Tovastibe

PATIENT INFORMATION LEAFLET

Patient Information Leaflet: Information for the Patient

Tovastibe 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
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, because it could be harmful.
‐ If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or
pharmacist. See section 4.
Contents of this leaflet

1. What Tovastibe is and what it is used for

2. What you need to know before taking Tovastibe

3. How to take Tovastibe

4. Possible side effects

5. How to store Tovastibe

6. Contents of the pack and other information

7. What Tovastibe is and what it is used for

Tovastibe is a medicine used to reduce elevated cholesterol levels. Tovastibe contains
ezetimibe and atorvastatin.
Tovastibe is used in adults to reduce levels of total cholesterol, "bad" cholesterol
(LDL cholesterol), and blood fats called triglycerides. In addition, Tovastibe increases levels of "good"
cholesterol (HDL cholesterol).
Tovastibe works in two ways to reduce cholesterol. It reduces cholesterol absorbed in the digestive
tract as well as cholesterol naturally produced by the body.
Cholesterol is one of several fatty substances present in the bloodstream. Total cholesterol is
composed mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" 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 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 accumulating in
the arteries and provides protection against heart disease.
Triglycerides are another form of fat in the blood that can increase the risk of heart disease.
Your doctor may prescribe Tovastibe if you are already taking both atorvastatin and ezetimibe at the
same dose level as a substitute therapy, in addition to diet, to lower cholesterol if you have:
elevated blood cholesterol levels (primary hypercholesterolemia, heterozygous and homozygous familial and non-familial) or elevated blood fat levels (mixed hyperlipidemia).
Tovastibe does not help with weight loss.

2. What you need to know before taking Tovastibe

Do not take Tovastibe if

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Tovastibe if

• you have previously had a stroke with cerebral hemorrhage or if there are small accumulations of fluid in the brain due to previous strokes
• you have kidney problems
• you have an underactive thyroid gland (hypothyroidism)
• you have experienced repeated or unexplained episodes of muscle discomfort or pain, or have a personal or family history of muscle problems
• you have previously had muscle problems while being treated with other lipid-lowering medicines (e.g., other "statin" or "fibrate" medicines)
• 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).
• you regularly consume large amounts of alcohol
• you have a history of liver disease
• you are over 70 years old

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness
while taking Tovastibe. This is because muscle problems can, in rare cases, 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.
Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and medicines may be needed to diagnose and treat this condition.
Talk to your doctor or pharmacist before taking Tovastibe if

• you have severe respiratory insufficiency. If any of these conditions apply to you (or if you are unsure), talk to your doctor or pharmacist before taking Tovastibe, 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 side effects, such as rhabdomyolysis (breakdown of damaged skeletal muscle), increases when certain medicines are taken together (see section 2 “Other medicines and Tovastibe”).

If you have diabetes or are at risk of developing diabetes, your doctor will monitor you closely while you are taking this medicine. You are likely at 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.
Children
The use of Tovastibe is not recommended for children and adolescents.
Other medicines and Tovastibe
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
During treatment with Tovastibe, you should avoid taking fibrates (cholesterol-lowering medicines).
A medicine containing the active substances ledipasvir and sofosbuvir. This medicine is administered for the treatment of chronic (long-term) hepatitis C virus infection in adults and children aged 3 years and older.
Taking Tovastibe with this medicine may worsen side effects. Your doctor may need to prescribe a different medicine or adjust the dose of the medicine you are taking.
Some medicines can alter the effect of Tovastibe or their effect can be altered by Tovastibe (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, derivatives, colestipol, cholestyramine (medicines used to regulate lipid levels)
• some calcium antagonists used to treat angina or hypertension, e.g., amlodipine, diltiazem
• digoxin, verapamil, amiodarone (medicines used to regulate heart rhythm)
• letermovir, a medicine used to prevent cytomegalovirus disease
• medicines used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (medicines for treating AIDS)
• some 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 bacteremia).
• 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 Tovastibe. Taking Tovastibe together with fusidic acid can 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 for the treatment of 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). Tovastibe with food and alcohol See section 3 for instructions on how to take Tovastibe. 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 can alter the effects of the combination medicine. Alcohol Avoid drinking excessive amounts of alcohol while being treated with this medicine. See section 2 “Warnings and precautions” for further details.

Pregnancy, breastfeeding, and fertility
Do not take Tovastibe if you are pregnant, trying to become pregnant, or suspect you are pregnant.
Do not take Tovastibe if you are of childbearing age unless you are using a reliable method of contraception.
If you become pregnant while taking Tovastibe, stop treatment immediately and contact your doctor.
Do not take Tovastibe if you are breastfeeding.
If you are pregnant, suspect you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
Tovastibe is not expected to affect your ability to drive or operate machinery.
However, consider that some people may experience dizziness after taking Tovastibe.
Do not drive or operate machinery if you feel dizzy after taking this medicine.
Tovastibe contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Tovastibe contains sodium
Tovastibe contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

3. How to take Tovastibe

Always take this medicine exactly as your doctor has instructed. Your doctor will decide the appropriate tablet dosage for you based on your ongoing treatment and risk profile.
If you have any doubts, consult your doctor or pharmacist.

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

What dose to take
The recommended dose is one Tovastibe tablet once daily, preferably at the same time each day. The tablet should be swallowed with sufficient liquid (e.g., a glass of water).
When to take the dose
Take Tovastibe at any time of day. You may take it with or without food.
If your doctor has prescribed Tovastibe in combination with colestyramine or another bile acid sequestrant (medicines used to lower cholesterol), you must take Tovastibe at least 2 hours before or 4 hours after taking the bile acid sequestrant.
If you take more Tovastibe than you should
Contact your doctor or pharmacist.
If you forget to take Tovastibe
Do not take a double dose to make up for the forgotten tablet. Simply take your next dose at the usual time the following day.
If you have any doubts about how to use this medicine, contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 peeling and swelling of the skin, 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
• weakness, tenderness, pain, muscle strain 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 problems and effects on blood cells)

If you develop problems characterized by unexpected or unusual bleeding or bruising, consult your doctor promptly, as these may be signs of liver disorder.
Other possible side effects with Tovastibe
Common: (may affect up to 1 in 10 people)

• inflammation of the nasal cavity, 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
• increases in certain blood values related to muscle function (creatine kinase (CK))
• abnormal liver function tests, increases in certain blood values related to liver function (transaminases)
• feeling of fatigue

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, skin rash, itching
• hair loss
• nightmares, difficulty falling asleep
• dizziness
• numbness
• altered sense of taste
• amnesia
• abnormal local sensations
• blurred vision
• ringing in the ears
• general feeling of malaise, discomfort or pain
• weakness
• increase in the liver enzyme gamma-glutamyltransferase
• positive urine test for white blood cells

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

• reduction in blood platelets
• swelling of the subcutaneous layer of the face, tongue, throat, abdomen, arms or legs (angioneurotic oedema)
• widespread rash forming clearly defined red patches or rash with blisters and peeling, particularly around the mouth, nose, eyes and genitals, as a result of an allergic reaction
• inflammation of skeletal muscle, inflammation of tendons, 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)

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

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

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

• allergic reaction, including rash and swelling of the subcutaneous layers
• shortness of breath, inflammation of the gallbladder, gallstones
• physical weakness and loss of strength, loss of muscle tissue caused by 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: more likely if you have high levels of sugar and fats in the blood, are overweight and have high blood pressure. Your doctor will monitor you during treatment with this medicine
• sexual difficulties

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 Tovastibe

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. 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. Pack contents and other information

What Tovastibe contains
Tovastibe 10 mg/10 mg: each film-coated tablet contains 10 mg of ezetimibe and 10 mg of
atorvastatin (as calcium trihydrate).
Tovastibe 10 mg/20 mg: each film-coated tablet contains 10 mg of ezetimibe and 20 mg of
atorvastatin (as calcium trihydrate).
Tovastibe 10 mg/40 mg: each film-coated tablet contains 10 mg of ezetimibe and 40 mg of
atorvastatin (as calcium trihydrate).
Tovastibe 10 mg/80 mg: each film-coated tablet contains 10 mg of ezetimibe and 80 mg of
atorvastatin (as calcium trihydrate).

The other components are:
Tablet core:
microcrystalline cellulose 101 (E460), mannitol (E 421), calcium carbonate (E170), sodium croscarmellose
(E468), hydroxypropylcellulose (E463), polysorbate 80 (E433), yellow iron oxide (E172),
magnesium stearate (E470b), povidone K29/32 (E1201), sodium lauryl sulfate (E487).
Tablet coating
Tovastibe 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg - Opadry White OY-L-28900 composed of:
Lactose monohydrate
Hypromellose 2910 (E464)
Titanium dioxide (E171)
Macrogol 4000 (E1521)
Tovastibe 10 mg/80 mg - DrCoat FCU composed of:
Hypromellose 2910
Titanium dioxide (E171)
Talc (E 553b)
Macrogol 400
Yellow iron oxide (E172)

Description of the appearance of Tovastibe and pack contents
Tovastibe 10 mg/10 mg film-coated tablets: white, round, biconvex film-coated tablets with a diameter of approximately 8.1 mm
Tovastibe 10 mg/20 mg film-coated tablets: white, oval-shaped, biconvex film-coated tablets with dimensions of approximately 11.6 x 7.1 mm
Tovastibe 10 mg/40 mg film-coated tablets: white, capsule-shaped, biconvex film-coated tablets with dimensions of approximately 16.1 x 6.1 mm
Tovastibe 10 mg/80 mg film-coated tablets: yellow, oblong, biconvex film-coated tablets with dimensions of approximately 19.1 x 7.6 mm

Tovastibe 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg film-coated tablets
Blister packs OPA/Al/PVC//Al containing 10, 30, 90 and 100 film-coated tablets.
Tovastibe 10 mg/80 mg film-coated tablets
Blister packs OPA/Al/PVC//Al containing 10, 30 film-coated tablets, multiple pack containing 90 (2 packs of 45) and multiple pack containing 100 (2 packs of 50) film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder:
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart
Dublin 15
Dublin
Ireland

Manufacturers:
Elpen Pharmaceutical Co. Inc
Marathonos Ave. 95,
Pikermi Attiki, 19009
Greece
Lek Pharmaceuticals d.d.
Verovškova ulica 57,
Ljubljana, 1526,
Slovenia

This medicinal product is authorized in the European Economic Area Member States under the
following names:
Germany Tovastibe 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg, 10 mg/80 mg
Filmtabletten
Italy Tovastibe
Netherlands Tovastibe 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg, 10 mg/80 mg,
filmomhulde tabletten