Krustat

Patient Information Leaflet

KRUSTAT 20 mg film-coated tablets, 40 mg film-coated tablets

simvastatin
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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What KRUSTAT is and what it is used for

KRUSTAT contains the active substance simvastatin. KRUSTAT is a medicine used to lower
levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fats known as triglycerides
in the blood. In addition, KRUSTAT increases levels of "good" cholesterol (HDL cholesterol).
KRUSTAT belongs to a group of medicines called statins.
Cholesterol is one of several types of fat present in the bloodstream. Total cholesterol is made
up mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can build up in the walls of arteries,
forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing
can slow down or block blood flow to vital organs such as the heart and brain. This blockage of
blood flow can cause a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent "bad" cholesterol
from building up in the arteries and protects against heart disease.
Triglycerides are another type of fat in the blood that may increase the risk of heart disease.
You must follow a cholesterol-lowering diet while taking this medicine.
KRUSTAT is used in addition to diet to lower cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia) or elevated levels of fats in the blood (mixed hyperlipidemia)
• an inherited condition (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments
• coronary heart disease (CHD) or are at high risk of CHD (because you have diabetes, have had a stroke, or have another blood vessel disease). KRUSTAT can prolong survival by reducing the risk of heart-related problems, regardless of blood cholesterol levels. In most people, high cholesterol does not cause immediate symptoms. Your doctor can check your cholesterol levels with a simple blood test. Visit your doctor regularly, keep track of your cholesterol values, and discuss cholesterol targets with your doctor.

2. What you need to know before taking KRUSTAT

Do not take KRUSTAT:

• if you are allergic (hypersensitive) to simvastatin or to any of the other ingredients of this medicine (listed in section 6: Contents of the pack and other information)
• if you currently have liver problems
• if you are pregnant or breastfeeding
• if you are taking a medicine(s) containing any of the following active substances:
  o itraconazole, ketoconazole, posaconazole, or voriconazole (used to treat fungal infections)
  o erythromycin, clarithromycin, or telithromycin (used to treat infections)
  o HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors are used for HIV infections)
  o boceprevir or telaprevir (used to treat hepatitis C virus infection)
  o nefazodone (used to treat depression)
  o cobicistat or gemfibrozil (used to lower cholesterol)
  o ciclosporin (used in organ transplant patients)
  o danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).
  • If you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine used to treat bacterial infection). The combination of fusidic acid and KRUSTAT may cause serious muscle problems (rhabdomyolysis).

Do not take more than 40 mg of KRUSTAT if you are taking lomitapide (used to treat a rare, genetic, severe cholesterol condition).
Ask your doctor for advice if you are unsure whether the medicine you are taking is among those listed above.

Warnings and precautions
Tell your doctor:
o about all your medical conditions, including allergies
o if you consume large amounts of alcohol
o if you have ever had liver disease. In this case, KRUSTAT may not be suitable for you
o if you are due to undergo surgery. You may need to stop taking KRUSTAT temporarily
o if you are of Asian origin, as you may require a different dose
o 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 cause its onset (see section 4).

Your doctor will perform a blood test before starting KRUSTAT and if you develop symptoms of liver problems while taking KRUSTAT. This test checks whether your liver is functioning properly.
Your doctor may also prescribe periodic blood tests to monitor liver function after starting treatment with KRUSTAT.

While taking this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. Risk factors for developing diabetes include high levels of sugar and fats in the blood, being overweight, and having high blood pressure.
Inform your doctor if you have a serious lung disease.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. This is because, rarely, muscle problems can be serious and may include muscle tissue damage leading to kidney damage; very rarely, cases of death have occurred.

The risk of muscle injury is higher at higher doses of KRUSTAT, particularly with the 80 mg dose. The risk of muscle injury is also increased in certain patients. Talk to your doctor if any of the following conditions apply to you:

• you consume large amounts of alcohol
• you have kidney problems
• you have thyroid problems
• you are 65 years of age or older
• you are female
• you have previously experienced muscle problems while taking cholesterol-lowering medicines known as “statins” or fibrates
• you or a close family member has a hereditary muscle disease.

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.

Children and adolescents
The safety and efficacy of simvastatin have been studied in adolescents aged 10 to 17 years and in girls who have had menstrual periods (menstruation) for at least one year (see section 3: How to take KRUSTAT). Simvastatin has not been studied in children under 10 years of age. For further information, consult your doctor.

Other medicines and KRUSTAT
Inform your doctor if you are currently taking, have recently taken, or might take any other medicine containing any of the following active substances. Taking KRUSTAT with any of the following medicines may increase the risk of muscle problems (some of these have already been listed in the section “Do not take KRUSTAT”):

• If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart KRUSTAT treatment. Taking KRUSTAT with fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). See more information on rhabdomyolysis in section 4.

• ciclosporin (often used in organ transplant patients)

• danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)

• medicines containing active substances such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections)

• fibrates with active substances such as gemfibrozil and bezafibrate (used to reduce cholesterol)

• erythromycin, clarithromycin, or telithromycin (used to treat bacterial infections)

• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS)

• antiviral agents for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C virus infection)

• nefazodone (used to treat depression)

• medicines containing the active substance cobicistat

• amiodarone (used to treat irregular heartbeat)

• verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart conditions)

• lomitapide (used to treat a rare, genetic, severe cholesterol condition)

• colchicine (used to treat gout)

As with the medicines listed above, inform your doctor or pharmacist if you are taking or have recently taken any other medicine, including those not requiring a prescription. In particular, inform your doctor if you are taking a medicine(s) containing any of the following active substances:

• medicines with an active substance to prevent blood clots, such as warfarin, phenprocoumon, or acenocoumarol (anticoagulants)
• fenofibrate (also used to lower cholesterol)
• niacin (also used to lower cholesterol)
• rifampicin (used to treat tuberculosis).

You should also inform any doctor prescribing a new medicine that you are taking KRUSTAT.

KRUSTAT with food and drink
Grapefruit juice contains one or more substances that alter how the body processes certain medicines, including KRUSTAT. Consumption of grapefruit juice should be avoided.

Pregnancy and breastfeeding
Do not use KRUSTAT if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking KRUSTAT, stop treatment immediately and contact your doctor.
Do not use KRUSTAT while breastfeeding, as it is not known whether the medicine passes into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
KRUSTAT is not expected to affect your ability to drive or operate machinery. However, you should be aware that dizziness has been reported after taking KRUSTAT.

KRUSTAT contains lactose
KRUSTAT tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.

3. HOW TO TAKE KRUSTAT

Your doctor will determine the appropriate tablet dosage for you based on your condition, your current treatment, and your risk profile.
Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
During treatment with KRUSTAT, you must follow a diet aimed at reducing cholesterol levels.

Dosage:
The usual dose of KRUSTAT is 20 mg or 40 mg taken orally once daily.

Adults:
The usual starting dose is generally 20 mg, or in some cases, 40 mg per day. Your doctor may adjust the dose after at least 4 weeks, up to a maximum of 80 mg per day. Do not take more than 80 mg per day.
Your doctor may prescribe lower doses of simvastatin, especially if you are taking any of the medicines listed above or have certain kidney problems.
The 80 mg dose is recommended only for adult patients with very high cholesterol levels and a high risk of heart disease who have not reached their target cholesterol levels with lower doses.

Use in children and adolescents:
For children (aged 10–17 years), the usual recommended starting dose of simvastatin is 10 mg daily, taken in the evening. The maximum recommended dose is 40 mg per day.

Method of administration:
Take KRUSTAT in the evening. It can be taken regardless of meals. Continue taking KRUSTAT unless your doctor tells you to stop treatment.
If your doctor has prescribed KRUSTAT together with another cholesterol-lowering medicine containing a bile acid sequestrant, you must take KRUSTAT at least 2 hours before or 4 hours after taking the bile acid sequestrant medicine.

If you take more KRUSTAT than you should

• Contact your doctor or pharmacist.

If you forget to take KRUSTAT

• Do not take a double dose to make up for the missed tablet; take only the usual dose of KRUSTAT the next day at the usual time.

If you stop taking KRUSTAT

• Talk to your doctor or pharmacist, as your cholesterol levels may rise again.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, KRUSTAT can cause side effects, although not everyone experiences them.
The following terms are used to describe how frequently side effects occur:

• Rare (may affect up to 1 in 1,000 people).
• Very rare (may affect up to 1 in 10,000 people).
• Not known (frequency cannot be estimated from the available data).

The following serious side effects have been reported in rare cases.
If you experience any of the following serious side effects, you must stop treatment and contact your doctor immediately or go to the nearest hospital emergency department:

• muscle pain, tenderness, weakness, or cramps; muscle breakdown (rhabdomyolysis) (may affect up to 1 in 10,000 people). In rare cases, these muscle problems may be severe and may include muscle tissue injury leading to kidney damage; and very rarely, cases of death have been reported
• hypersensitivity reactions (allergies) including:
  • swelling of the face, tongue, and throat, which may cause difficulty breathing (angioedema)
  • severe muscle pain, usually in the shoulders or hips
  • skin rash with weakness in the legs and neck muscles
  • joint pain or inflammation (polymyalgia rheumatica)
  • inflammation of blood vessels (vasculitis)
  • unusual bruising, skin rash, and swelling (dermatomyositis), hives, skin sensitivity to sunlight, fever, hot flushes
  • shortness of breath (dyspnea) and feeling unwell
  • lupus-like symptoms (including skin rash, joint problems, and effects on blood cells)
• liver inflammation with the following symptoms: yellowing of the skin and eyes (jaundice), itching, dark urine or pale stools, feeling tired or weak, loss of appetite, liver failure (very rare)
• inflammation of the pancreas, often associated with severe abdominal pain.

The following very rare serious side effect has been reported:

• a severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis)

The following side effects have also been reported rarely:

• decrease in red blood cell count (anaemia)
• numbness or weakness in the arms and legs
• headache, tingling sensation, dizziness
• digestive disorders (abdominal pain, constipation, flatulence, indigestion, diarrhoea, nausea, vomiting)
• skin rash, itching, hair loss
• weakness
• difficulty sleeping (very rare)
• poor memory (very rare), memory loss, confusion.

Additionally, the following side effects have been reported in people taking medicines containing the active substance simvastatin:

• blurred vision and visual impairment (may affect up to 1 in 1,000 people)
• skin rash, which may also appear as mouth ulcers (drug-induced lichenoid eruption) (may affect up to 1 in 10,000 people)
• gynaecomastia (enlargement of breast tissue in men) (may affect up to 1 in 10,000 people)

The following side effects have also been reported with unknown frequency (frequency cannot be estimated from the available data):

• erectile dysfunction
• depression
• lung inflammation causing breathing problems, including persistent cough and/or shortness of breath and fever
• tendon problems, sometimes complicated by tendon rupture
• 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). Consult your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or laboured breathing.

Other possible side effects reported with some statins:

• sleep disorders, including nightmares
• sexual difficulties
• diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine
• muscle pain, tenderness, or weakness that is persistent and may not resolve after stopping simvastatin treatment (frequency not known).

Diagnostic tests
Increases in certain blood test values related to liver function and a muscle enzyme (creatine kinase) have been observed.

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 the following website: 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 KRUSTAT

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Store below 25°C.
Do not dispose of medicines 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 KRUSTAT contains
The active substance is simvastatin (20 mg, 40 mg).
KRUSTAT 20 mg film-coated tablets
Each tablet contains:
Active substance: simvastatin 20 mg
Excipients: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, yellow iron oxide.
KRUSTAT 40 mg film-coated tablets
Each tablet contains:
Active substance: simvastatin 40 mg
Excipients: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, red iron oxide.
Pharmaceutical form and contents
KRUSTAT 20 mg film-coated tablets (pack sizes: 10 and 28 tablets of 20 mg).
KRUSTAT 40 mg film-coated tablets (pack sizes: 10 and 28 tablets of 40 mg).
Marketing Authorization Holder
S.F. Group Srl – via Tiburtina, 1143 – 00156 Roma
Manufacturer
Special Product’s Line S.p.A. - Via Paduni, 240 – 03012 Anagni (Frosinone).