Ezevast

PATIENT INFORMATION LEAFLET: Information for the user

EZEVAST 10 mg/10 mg tablets, 10 mg/20 mg tablets, 10 mg/40 mg tablets, 10 mg/80 mg tablets

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

1. What Ezevast is and what it is used for

Ezevast is a medicine used to lower elevated cholesterol levels.
Ezevast contains ezetimibe and atorvastatin.
Ezevast is used in adults to lower levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fats called triglycerides in the blood. In addition, Ezevast increases levels of "good" cholesterol (HDL cholesterol).
Ezevast works in two ways to reduce cholesterol. It reduces the cholesterol absorbed in the digestive tract as well as the cholesterol naturally produced by the body.
Cholesterol is one of several fatty substances present in the bloodstream. Total cholesterol is made up mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" 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. Blocked blood flow can cause a heart attack or stroke.
HDL cholesterol is often called "good" because it helps prevent bad cholesterol from building up in the arteries and provides protection against heart disease.
Triglycerides are another type of fat in the blood that may increase the risk of heart disease.
Ezevast is used for patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
Your doctor may prescribe Ezevast to you if you are already taking both atorvastatin and ezetimibe at the same dose levels.
Ezevast does not help with weight loss.

2. What you need to know before taking Ezevast

Do not take Ezevast

• if you are allergic to atorvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6)
• if you have or have ever had liver disease
• if you have had unexplained abnormal blood tests assessing liver function
• if you are a woman of childbearing age and are not using a reliable contraceptive method
• if you are pregnant, trying to become pregnant, or breastfeeding
• if you are taking the combination drug glecaprevir/pibrentasvir for the treatment of hepatitis C

Warnings and precautions
Talk to your doctor or pharmacist before taking Ezevast

• if you have previously had a stroke with cerebral haemorrhage or if there are small accumulations of fluid in the brain due to previous strokes
• if you have kidney problems
• if you have an underactive thyroid gland (hypothyroidism)
• if you have experienced repeated or unexplained episodes of muscle discomfort or pain, or have a personal or family history of muscle disorders
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, which in some cases may include muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen myasthenia or trigger its onset (see section 4)
• if you have previously experienced muscle problems during treatment with other lipid-lowering medicines (e.g. other "statin" or "fibrate" medicines)
• if you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine for bacterial infection). The combination of fusidic acid and medicines containing atorvastatin/ezetimibe can cause serious muscle problems (rhabdomyolysis).
• if you regularly consume large amounts of alcohol
• if you have a history of liver disease
• if you are over 70 years of age

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness
while taking Ezevast. This is because, although rarely, muscle problems can be severe,
including muscle breakdown leading to kidney damage.
Talk to your doctor or pharmacist before taking Ezevast

• if you have severe respiratory failure.

If any of these conditions apply to you (or if you are unsure), consult your doctor or pharmacist before
taking Ezevast, as your doctor may ask you to have a blood test before and possibly during treatment to assess the risk of muscle-related side effects. It is known that
the risk of muscle-related adverse effects, for example rhabdomyolysis (breakdown of damaged skeletal muscle),
increases when certain medicines are taken concomitantly (see section 2 “Other medicines and Ezevast”).
If you have diabetes or are at risk of developing diabetes, your doctor will monitor you closely
during treatment with this medicine. You are probably at risk of developing diabetes if you have
high levels of sugar and fat in your blood, are overweight, and have high blood pressure.
Inform your doctor about all your medical conditions, including allergies.
Children and adolescents
The use of Ezevast is not recommended in children and adolescents.
Other medicines and Ezevast
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any
other medicine.
During treatment with Ezevast, the use of fibrates (medicines to lower cholesterol) should be avoided.
Some medicines may alter the effect of Ezevast or their effect may be altered by
Ezevast (see section 3). This type of interaction could reduce the effectiveness of one or both medicines. Alternatively, it could increase the risk or severity of adverse effects, including the serious condition of muscle breakdown known as “rhabdomyolysis”, described in section 4:

• cyclosporine (a medicine often used in organ transplant patients)

• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (medicines used for bacterial infections)

• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines used for fungal infections)

• gemfibrozil, other fibrates, nicotinic acid and derivatives, colestipol, cholestyramine (medicines used to regulate lipid levels)

• certain calcium antagonists used to treat angina or hypertension, e.g. amlodipine, diltiazem

• digoxin, verapamil, amiodarone (medicines used to regulate heart rhythm)

• medicines used to treat HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (medicines for the treatment of AIDS)

• certain medicines used to treat hepatitis C, e.g. telaprevir, boceprevir, and the combination of elbasvir/grazoprevir

• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bloodstream infections)

• If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when it is safe to restart Ezevast. Taking Ezevast together with fusidic acid may cause rare cases of muscle weakness, tenderness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

• Other medicines known to interact with the combination product:

  • oral contraceptives (medicines to prevent pregnancy)
  • stiripentol (an anticonvulsant medicine used to treat epilepsy)
  • cimetidine (a medicine used to treat heartburn and peptic ulcers)
  • phenazone (a painkiller)
  • antacids (medicines for digestive problems containing aluminium or magnesium)
  • warfarin, phenprocoumon, acenocoumarol or fluindione (medicines to prevent blood clots)
  • colchicine (used to treat gout)
  • St John’s wort (a herbal medicine used to treat depression)

Ezevast with food, drinks and alcohol
See section 3 for instructions on how to take Ezevast. Pay attention to the following:
Grapefruit juice
Do not drink more than one or two small glasses of grapefruit juice per day, as large quantities of grapefruit juice may alter the effects of the combination medicine.
Alcohol
Avoid drinking excessive amounts of alcohol during treatment with this medicine. See section 2 “Warnings and precautions” for further details.
Pregnancy, breastfeeding and fertility
Do not take Ezevast if you are pregnant, trying to become pregnant, or suspect you may be pregnant.
Do not take Ezevast if you are of childbearing age unless you are using a reliable contraceptive method. If you become pregnant while taking Ezevast, stop treatment immediately and consult your doctor.
Do not take Ezevast if you are breastfeeding.
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Ezevast is not considered to affect the ability to drive or operate machinery. However,
you should consider that some people may experience dizziness after taking Ezevast. Do not drive or operate machinery if you feel dizzy after taking this medicine.
Ezevast contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Ezevast contains sodium
Ezevast contains less than 1 mmol of sodium (23 mg) per tablet and is therefore essentially ‘sodium-free’.

3. How to take Ezevast

Take this medicine exactly as instructed by your doctor. Your doctor will determine the appropriate tablet dosage for you based on your ongoing treatment and individual risk profile. If you have any doubts, consult your doctor or pharmacist.

• Before starting to take Ezevast, you must have already begun a cholesterol-lowering diet.
• While taking Ezevast, you must continue to follow a cholesterol-lowering diet.

What dose to take
The recommended dose is one Ezevast tablet once daily, preferably at the same time each day. The tablet should be swallowed with an adequate amount of liquid (e.g. a glass of water).

When to take the dose
Take Ezevast at any time of day. It can be taken with or without food.
If your doctor has prescribed Ezevast together with colestyramine or another bile acid sequestrant (medicines used to lower cholesterol), you must take Ezevast at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezevast than you should
Contact your doctor or pharmacist.

If you forget to take Ezevast
Do not take a double dose to make up for the missed tablet. Simply take your next dose at the usual time the following day.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you notice any of the following serious side effects or symptoms, stop taking the tablets immediately and contact your doctor or go to the nearest hospital emergency department, taking the tablets with you:

• severe allergic reaction causing swelling of the face, tongue and throat, which may cause severe breathing difficulties
• severe illness with extensive skin peeling and swelling, blistering of the skin, mouth, eyes, genitals, and fever; skin rash with pink-red pustules, particularly on the palms of the hands or soles of the feet, which may develop into blisters
• muscle weakness, tenderness, pain, muscle tearing, or red-brown discoloration of the urine; especially if you also feel unwell and have a high fever, this may be due to abnormal muscle breakdown, which can be life-threatening and may lead to kidney problems
• lupus-like syndrome (including skin rash, joint disorders, and effects on blood cells)

If you develop symptoms of unusual or unexpected bleeding or bruising, consult your doctor as soon as possible, as these may be signs of liver disorder.
Other possible side effects with Ezevast

Common: (may affect up to 1 in 10 people)

• inflammation of the nasal passages, sore throat, nosebleeds
• allergic reactions
• increased blood glucose levels: diabetic patients should monitor their blood glucose levels
• headache
• nausea, constipation, flatulence, diarrhoea, indigestion, abdominal pain
• pain in the pharynx and/or larynx
• joint pain and/or pain in hands or feet, back pain, muscle pain (myalgia), muscle spasm, joint swelling
• increased blood creatine phosphokinase
• increased liver enzymes ALT and/or AST
• feeling of fatigue
• abnormal liver function test

Uncommon: (may affect up to 1 in 100 people)

• swelling due to allergic reactions
• decreased blood glucose levels: diabetic patients should monitor their blood glucose levels
• loss of appetite, weight gain
• cough
• muscle weakness, neck pain, chest pain
• hot flushes, hypertension
• vomiting, belching, inflammation of the pancreas and liver, heartburn, inflammation of the stomach lining, dry mouth
• skin redness, urticaria, rash, itching, hair loss
• nightmares, difficulty falling asleep
• dizziness, numbness, altered sense of taste, amnesia, localized abnormal sensations
• blurred vision
• ringing in the ears (tinnitus)
• general feeling of malaise, discomfort or pain
• weakness
• increased liver enzyme gamma-glutamyltransferase
• positive urine test for white blood cells

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

• reduced platelet count in the blood
• swelling of the subcutaneous layer of the face, tongue, throat, abdomen, arms or legs (angioedema)
• widespread rash with clearly defined red patches, or rash with blisters and skin peeling, particularly around the mouth, nose, eyes and genitals, due to an allergic reaction
• inflammation of skeletal muscle, tendon inflammation, sometimes complicated by rupture, muscle weakness due to loss of skeletal muscle fibres
• visual disturbances
• yellowing of the skin and whites of the eyes (jaundice)
• skin rash or mouth ulcers (drug-induced lichenoid reaction)
• purple skin lesions (signs of blood vessel inflammation, vasculitis)

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

• anaphylactic shock due to allergic reaction
• hearing loss
• liver failure
• breast enlargement in men (gynaecomastia)

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

• allergic reaction, including rash and swelling of subcutaneous layers
• shortness of breath, inflammation of the gallbladder, gallstones
• physical weakness and loss of strength, loss of muscle tissue due to autoimmune antibodies
• depression

In addition, the following side effects have been reported during the post-marketing phase for some statins (medicines used to lower cholesterol):

• breathing problems, including persistent cough and/or shortness of breath or fever
• diabetes: frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI > 30 kg/m², elevated triglycerides, history of hypertension)
• depression
• sexual difficulties
• 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.

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 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 Ezevast

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after "Exp.". The expiry date refers to the last day of that month.
Store in the original packaging to protect the product from light.
Do not dispose of any medicine 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 Ezevast 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).
• The other excipients are: monohydrate lactose, calcium carbonate, microcrystalline cellulose, sodium lauryl sulfate [E 487], sodium croscarmellose, povidone K30, hydroxypropylcellulose, magnesium stearate, and polysorbate 80.

Description of the appearance of Ezevast and contents of the pack
Ezevast 10 mg/10 mg tablets: capsule-shaped tablets, white to off-white in colour
(12.7 mm × 5.1 mm) with "1" engraved on one side
Ezevast 10 mg/20 mg tablets: capsule-shaped tablets, white to off-white in colour
(14.5 mm × 5.8 mm) with "2" engraved on one side
Ezevast 10 mg/40 mg tablets: capsule-shaped tablets, white to off-white in colour
(16.4 mm × 6.3 mm) with "3" engraved on one side
Ezevast 10 mg/80 mg tablets: capsule-shaped tablets, white to off-white in colour
(17.0 mm × 8.0 mm) with "4" engraved on one side
Pack sizes of 10, 30, 90, and 100 tablets in blisters of OPA/aluminum/PVC, contained in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Fidia Farmaceutici S.p.A.
Via Ponte della Fabbrica 3/A
35031 Abano Terme
Italy

Manufacturer
Hennig Arzneimittel GmbH & Co. KG
Liebigstraße 1-2
65439 Flörsheim am Main, Hessen
Germany
Bluepharma Indústria Farmacêutica, S.A.
São Martinho do Bispo
3045-016 Coimbra
Portugal
Zakłady Farmaceutyczne Polpharma S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
Poland

This medicinal product is authorized in the European Economic Area countries under the following
names:
Netherlands: EZEVAST 10 mg/ 10 mg, 20 mg, 40 mg, 80 mg, tabletten
Italy: EZEVAST 10 mg/ 10 mg, 20 mg, 40 mg, 80 mg, compresse