Mizetam

Package leaflet: information for the patient

Mizetam, 10 mg + 10 mg, tablets
Mizetam, 10 mg + 20 mg, tablets
Mizetam, 10 mg + 40 mg, tablets
Mizetam, 10 mg + 80 mg, tablets
Ezetimibe + Atorvastatin
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Mizetam is and what it is used for

Mizetam is a medicine used to reduce high levels of cholesterol. Mizetam contains ezetimibe and atorvastatin.
Mizetam is used in adults to reduce total cholesterol levels, including "bad" cholesterol (LDL cholesterol), and fat substances called triglycerides in the blood. Additionally, Mizetam increases levels of "good" cholesterol (HDL cholesterol).
Mizetam works through two mechanisms to reduce cholesterol levels: it reduces cholesterol absorption in the gastrointestinal tract and inhibits cholesterol production in the body.
Cholesterol is one of several fatty substances present in the bloodstream. 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 may 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 "bad" cholesterol from depositing in the arteries and helps protect against heart disease.
Triglycerides are another type of fat in the blood that may contribute to an increased risk of heart disease.
Mizetam is used in patients in whom diet alone is not sufficient to control cholesterol levels. While taking this medicine, you should continue to follow a cholesterol-lowering diet.
If you have heart disease, Mizetam reduces the risk of heart attack, stroke, procedures to improve blood flow to the heart, or hospitalization due to chest pain.
Your doctor may prescribe Mizetam if you are already taking both atorvastatin and ezetimibe at the doses contained in this medicine.
Mizetam does not affect body weight reduction.

2. Important information before taking Mizetam

When not to take Mizetam:

• if the patient is allergic to atorvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6).
• if the patient currently has or has previously had liver disease.
• if the patient has unexplained abnormal results in blood tests for liver function.
• if the patient is of childbearing age and is not using an effective method of contraception.
• if the patient is pregnant, planning to become pregnant, or breastfeeding.
• if the patient is taking medicines containing glecaprevir and pibrentasvir for the treatment of hepatitis C virus infection.
• if oral fusidic acid must be taken to treat a bacterial infection, the use of this medicine should be stopped immediately. The doctor will inform the patient when it is safe to restart taking Mizetam. Taking Mizetam with fusidic acid may rarely lead to weakness, tenderness or pain in the muscles (rhabdomyolysis). For further information about rhabdomyolysis, see section 4.

Warnings and precautions
Before starting Mizetam, discuss with your doctor or pharmacist if:

• the patient currently has or has previously had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), because statins may sometimes worsen symptoms or lead to the development of myasthenia (see section 4).
• the patient has previously had a haemorrhagic stroke or has small fluid-filled sacs in the brain from previous strokes.
• the patient has kidney disease.
• the patient has hypothyroidism (underactive thyroid).
• the patient has recurrent or unexplained muscle pain, or has had muscle disease, or if muscle disease runs in the family.
• the patient previously experienced muscle-related symptoms during treatment with other lipid-lowering medicines (e.g. other "statins" or "fibrates").
• the patient is currently taking or has taken within the last 7 days an oral or injectable form of the medicine called fusidic acid (used to treat bacterial infections). The combination of fusidic acid and a medicine containing ezetimibe and atorvastatin may lead to serious consequences including muscle problems (rhabdomyolysis).
• the patient regularly consumes large amounts of alcohol.
• the patient has previously had liver disease.
• the patient is over 70 years of age.

Contact your doctor immediately if you experience unexplained
muscle pain, tenderness or weakness while taking Mizetam. In rare
cases, muscle-related symptoms may be serious and may include muscle breakdown leading to kidney damage.
Before taking Mizetam, consult your doctor or pharmacist:

• if the patient has severe respiratory insufficiency.

If any of the situations listed above apply to the patient (or if the patient is unsure), they should
consult their doctor or pharmacist before taking Mizetam, as the doctor may need to perform blood tests before starting treatment and periodically during therapy to assess the risk of muscle-related adverse effects. The risk of muscle-related adverse effects, such as rhabdomyolysis (breakdown of skeletal muscles),
increases when certain medicines are taken concomitantly (see section 2 "Mizetam with other medicines").
During treatment, the doctor will closely monitor the patient’s health if they have diabetes or are at risk of developing diabetes. The risk of developing diabetes is higher in people who have high levels of blood sugar and fats, are overweight, and have high blood pressure.
Inform your doctor about all medical conditions, including allergies.
Children and adolescents
Mizetam is not recommended for use in children and adolescents.
Mizetam with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Avoid taking Mizetam together with fibrates (medicines that lower cholesterol levels).
There are several medicines that may alter the effect of Mizetam, or whose effect may be altered by Mizetam (see section 3). This type of interaction may reduce the effectiveness of one or both medicines. It may also increase the risk or severity of adverse effects, including a serious condition damaging muscles known as "rhabdomyolysis", described in section 4:

• cyclosporine (a medicine often used in organ transplant patients).
• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (medicines used to treat bacterial infections).
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines used to treat fungal infections).
• gemfibrozil, other fibrates and fibric acid derivatives, nicotinic acid, colestipol, cholestyramine (medicines used to regulate fat levels).
• certain calcium channel blockers used for angina and high blood pressure, e.g. amlodipine, diltiazem.
• digoxin, verapamil, amiodarone (medicines regulating heart rhythm).
• medicines used to treat HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir with ritonavir (used in the treatment of AIDS).
• antiviral medicines used to treat hepatitis C virus infection, such as telaprevir, boceprevir, the combination of elbasvir and grazoprevir, letermovir when given with cyclosporine.
• if oral fusidic acid is required to treat a bacterial infection, the use of this medicine should be temporarily discontinued. The doctor will advise when it is safe to resume taking Mizetam. Taking Mizetam together with fusidic acid may rarely lead to muscle weakness, tenderness or pain (rhabdomyolysis). For further information about rhabdomyolysis, see section 4.
• Other medicines interacting with the combination product:
• oral contraceptives (medicines preventing pregnancy).
• stiripentol (an anticonvulsant used in the treatment of epilepsy).
• cimetidine (a medicine used to treat heartburn and stomach ulcers).
• phenazone (a pain-relieving medicine).
• antacids (products containing aluminium or magnesium).
• warfarin, phenprocoumon, acenocoumarol or fluindione (medicines used to prevent blood clots).
• colchicine (used in the treatment of gout).
• St John's wort Hypericum perforatum (a herbal remedy used to treat depression).

Mizetam with food and alcohol
See section 3 for instructions on how to take Mizetam. Please pay attention to the following:
Grapefruit juice
Do not exceed one or two small glasses of grapefruit juice per day, as larger quantities may alter the effect of Mizetam.
Alcohol
Avoid drinking excessive amounts of alcohol while being treated with this medicine. See section 2 "Warnings and precautions".
Pregnancy, breastfeeding and fertility
Do not take Mizetam if you are pregnant, planning to become pregnant, or suspect you may be pregnant.
Do not use Mizetam in women of childbearing age unless they are using effective contraception. If you become pregnant while taking Mizetam, you must stop taking the medicine immediately and inform your doctor without delay.
Do not take Mizetam while breastfeeding.
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before taking this medicine.
Driving and operating machinery
Mizetam is not expected to affect the ability to drive or operate machinery. However, bear in mind that dizziness may occur in some people after taking Mizetam. If dizziness occurs after taking this medicine, do not drive or operate machinery.
Mizetam contains lactose
If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
Mizetam contains sodium
Mizetam contains less than 1 mmol of sodium (23 mg) per tablet; this is considered essentially "sodium-free".

3. How to take Mizetam

This medicine should always be taken exactly as prescribed by the doctor. The doctor will determine the appropriate dose for each individual patient based on the current treatment and individual risk factors.
If in doubt, consult a doctor or pharmacist.

• Before starting treatment with Mizetam, a cholesterol-lowering diet should be initiated.
• During treatment with Mizetam, a cholesterol-lowering diet should be maintained.

How to dose Mizetam
The recommended dose of Mizetam is one tablet taken orally once daily, preferably at the same time each day. The tablet should be swallowed with an adequate amount of fluid (e.g. one glass of water).

When to take Mizetam
Mizetam can be taken at any time of the day, regardless of meals.
If your doctor has prescribed Mizetam together with another cholesterol-lowering medicine containing cholestyramine or another bile acid sequestrant, Mizetam should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking more Mizetam than prescribed
Contact your doctor or pharmacist immediately.
If you forget to take Mizetam
Do not take a double dose to make up for the missed dose. Take your usual dose of Mizetam at the usual time on the following day.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If the patient experiences any of the following serious adverse effects, they should
stop taking the medicine immediately and contact their doctor or go to the
emergency department of the nearest hospital and bring the medicine packaging
with them.

• Severe allergic reaction causing swelling of the face, tongue, or throat, which may cause severe breathing difficulties.
• Serious illness characterized by skin peeling and swelling, skin blisters, sores in the mouth, eyes, genital areas, fever, skin rash with pink-red spots, particularly on the palms or soles of the feet, possibly with blisters.
• Weakness, tenderness, pain, or rupture of muscles, or red-brown discoloration of urine, and particularly if associated with malaise or high fever—this may be due to muscle breakdown. This condition may be life-threatening and may lead to kidney disease.
• Lupus-like syndrome (including rash, joint disorders, and effects on blood cells).

Seek medical advice immediately if the patient experiences unexpected or
unusual bleeding or bruising, as this may indicate liver disorders.

Common (may occur in less than 1 in 10 patients):

• Nasal congestion, sore throat, nosebleeds,
• Allergic reactions,
• Increased blood glucose levels; in diabetic patients, blood glucose levels should be closely monitored,
• Headache,
• Nausea, constipation, flatulence, diarrhoea, indigestion, abdominal pain,
• Sore throat and (or) larynx,
• Joint pain and (or) pain in arms or legs, back pain, muscle pain, muscle cramps, joint swelling,
• Increased blood creatine kinase activity,
• Increased blood levels of liver enzymes AlAT and (or) AspAT,
• Feeling of fatigue,
• Blood test results indicating abnormal liver function.

Uncommon (may occur in less than 1 in 100 patients):

• Swelling due to allergic reaction,
• Decreased blood glucose levels (diabetic patients should closely monitor blood glucose levels),
• Loss of appetite, weight gain,
• Cough,
• Muscle weakness, neck pain, chest pain,
• Hot flushes, high blood pressure,
• Vomiting, regurgitation, pancreatitis and hepatitis, heartburn, gastritis, dry mouth,
• Skin redness, urticaria, skin rash and itching, hair loss,
• Nightmares, difficulty sleeping,
• Dizziness, numbness, disturbances in taste sensation, memory loss (amnesia), sensory disturbances,
• Blurred vision,
• Tinnitus (ringing in the ears),
• Feeling of general discomfort, restlessness or pain,
• Weakness,
• Increased blood activity of the liver enzyme gamma-glutamyl transferase,
• Presence of white blood cells in urine analysis.

Rare (may occur in less than 1 in 1,000 patients):

• Decreased platelet count,
• Swelling of deeper layers of skin in the face, tongue, throat, abdomen, arms or legs (angioedema),
• Extensive rash forming sharply demarcated red patches or rash with blisters and peeling skin, especially around the mouth, nose, eyes, and genital organs due to allergic reaction,
• Inflammation of skeletal muscles, tendon inflammation sometimes leading to tendon rupture, muscle weakness due to loss of muscle fibres,
• Visual disturbances,
• Yellowing of the skin and whites of the eyes (jaundice).

Very rare (may occur in less than 1 in 10,000 patients):

• Anaphylactic shock due to allergic reaction,
• Hearing loss,
• Liver failure,
• Breast enlargement in men.

Frequency not known (cannot be estimated from available data):

• Allergic reactions, including rash and swelling of deeper skin layers,
• Shortness of breath, inflammation of the gallbladder, gallstones,
• Physical weakness, loss of strength, loss of muscle tissue due to antibody activity,
• Depression,
• Myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing),
• Ocular myasthenia (a disease causing weakness of eye muscles). The patient should speak to their doctor if they experience weakness in arms or legs worsening after
  periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Additionally, following marketing authorization, the following adverse effects have been reported during the use of certain statins (cholesterol-lowering medicines):

• Breathing difficulties, including chronic cough and (or) shortness of breath or fever,
• Diabetes: the likelihood of occurrence depends on the presence or absence of risk factors (fasting glucose ≥5.6 mmol/l, BMI >20 kg/m², elevated triglyceride levels, history of hypertension),
• Depression,
• Sexual dysfunction.

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

5. How to store Mizetam

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of the stated month.
The marking on the packaging after the abbreviation "EXP" indicates the expiry date, and after the abbreviation "Lot" indicates the batch number.
Store in the original packaging to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Mizetam contains

• The active substances are ezetimibe and atorvastatin. Each tablet contains 10 mg of ezetimibe and 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin (as atorvastatin calcium trihydrate).
• Other ingredients are: lactose monohydrate, calcium carbonate, microcrystalline cellulose, sodium lauryl sulfate, sodium croscarmellose, povidone K30, hydroxypropylcellulose, magnesium stearate, polysorbate 80.

What Mizetam looks like and contents of the pack
Mizetam 10 mg + 10 mg: white or almost white capsule-shaped tablet (12.7 mm x 5.1 mm),
with engraved mark "1" on one side.
Mizetam 10 mg + 20 mg: white or almost white capsule-shaped tablet (14.5 mm x 6.8 mm),
with engraved mark "2" on one side.
Mizetam 10 mg + 40 mg: white or almost white capsule-shaped tablet (16.4 mm x 6.3 mm),
with engraved mark "3" on one side.
Mizetam 10 mg + 80 mg: white or almost white capsule-shaped tablet (17.0 mm x 8.0 mm),
with engraved mark "4" on one side.
Mizetam is available in packs of 10, 30, 90 and 100 tablets in OPA/Aluminium/PVC blisters
contained in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
Hennig Arzneimittel GmbH & Co. KG
Liebigstr. 1-2
65439 Flörsheim Am Main, Hessen
Germany

Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański