Athemibe

Package Leaflet: Information for the Patient

ATHEMIBE 10 mg/10 mg film-coated tablets, 10 mg/20 mg film-coated tablets, 10 mg/40 mg film-coated tablets, 10 mg/80 mg film-coated tablets

ezetimibe and atorvastatin
Equivalent medicine
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, consult 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, consult your doctor or pharmacist. See section 4.
  Contents of this leaflet:
  1. What ATHEMIBE is and what it is used for
  2. What you need to know before taking ATHEMIBE
  3. How to take ATHEMIBE
  4. Possible side effects
  5. How to store ATHEMIBE
  6. Contents of the pack and other information

1. What ATHEMIBE is and what it is used for

ATHEMIBE is a medicine used to lower elevated cholesterol levels. ATHEMIBE contains ezetimibe and atorvastatin.
ATHEMIBE is used in adults to reduce levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and blood fats called triglycerides. In addition, ATHEMIBE increases levels of "good" cholesterol (HDL cholesterol).
ATHEMIBE works in two ways to reduce cholesterol. It reduces cholesterol absorbed in the gastrointestinal tract as well as cholesterol produced by the body itself. Cholesterol is one of several types of fat circulating in the bloodstream. Total cholesterol consists mainly of LDL and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate 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. Such blockage of blood flow may 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.
ATHEMIBE is used for patients who cannot control their cholesterol levels through diet alone. You must follow a cholesterol-lowering diet while taking this medicine.
ATHEMIBE is used in addition to diet to lower cholesterol levels when:

• you have high cholesterol in the blood (primary hypercholesterolemia [heterozygous familial and non-familial]) or high levels of fats in the blood (mixed hyperlipidemia);
• cholesterol levels are not well controlled with a statin alone;
• you are undergoing treatment previously managed with separate statin and ezetimibe tablets;
• you have a hereditary condition (homozygous familial hypercholesterolemia) that increases cholesterol levels in the blood. You may also be receiving other treatments;
• you have heart disease. ATHEMIBE reduces the risk of heart attack, stroke, need for surgery to improve blood flow to the heart, or hospitalization due to chest pain. ATHEMIBE does not help with weight loss.

2. What you need to know before taking ATHEMIBE

Do not take ATHEMIBE if
a. you are allergic to ezetimibe, atorvastatin, or any of the other ingredients of this
medicine (listed in section 6),
b. you have or have ever had a liver disease,
c. you have had unexplained abnormal blood tests related to liver function,
d. you are a woman of childbearing potential and are not using a reliable contraceptive method,
e. you are pregnant, trying to become pregnant, or breastfeeding,
f. you are taking the combination of glecaprevir/pibrentasvir for the treatment of hepatitis C.

Warnings and precautions
Talk to your doctor or pharmacist before taking ATHEMIBE if
a. you have previously had a stroke with cerebral haemorrhage or have small pockets of fluid in the brain
due to previous strokes,
b. you have kidney problems,
c. you have an underactive thyroid (hypothyroidism),
d. you have had repeated or unexplained muscle pain, or have a personal or family history of muscle
problems,
e. you have previously experienced muscle problems during treatment with other lipid-lowering medicines
(e.g. other "statin" or "fibrate" medicines),
f. you regularly drink large amounts of alcohol,
g. you have a history of liver disease,
h. you are over 70 years old,
i. your doctor has told you that you have an intolerance to certain sugars. Contact your doctor before
taking this product,
j. you are taking or have taken within the last 7 days a medicine called fusidic acid (a medicine for bacterial infections), taken orally or by injection. The combination of fusidic acid and ATHEMIBE can cause serious muscle problems (rhabdomyolysis).
k. you suffer or have suffered from myasthenia (a disease causing general muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen the condition or trigger the onset of myasthenia (see section 4).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or
weakness while taking ATHEMIBE. This is because, in rare cases, muscle problems can be severe, including muscle breakdown leading to kidney damage. It is known that atorvastatin can cause muscle problems, and cases of muscle problems have also been reported with ezetimibe.
Also inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatment may be needed to diagnose and manage this condition.
Consult your doctor or pharmacist before taking ATHEMIBE:

• if you suffer from severe respiratory insufficiency.

If any of these conditions apply to you (or you are unsure), consult your doctor or pharmacist before
taking ATHEMIBE, as your doctor may need to perform a blood test before and possibly during treatment with ATHEMIBE to assess the risk of muscle-related side effects. It is known that the risk of muscle-related side effects, such as rhabdomyolysis, increases when certain medicines are taken concomitantly (see section 2 "Other medicines and ATHEMIBE").
While taking this medicine, your doctor will monitor you closely if you have diabetes or are at risk of developing diabetes. You may be at higher risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure. Inform your doctor about all your medical conditions, including allergies.
The combined use of ATHEMIBE and fibrates (medicines to lower cholesterol) should be avoided, as the combination of ATHEMIBE and fibrates has not been studied.

Children
ATHEMIBE is not recommended for children and adolescents.

Other medicines and ATHEMIBE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines may alter the effect of ATHEMIBE or their effect may be altered by ATHEMIBE (see section 3). Such interactions could make one or both medicines less effective. Alternatively, they could increase the risk or severity of side effects, including the serious condition of muscle breakdown known as "rhabdomyolysis" described in section 4:

• ciclosporin (a medicine often used in organ transplant patients),
• erythromycin, clarithromycin, telithromycin, fusidic acid**, rifampicin (medicines for bacterial infections),
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines for fungal infections),
• gemfibrozil, other fibrates, nicotinic acid and derivatives, colestipol, cholestyramine (medicines to regulate lipid levels),
• certain calcium channel blockers used for angina or hypertension, e.g., amlodipine, diltiazem,
• digoxin, verapamil, amiodarone (medicines to regulate heart rhythm),
• medicines used in the treatment of HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (medicines for AIDS), some medicines used in the treatment of hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir/grazoprevir, ledipasvir/sofosbuvir,
• letermovir, a medicine that helps prevent cytomegalovirus infection,
• daptomycin (a medicine used to treat complicated skin and skin structure infections and bacteremia).
  **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 ATHEMIBE. Taking ATHEMIBE with fusidic acid may rarely cause muscle weakness, tenderness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

Other medicines known to interact with ATHEMIBE

• oral contraceptives (medicines to prevent pregnancy),
• stiripentol (an anticonvulsant medicine for epilepsy),
• cimetidine (a medicine used for heartburn and peptic ulcers),
• phenazone (a painkiller),
• antacids (indigestion remedies 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).

ATHEMIBE with food and alcohol
See section 3 for instructions on how to take ATHEMIBE. Please note 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 ATHEMIBE.
Alcohol
Avoid drinking excessive amounts of alcohol while taking this medicine. See section 2 "Warnings and
precautions" for details.

Pregnancy and breastfeeding
Do not take ATHEMIBE if you are pregnant, trying to become pregnant, or think you might be pregnant. Do
not take ATHEMIBE if you are of childbearing potential unless you are using reliable contraceptive measures.
If you become pregnant while taking ATHEMIBE, stop taking it immediately and inform your doctor. Do not take ATHEMIBE if you are breastfeeding.
The safety of ATHEMIBE during pregnancy and breastfeeding has not yet been established. Ask your
doctor or pharmacist for advice before taking this medicine.

Driving and using machines
ATHEMIBE is not expected to affect your ability to drive or use machines.
However, you should be aware that some people may experience dizziness after taking ATHEMIBE.

ATHEMIBE contains lactose
ATHEMIBE tablets contain a sugar called lactose. If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.

ATHEMIBE contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially "sodium-free".

3. How to take ATHEMIBE

Always take this medicine exactly as your doctor has told you. Your doctor will determine
the appropriate tablet dosage for you, based on your current treatment and your individual
risk status. Consult your doctor or pharmacist if you are unsure.

• Before starting ATHEMIBE, you must follow a cholesterol-lowering diet.
• You must continue this cholesterol-lowering diet while taking ATHEMIBE.

How much to take
The recommended dose is one ATHEMIBE tablet taken orally once daily.

When to take it
Take ATHEMIBE at any time of day. You may take it with or without food.
If your doctor has prescribed ATHEMIBE together with colestyramine or any other bile acid sequestrant (cholesterol-lowering medicines), you must take ATHEMIBE at least 2 hours before or 4 hours after taking the bile acid sequestrant.

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

If you forget to take ATHEMIBE
Do not take a double dose; simply take your usual dose of ATHEMIBE at the regular time the next day.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, ATHEMIBE can cause adverse reactions, although not everyone experiences them.
If you experience any of the following serious adverse reactions or symptoms, stop taking the tablets
immediately and contact your doctor or go to the nearest hospital emergency department.

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

You must consult your doctor as soon as possible if you experience unexpected or unusual bleeding or bruising, as these may indicate liver problems.

The following common adverse reactions have been reported (may affect up to 1 in 10 people):

• diarrhea,
• muscle pain.

The following uncommon adverse reactions have been reported (may affect up to 1 in 100 people):

• influenza-like illness,
• depression; difficulty sleeping; sleep disturbances,
• dizziness; headache; tingling sensation,
• slow heart rate,
• hot flushes,
• shortness of breath,
• abdominal pain; abdominal distension; constipation; indigestion; flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; stomach ache,
• acne; urticaria,
• joint pain; back pain; leg cramps; muscle fatigue, spasms or weakness; pain in arms and legs,
• unusual weakness; feeling of tiredness or malaise; swelling, especially in the ankles (edema),
• increases in certain laboratory blood tests indicating liver or muscle dysfunction (CK),
• weight gain.

In addition, the following adverse reactions have been reported in people taking ezetimibe/atorvastatin tablets or ezetimibe or atorvastatin tablets alone:

• allergic reactions including swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing or swallowing (requiring immediate treatment),
• raised red skin rash, sometimes with target-like lesions,
• liver problems,
• cough,
• heartburn,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions including rash and urticaria,
• tendon injury,
• gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting),
• inflammation of the pancreas, often with severe abdominal pain,
• reduction in blood cell counts, which may cause bruising/bleeding (thrombocytopenia),
• nasal inflammation; nosebleeds,
• neck pain; pain; chest pain; throat pain,
• increases and decreases in blood sugar levels (if you have diabetes, you should continue to monitor your blood sugar levels closely),
• nightmares,
• numbness or tingling in fingers and toes,
• reduced sensitivity to pain or touch,
• altered sense of taste; dry mouth,
• memory loss,
• ringing in the ears and/or head; hearing loss,
• vomiting,
• belching,
• hair loss,
• increased body temperature,
• positive urine tests for white blood cells,
• blurred vision; visual disturbances,
• gynecomastia (breast enlargement in men),
• severe myasthenia (a disease causing general muscle weakness, including in some cases the muscles used for breathing),
• ocular myasthenia (a disease causing weakness of the eye muscles).

Talk to your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Possible side effects reported with some statins:

• sexual difficulties,
• depression,
• respiratory problems including persistent cough and/or shortness of breath or fever,
• diabetes. This is more likely if you have high levels of sugar and fat in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine,
• persistent muscle pain, tenderness or weakness, and particularly if, at the same time, you feel unwell or have a high temperature that does not resolve after stopping ATHEMIBE (frequency not known).

Reporting of adverse reactions
If you experience any adverse reaction, talk to your doctor or pharmacist. This includes any possible adverse reaction not listed in this leaflet. You can also report adverse reactions directly via the national reporting system at:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store ATHEMIBE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister or carton after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

What ATHEMIBE contains
The active substances are ezetimibe and atorvastatin. Each film-coated 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 calcium carbonate; anhydrous colloidal silica; sodium croscarmellose;
hydroxypropylcellulose; lactose monohydrate; povidone; magnesium stearate; microcrystalline cellulose;
polysorbate 80; sodium lauryl sulfate (E487).
The film coating contains: hypromellose, lactose monohydrate, titanium dioxide, macrogol, talc.

Description of the appearance of ATHEMIBE and package contents
Film-coated tablets, biconvex, capsule-shaped, white to almost white.
ATHEMIBE 10 mg/10 mg tablets: embossed on one side with "1T", smooth on the other side.
ATHEMIBE 10 mg/20 mg tablets: embossed on one side with "2T", smooth on the other side.
ATHEMIBE 10 mg/40 mg tablets: embossed on one side with "4T", smooth on the other side.
ATHEMIBE 10 mg/80 mg tablets: embossed on one side with "8T", smooth on the other side.

Pack sizes:
Blister Alu/AluA packs containing 10, 30, 90 and 100 film-coated tablets.
Not all pack sizes are marketed.

Marketing Authorization Holder
Piam Farmaceutici S.p.A.
Via XII Ottobre, 10
16121 - Genova
Italy

Manufacturer
Delorbis Pharmaceuticals Ltd
17 Athinon Street
Ergates Industrial Area
2643 Ergates Lefkosia
Cyprus

This medicinal product is authorized in the European Economic Area member states under the following names:
Ezetimibe/atorvastatin Axunio (NL)
Athemibe (IT)