Zentasta

Package leaflet: Information for the patient

Zentasta, 10 mg + 10 mg, tablets
Zentasta, 10 mg + 20 mg, tablets
Zentasta, 10 mg + 40 mg, tablets
Zentasta, 10 mg + 80 mg, tablets
Ezetimibum + Atorvastatinum
Please read this leaflet carefully before using the medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Zentasta is and what it is used for

Zentasta is a medicine that lowers high cholesterol levels. Zentasta contains ezetimibe and atorvastatin.
Zentasta is a medicine used in adults to reduce total cholesterol levels, including "bad" cholesterol (LDL cholesterol) and fat substances called triglycerides in the blood. In addition, Zentasta increases levels of "good" cholesterol (HDL cholesterol).
Zentasta 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, thereby 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.
Zentasta is used in patients in whom diet alone is not sufficient to control cholesterol levels. While taking this medicine, you should follow a cholesterol-lowering diet.
Your doctor may prescribe Zentasta if you are already taking both active substances—atorvastatin and ezetimibe—at the doses contained in this medicine.
Zentasta is used when patients have:

• elevated blood cholesterol levels (primary hypercholesterolemia) [heterozygous and homozygous familial and non-familial], or elevated blood fat levels (mixed hyperlipidemia).
• heart disease; Zentasta reduces the risk of heart attack, stroke, procedures to improve blood flow to the heart, or hospitalization due to chest pain.

Zentasta does not affect body weight reduction.

2. Important information before using Zentasta

When not to use Zentasta

• if the patient is allergic to ezetimibe, atorvastatin, 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/pibrentasvir for the treatment of hepatitis C
• if oral fusidic acid is required to treat a bacterial infection, the use of this medicine must be stopped immediately. The doctor will inform the patient when it is safe to restart taking Zentasta. Taking Zentasta with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). For additional information on rhabdomyolysis, see section 4.

Warnings and precautions
Before starting treatment with Zentasta, discuss with your doctor or pharmacist:

• if the patient previously had a haemorrhagic stroke or has small fluid-filled sacs in the brain following previous strokes
• if the patient has kidney disease
• if the patient has hypothyroidism (underactive thyroid)
• if the patient has recurrent or unexplained muscle pain, or if the patient has had muscle disease or if it occurred in the family
• if the patient is currently taking or has taken within the last 7 days a medicine called fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and a medicine containing ezetimibe and atorvastatin may lead to serious consequences, including muscle problems (rhabdomyolysis)
• if the patient previously experienced muscle-related symptoms during treatment with other lipid-lowering medicines (e.g. other "statins" or "fibrates")
• if the patient regularly consumes large amounts of alcohol
• if the patient previously had liver disease
• if the patient is over 70 years of age
• if the patient has severe respiratory insufficiency
• 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)

Contact your doctor immediately if you experience unexplained
muscle pain, tenderness, or weakness while taking this medicine. In rare
cases, muscle-related symptoms may be serious, including muscle breakdown leading to kidney damage.
If any of the situations listed above apply to the patient (or the patient is unsure), they should
consult their doctor or pharmacist before taking Zentasta, as the doctor may need to perform a blood test 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 (skeletal muscle breakdown),
increases when certain medicines are taken concomitantly (see section 2. "Zentasta and 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 development of diabetes is more likely in individuals with high blood sugar and fat levels, overweight, and high blood pressure.
A small number of people may experience effects of statins on the liver. This is detected by a simple test measuring elevated levels of liver enzymes in the blood. For this reason, the doctor will regularly perform this blood test (liver function test) during treatment with Zentasta. It is important to visit the doctor for laboratory test referrals.
Inform your doctor about all medical conditions, including allergies.

Children and adolescents
Zentasta is not recommended for use in children and adolescents.

Zentasta and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Avoid concomitant use of Zentasta with fibrates (medicines that lower cholesterol levels).
There are several medicines that may alter the effect of Zentasta or whose effect may be altered by Zentasta (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 (commonly used in organ transplant patients)
• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (used to treat bacterial infections)
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (used to treat fungal infections)
• gemfibrozil, other fibrates, nicotinic acid and derivatives, colestipol, cholestyramine (medicines used to regulate fat levels)
• certain calcium channel blockers used for angina and hypertension, e.g. amlodipine, diltiazem
• digoxin, verapamil, amiodarone (medicines regulating heart rhythm)
• letermovir (a medicine used to prevent cytomegalovirus disease)
• medicines used in the treatment of HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir with ritonavir (used in the treatment of AIDS)
• antiviral medicines used in the treatment of hepatitis C, such as telaprevir, boceprevir, and the combinations elbasvir/grazoprevir, ledipasvir/sofosbuvir
• if oral fusidic acid is required to treat a bacterial infection, temporary discontinuation of this medicine is necessary. The doctor will advise when it is safe to resume taking Zentasta. Taking Zentasta concomitantly with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). For additional information on rhabdomyolysis, see section 4.
• daptomycin (a medicine used to treat complicated skin and skin tissue infections and bloodstream infections caused by bacteria)
• Other medicines interacting with Zentasta
  • oral contraceptives (birth control medicines)
  • 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)

Zentasta with food and alcohol
See section 3 for information on how to take Zentasta. Pay attention to the following:
Grapefruit juice
Do not exceed one or two small glasses of grapefruit juice, as larger quantities may alter the effect of Zentasta.
Alcohol
Avoid consuming excessive amounts of alcohol while being treated with this medicine. See section 2. "Warnings and precautions".

Pregnancy, breastfeeding, and fertility
Do not use Zentasta if the patient is pregnant, planning to become pregnant, or suspects she may be pregnant.
Do not use Zentasta in women of childbearing age unless they are using effective methods of contraception. If a patient becomes pregnant while taking Zentasta, she must immediately stop taking the medicine and promptly inform her doctor.
Do not use Zentasta during breastfeeding.
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before taking this medicine.

Driving and operating machinery
Zentasta is not expected to affect the ability to drive or operate machinery. However, bear in mind that dizziness may occur in some individuals after taking Zentasta. If dizziness occurs after taking this medicine, do not drive or operate machinery.

Zentasta contains lactose and sodium
If the patient has been previously diagnosed with an intolerance to certain sugars, they should consult their doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, which essentially means it is "sodium-free".

3. How to use Zentasta

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

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

How to take Zentasta
The recommended dose of Zentasta 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 Zentasta
Zentasta can be taken at any time of the day. It may be taken independently of meals.
If your physician has prescribed Zentasta together with another cholesterol-lowering medicine containing the active substance cholestyramine or another bile acid sequestrant, Zentasta should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking more Zentasta than prescribed
Consult a physician or pharmacist.

If a dose of Zentasta is missed
Do not take a double dose to make up for the missed dose. Take the next dose at the usual time on the following day.

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

• Severe allergic reaction causing swelling of the face, tongue, and throat, which may cause severe breathing difficulties.

• Severe illness characterized by peeling and swelling of the skin, skin blisters, blisters in the mouth, eyes, genital area, fever, skin rash with pink-red spots, particularly on the palms or soles of the feet, possibly with blisters.

• Muscle weakness, tenderness, pain, muscle rupture, or red-brown discoloration of urine, and particularly if accompanied by malaise or high fever, which 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, which may indicate liver disorders.
Other possible adverse reactions of Zentasta:
Common: (may occur in up to 1 in 10 people)

• Nasal inflammation, sore throat, nosebleeds.
• Allergic reactions.
• Increased blood glucose levels; in diabetic patients, blood glucose levels should be closely monitored.
• Headaches.
• Nausea, constipation, flatulence, diarrhea, indigestion, abdominal pain.
• Sore throat and/or larynx.
• Joint pain and/or pain in hands or feet, 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 up to 1 in 100 people)

• Decreased blood glucose levels (diabetic patients should closely monitor blood glucose levels).
• Loss of appetite, weight gain.
• Cough.
• Muscle weakness, neck pain, chest pain, swelling especially in ankles, elevated body temperature.
• Hot flushes, high blood pressure.
• Vomiting, belching, pancreatitis and hepatitis, heartburn, inflammation of the stomach lining, dry mouth.
• Skin redness, rash, skin eruptions and itching, urticaria, hair loss.
• Nightmares, difficulty sleeping.
• Dizziness, numbness, memory loss (amnesia), disturbances in taste sensation, loss of memory, sensory disturbances.
• Blurred vision.
• Ringing in the ears.
• Feeling of general discomfort, unease, or pain.
• Weakness.
• Increased blood levels of the liver enzyme gamma-glutamyl transferase (GGT).
• Presence of white blood cells in urine analysis.

Rare: (may occur in up to 1 in 1,000 people)

• Decreased platelet count.
• Numbness, tingling, or burning sensation in hands or feet (peripheral neuropathy).
• Inflammation of skeletal muscles, tendon inflammation sometimes with tendon rupture, muscle weakness as a sign of loss of muscle fibers.
• Visual disturbances.
• Yellowing of the skin and whites of the eyes.
• Skin rash which may appear on the skin, or oral ulcers (lichenoid drug reaction).
• Purple skin lesions (symptoms of vasculitis).

Very rare: (may occur in up to 1 in 10,000 people)

• Anaphylactic shock due to an 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.
• Persistent muscle weakness.
• Myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing).
• Ocular myasthenia (a disease causing weakness of eye muscles).

Talk to a doctor if the patient experiences weakness in the arms or legs, worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing, or shortness of breath.
Additionally, since market introduction, the following adverse reactions 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 occurrence of diabetes is more likely if the patient has high levels of blood sugar and fats, is overweight, or has high blood pressure. During treatment with this medicine, the doctor will monitor the patient's condition.
• Depression.
• Sexual dysfunction.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring Adverse Reactions of Medicinal Products
of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C, 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 authorization holder or its representative
in Poland.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Zentasta

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and packaging after "EXP". The expiry date refers to the last day of the specified month.
Store in the original packaging to protect from light.
Medicines should 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 Zentasta Contains

• The active substances in this medicine 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).
• The other ingredients are: lactose monohydrate, calcium carbonate, microcrystalline cellulose, sodium lauryl sulfate, sodium croscarmellose, povidone K30, hydroxypropylcellulose, magnesium stearate, and polysorbate 80.

What Zentasta Looks Like and Contents of the Pack
Zentasta 10 mg + 10 mg are white or almost white, capsule-shaped tablets (12.7 mm x 5.1 mm)
with "1" embossed on one side.
Zentasta 10 mg + 20 mg are white or almost white, capsule-shaped tablets (14.5 mm x 5.8 mm)
with "2" embossed on one side.
Zentasta 10 mg + 40 mg are white or almost white, capsule-shaped tablets (16.4 mm x 6.3 mm)
with "3" embossed on one side.
Zentasta 10 mg + 80 mg are white or almost white, capsule-shaped tablets (17.0 mm x 8.0 mm)
with "4" embossed on one side.
The tablets are packed in blisters made of OPA/Aluminum/PVC foil, sealed with an aluminum foil, containing
10, 30, 90, or 100 tablets, in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.,
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer
Hennig Arzneimittel GmbH & Co. KG
Liebigstr. 1-2
65439 Flörsheim am Main
Germany
Bluepharma – Indústria Farmacêutica, S.A.
Sao Martinho do Bispo
3045–016 Coimbra
Portugal

This medicinal product has been authorised in the European Economic Area countries under the following names:
Czech Republic, Slovakia, Romania, Portugal: ZETOVAR
Estonia, Latvia, Lithuania: TORZELIP
Poland: ZENTASTA

For more detailed information about this medicine, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. +48 (22) 375 92 00