if the patient is currently taking or has taken within the last 7 days a medicine called fusidic acid (an antibiotic used to treat bacterial infections) orally or by injection. Taking fusidic acid with Apo-Simva can lead to serious muscle problems (rhabdomyolysis).

Apo-Simva should not be used in doses greater than 40 mg if the patient is taking lomitapide (used to treat a rare genetic disorder of high cholesterol levels). If in doubt about the use of any of the above medicines, the patient should consult their doctor.

Warnings and precautions

Before starting to take Apo-Simva, the patient should discuss the following with their doctor or pharmacist:

• any diseases the patient has had, including allergies
• if the patient consumes large amounts of alcohol
• if the patient has ever had liver disease. Apo-Simva may not be suitable for the patient
• if the patient is scheduled for surgery. It may be necessary to temporarily stop taking simvastatin
• if the patient is of Asian origin, as a different dose may be suitable for the patient.

The doctor should order a blood test before starting Apo-Simva and during treatment if the patient has any liver problems. The test will assess liver function. The doctor may also order a blood test to check if the patient's liver is working properly after taking Apo-Simva. If the patient has diabetes or is at risk of developing diabetes, the doctor will closely monitor the patient's condition while taking this medicine. The patient may be at risk of developing diabetes if they have high blood sugar and lipid levels, are overweight, and have high blood pressure.

Children and adolescents

The safety and efficacy of simvastatin have been studied in boys aged 10-17 years and girls who have started menstruation (at least one year before). No studies have been conducted in children under the age of 10. For more information, the patient should consult their doctor.

Apo-Simva and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. The following medicines may be known to the patient by a different name, usually a trade name. This section does not list trade names of medicines, but the name of the active substance or group of active substances. Therefore, the patient should carefully check the packaging or the patient information leaflet to see what the active substance of the medicine is. It is especially important to tell the doctor if the patient is taking any of the following medicines, as taking simvastatin with any of these medicines can increase the risk of muscle problems (some of which are listed above in the "When not to use Apo-Simva" section):

• cyclosporine (a medicine often used in patients who have had organ transplants)
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of 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 used to lower cholesterol levels in the blood)
• erythromycin, clarithromycin, telithromycin, or fusidic acid (used to treat bacterial infections). Do not take fusidic acid while taking Apo-Simva. See section 4.
• HIV protease inhibitors, such as indinavir, nelfinavir, ritonavir, and saquinavir (medicines used to treat AIDS)
• antiviral medicines used to treat hepatitis C virus infection, such as boceprevir, telaprevir, elbasvir, or grazoprevir
• nefazodone (an antidepressant)
• medicines containing the active substance cobicistat
• amiodarone (a medicine used to treat irregular heartbeats)
• verapamil or diltiazem or amlodipine (medicines used to treat high blood pressure, angina, or other heart conditions)
• lomitapide (used to treat a rare genetic disorder of high cholesterol levels)
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). It is possible that the risk of muscle problems may be higher when this medicine is taken with simvastatin (e.g., Apo-Simva). The doctor may decide to stop Apo-Simva for a while.
• colchicine (a medicine used to treat gout)
• tikagrelor (a medicine that reduces platelet aggregation).

In addition to the medicines listed above, the patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, including those that are available without a prescription. In particular, the patient should mention the use of the following medicines:

• medicines that prevent blood clots, such as warfarin, phenprocoumon, acenocoumarol (anticoagulants)
• fenofibrate (another medicine used to lower cholesterol levels)
• niacin (another medicine used to lower cholesterol levels)
• rifampicin (a medicine used to treat tuberculosis)

The patient should tell their doctor about taking niacin (nicotinic acid) or any product containing niacin, and if they are of Asian origin. If the doctor prescribes a new medicine, the patient should tell them about taking simvastatin.

Apo-Simva with food, drink, and alcohol

Grapefruit juice contains one or more ingredients that affect the way the body uses some medicines, including simvastatin. The patient should not drink grapefruit juice.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine. Pregnancy The patient should not use Apo-Simva if they are pregnant, think they may be pregnant, or plan to have a child. If the patient becomes pregnant while taking Apo-Simva, they should stop taking the medicine and contact their doctor immediately. Breastfeeding The patient should not use Apo-Simva if they are breastfeeding, as there is no information on the passage of simvastatin into breast milk.

Driving and using machines

Apo-Simva is unlikely to affect the patient's ability to drive or use machines. However, the patient should take into account that some patients may experience dizziness after taking simvastatin.

Apo-Simva contains lactose

In addition to other ingredients, Apo-Simva contains a sugar called lactose. If the patient has been diagnosed with intolerance to some sugars, they should contact their doctor before taking the medicine.

3. How to use Apo-Simva

The patient should always use this medicine exactly as their doctor or pharmacist has told them. If they are unsure, they should ask their doctor or pharmacist. While taking simvastatin, the patient should be on 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 a day. A dose of 80 mg is recommended only for adult patients with very high cholesterol levels in the blood and a high risk of heart complications, who have not achieved their treatment goals with lower doses. The doctor will determine the most suitable dose of the medicine for the patient, depending on their health, the medicines they are taking, and the risk factors they have.

Use in children and adolescents

In children (aged 10-17 years), the recommended starting dose is 10 mg per day in the evening. The recommended maximum dose is 40 mg per day. Apo-Simva should be taken in the evening. The medicine can be taken with or without food. The usual starting dose is 10 mg, 20 mg, or in some cases 40 mg per day. If necessary, the doctor may adjust the dose at intervals of at least 4 weeks up to a maximum dose of 80 mg once a day. The patient should not take more than 80 mg of simvastatin once a day. The doctor may prescribe lower doses, especially if the patient is taking other medicines listed above or has kidney disease. Apo-Simva should be taken until the doctor decides to stop the treatment. If the doctor has prescribed simvastatin with a bile acid sequestrant (another medicine used to lower cholesterol levels), Apo-Simva should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking a higher dose of Apo-Simva than recommended

If the patient has taken too many tablets by mistake, they should contact their doctor or pharmacist immediately.

Forgetting to take Apo-Simva

If the patient realizes they have forgotten to take the prescribed dose soon after the time they should have taken it, they should take it as soon as possible. However, if it is almost time for the next dose, they should skip the missed dose and take the next dose at the usual time. In case of doubt, the patient should ask their doctor or pharmacist. The patient should not take a double dose to make up for a forgotten dose.

Stopping Apo-Simva

If the patient suddenly stops taking the medicine, their cholesterol level may rise again. Therefore, it is important to consult the doctor before stopping the medicine, even if the patient feels unwell. The doctor will tell the patient whether it is possible to stop the medicine and will recommend the best way to stop taking it. If the patient has any further doubts about taking the medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Apo-Simva can cause side effects, although not everybody gets them. The following terms have been used to describe how often side effects occur:

• Common: less than 1 in 10 people
• Uncommon: less than 1 in 100 people
• Rare: less than 1 in 1000 people
• Very rare: less than 1 in 10,000 people
• Not known: frequency cannot be estimated from the available data

If the patient experiences any of the following serious side effects, they should stop taking the medicine and contact their doctor immediately or go to the emergency department of their nearest hospital.

• Muscle pain, tenderness, or weakness, or muscle cramps. Rarely, muscle problems can be serious, including muscle breakdown, which can lead to kidney failure; very rarely, this can be life-threatening.
• Allergic reactions, including:
• swelling of the face, tongue, or throat, which can cause difficulty breathing (angioedema), difficulty breathing
• severe muscle pain, especially in the arms and legs
• rash with muscle weakness and neck and shoulder stiffness
• joint pain or inflammation, or muscle pain
• inflammation of blood vessels (vasculitis),
• unusual bruising, skin rash, and swelling, hives, sensitivity to sunlight, fever, flushing
• difficulty breathing or feeling tired
• symptoms of lupus-like syndrome (with rash, joint pain, and effects on blood cells).
• Liver inflammation with symptoms of yellowing of the skin and whites of the eyes, itching, dark urine, or pale stools, fatigue, or weakness, loss of appetite, liver failure (very rare).
• Pancreatitis, often with severe abdominal pain.

The following side effects have been reported rarely:

• low red blood cell count (anemia)
• numbness or weakness in the arms or legs
• headache, feeling of tingling, dizziness
• blurred vision; vision problems
• digestive problems (abdominal pain, constipation, bloating with gas, indigestion, diarrhea, nausea, vomiting)
• rash, itching, hair loss
• weakness
• sleep disturbances (very rare)
• poor memory (very rare), memory loss, confusion.

Very rare: less than 1 in 10,000 people

• a severe allergic reaction that can cause difficulty breathing or dizziness (anaphylaxis)
• a rash that can occur on the skin or mouth ulcers (drug-induced lupus-like syndrome)
• muscle damage
• breast enlargement in men (gynecomastia).

Not known: frequency cannot be estimated from the available data

• erectile dysfunction
• depression
• inflammation of the lungs that can cause breathing problems, including persistent cough and/or shortness of breath or fever
• tendon damage, sometimes complicated by tendon rupture
• prolonged muscle weakness
• myasthenia (a disease that causes general muscle weakness, including in some cases muscles involved in breathing), ocular myasthenia (a disease that causes muscle weakness in the eyes). The patient should talk to their doctor if they experience weakness in their arms or legs, worsening after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or shortness of breath.

Similar to other statins, the following side effects have also been reported:

• sleep disturbances, including nightmares
• memory loss
• sexual problems
• diabetes. The risk of developing diabetes is higher in patients with high blood sugar and lipid levels, who are overweight, and have high blood pressure. The doctor will monitor the patient's condition while taking this medicine
• muscle pain, tenderness, or weakness that can be persistent; very rarely, these symptoms may not resolve after stopping simvastatin treatment.

Laboratory test results have shown increased values for some blood tests that measure liver function and muscle enzymes (creatine kinase).

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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. Side effects can also be reported to the marketing authorization holder in Poland. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Apo-Simva

The medicine should be stored out of the sight and reach of children. The medicine should be stored in its original carton. Do not store above 25°C. Do not use this medicine after the expiry date stated on the carton or blister after "EXP:". The first two digits indicate the month, the next four digits indicate the year. The expiry date refers to the last day of the month stated. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Apo-Simva contains

• The active substance of the medicine is simvastatin. Each film-coated tablet of Apo-Simva 10, Apo-Simva 20, or Apo-Simva 40 contains 10 mg, 20 mg, or 40 mg of simvastatin, respectively.
• The other ingredients are: Tablet core:lactose monohydrate, microcrystalline cellulose (E460), pregelatinized starch, butylhydroxyanisole (E320), ascorbic acid (E300), citric acid (E330), colloidal anhydrous silica (E551), talc (E553b), magnesium stearate (E470b). Coating:hypromellose (E464), red iron oxide (E172), yellow iron oxide (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 film-coated tablet with a notch on one side. The Apo-Simva 10 tablet can be divided into two halves. Apo-Simva 20: beige, oval, biconvex film-coated tablet. Apo-Simva 40: brick-red, oval, biconvex film-coated tablet. The carton contains 30 film-coated tablets (3 blisters of 10 tablets each).

Marketing authorization holder:

Aurovitas Pharma Polska Sp. z o.o.

ul. Sokratesa 13D lok.27
01-909 Warsaw
Poland

Manufacturer/importer:

Zakłady Farmaceutyczne Polpharma S.A.

Pelplińska 19
83-200 Starogard Gdański
Poland

Date of last revision of the leaflet: 09.2024