Apo-simva 40

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 reduce the level of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. Additionally, Apo-Simva increases the level of "good" cholesterol (HDL cholesterol). Cholesterol is one of several fatty substances present 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 or blocking the flow of blood to vital organs, such as the heart and brain. Blocking the flow of blood can lead to a 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 present in the blood, which can increase the risk of developing heart disease. While taking this medicine, you should follow a cholesterol-reducing diet. Apo-Simva is used as a supplement to a cholesterol-reducing 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 inherited high levels of cholesterol in the blood (familial homozygous hypercholesterolemia) as a supplement to diet and other treatments (such as LDL apheresis) or when these treatments are not suitable,
• 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 reduce cholesterol levels)
• cyclosporine (used in patients who have had organ transplants)
• danazol (a synthetic hormone used to treat endometriosis, a disease 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 may 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). In case of doubt, whether any of the above-mentioned medicines are being taken, the patient should consult a doctor.

Warnings and precautions

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

• all diseases that 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 this patient.

The doctor should order a blood test before starting Apo-Simva and during treatment if the patient has any liver problems. The purpose of the test is to assess liver function. The doctor may also recommend 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. The patient should inform their doctor about any serious lung diseases.

The patient should contact their doctor immediately if they experience unexplained muscle pain, tenderness, or weakness. This is because rare but serious muscle problems can occur, including muscle breakdown that can lead to kidney failure; very

rarely, death has been reported.

The doctor or pharmacist should also be informed if muscle weakness persists. To diagnose and treat this condition, additional tests and medications may be necessary.

If the patient has or has had myasthenia (a disease that causes general muscle weakness, including muscles involved in breathing) or myasthenic syndrome (a disease that causes muscle weakness, especially in the eyes), because statins can sometimes exacerbate symptoms of the disease or lead to the development of myasthenia (see section 4). The risk of muscle breakdown increases with the dose of simvastatin and is higher in some patients. The patient should consult their doctor if any of the following situations apply to them:

• the patient consumes large amounts of alcohol
• the patient has kidney disease
• the patient has thyroid disease
• the patient is 65 years of age or older
• the patient is female
• the patient has previously experienced muscle problems while taking cholesterol-lowering medicines called "statins" or "fibrates"
• the patient or their close relatives have had genetic muscle disorders.

Children and adolescents

The safety and efficacy of simvastatin have been studied in boys aged 10-17 years and girls who have started menstruating (menstruation) at least one year earlier (see "How to use Apo-Simva"). No studies have been conducted on the use of simvastatin 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 under a different name, usually a trade name. In this section, the trade names of medicines are not listed, but rather the names of the active substances or groups of active substances to which they belong. 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. Taking simvastatin with any of these medicines may increase the risk of muscle problems (some of which are listed above in the "When not to use Apo-Simva" section):

If it is necessary to take fusidic acid orally to treat a bacterial infection, it may be necessary to temporarily stop taking Apo-Simva. The doctor will inform the patient when it is safe to restart Apo-Simva.

Taking Apo-Simva with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). Additional information on rhabdomyolysis can be found in section 4.

• Cyclosporine (a medicine often used in patients who have had organ transplants)
• Danazol (a synthetic hormone used to treat endometriosis, a disease 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 (used to treat hepatitis C virus infection)
• Neefazodone (an antidepressant)
• Medicines containing the active substance cobicistat
• Amiodarone (a medicine used to treat heart rhythm disorders)
• Verapamil or diltiazem or amlodipine (medicines used to treat high blood pressure, angina pectoris with chest pain, or other heart diseases)
• 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 muscle-related side effects may be greater 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)
• Ticagrelor (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 inform them about taking simvastatin.

Apo-Simva with food, drink, and alcohol

Grapefruit juice contains one or more ingredients that affect the use of some medicines by the body, 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 data on the passage of simvastatin into breast milk.

Driving and using machines

Apo-Simva does not appear to affect the 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 consult their doctor before taking the medicine.

3. How to use Apo-Simva

This medicine should always be used as directed by the doctor or pharmacist. If the patient has any doubts, they should consult their doctor or pharmacist. While taking simvastatin, the patient should be on a cholesterol-reducing 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 treatment goals with lower doses. The doctor will determine the most suitable dose of the medicine for the patient based on their health, medications taken concurrently, and risk factors.

Use in children and adolescents

In children (aged 10-17 years), the recommended initial 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 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 cholesterol-lowering medicine), 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.

Missing a dose of Apo-Simva

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

Stopping Apo-Simva

If the patient suddenly stops taking the medicine, their cholesterol level may increase again. Therefore, it is essential to consult a doctor before stopping the medicine, even if the patient experiences physical discomfort. The doctor will inform the patient whether it is possible to stop the medicine and recommend the best way to stop 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 1,000 people Very rare: less than 1 in 10,000 people Unknown: 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 or go to the emergency room immediately.

• Muscle pain, tenderness, or weakness, or muscle cramps. Rarely, muscle problems can be serious, including muscle breakdown that can lead to kidney failure; very rarely, death has been reported.
• 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 hips
• rash with muscle weakness in the arms and neck
• joint pain or inflammation (polymyalgia rheumatica)
• inflammation of blood vessels (vasculitis),
• unusual bruising, skin rashes, and swelling, hives, sensitivity to sunlight, fever, flushing,
• difficulty breathing or fatigue
• 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, tingling, dizziness
• blurred vision; vision disturbances
• digestive disorders (abdominal pain, constipation, bloating with gas, indigestion, diarrhea, nausea, vomiting)
• rash, itching, hair loss
• weakness
• sleep disorders (very rare)
• poor memory (very rare), memory loss, confusion.

Very rare: less than 1 in 10,000 people
The following very rare but serious side effects have been reported:

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

Unknown: 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
• persistent muscle weakness
• myasthenia (a disease that causes general muscle weakness, including muscles involved in breathing), myasthenic syndrome (a disease that causes muscle weakness, especially in the eyes). The patient should talk to their doctor if they experience muscle weakness in the 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 disorders, including nightmares
• memory loss
• sexual disorders
• diabetes. The risk of developing diabetes is higher in patients with high blood sugar and lipid levels, overweight, and 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 Increased values of some laboratory blood tests for liver function and muscle enzymes (creatine kinase) have been observed.

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 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 "Expiry date:" (EXP:). The first two digits indicate the month, the next four digits indicate the year. The expiry date indicates the last day of the specified month. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. 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.
• Other ingredients are: 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), 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 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