Package Leaflet: Information for the User

ORVATEZ 10mg/20mg film-coated tablets

ORVATEZ 10mg/40mg film-coated tablets

ORVATEZ 10mg/80mg film-coated tablets

ezetimiba/atorvastatina

(ezetimibe/atorvastatin)

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as 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 pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See Section 4.

6. Contents of the pack and additional information

ORVATEZ is a medication that decreases high levels of cholesterol. ORVATEZ contains ezetimiba and atorvastatina.

ORVATEZ is used in adults to decrease levels of total cholesterol, "bad" cholesterol (low-density lipoprotein or LDL cholesterol), andother types of fatty substances called triglycerides that circulate in the blood.Additionally, ORVATEZincreases concentrations of "good" cholesterol (high-density lipoprotein or HDL).

ORVATEZacts by reducing cholesterol in two ways. It reduces the cholesterol absorbed in the digestive tract, as well as the cholesterol that your body produces on its own.

Cholesterol is one of the fatty substances that are found in the circulatory system.Serum cholesterol is composed mainly of LDL and HDL.

LDL cholesterol is often referred to as "bad" cholesterol because it can accumulate in the walls of your arteries, forming plaques. Over time, this accumulation of plaque can cause a narrowing of the arteries. This narrowing can make blood flow to vital organs such as the heart and brain slower or interrupted. This interruption of blood flow can trigger a myocardial infarction or a stroke.

HDL cholesterol is often referred to as "good" cholesterol because it helps to prevent bad cholesterol from accumulating in the arteries and protects them from cardiovascular diseases.

Triglycerides are another type of fat present in your blood that can increase the risk of cardiovascular disease.

ORVATEZis used in patients who cannot control their cholesterol levels solely with diet. While taking this medication, you should follow a cholesterol-lowering diet.

ORVATEZis used, along with a cholesterol-lowering diet,if you have:

• elevated levels of cholesterol in the blood (primary hypercholesterolemia [familial heterozygous and non-familial]) or elevated levels of fatty substances (mixed hyperlipidemia):
• • that are not well controlled with a statin alone
  • for which a statin and ezetimiba in separate tablets have been used

• a genetic disorder (familial hypercholesterolemia), which increases the level of cholesterol in the blood. You may also receive other treatments.

• cardiovascular disease,ORVATEZreduces the risk of myocardial infarction, stroke, coronary artery bypass grafting, or hospitalization for chest pain.

ORVATEZdoes not help you lose weight.

Do not take ORVATEZ

• if you are allergic to ezetimibe, atorvastatin, or any of the other ingredients of this medicine (listed in section 6),
• if you have or have had any liver disease,
• if you have had any unexplained abnormal results in liver function blood tests,
• if you are a woman of childbearing potential and are not using reliable contraceptive methods,

• if you are pregnant, trying to become pregnant, or breastfeeding,

• if you are taking the combination of glecaprevir/pibrentasvir for the treatment of hepatitis C.

Warnings and precautions

Consult your doctor or pharmacist before starting to take ORVATEZ.

• if you have had a previous stroke with intracranial hemorrhage, or have small fluid accumulations in the brain due to previous strokes,
• if you have kidney problems,
• if your thyroid gland has low activity (hypothyroidism),
• if you have had recurrent or unexplained muscle pain or discomfort, or a personal or family history of muscle problems,
• if you have experienced muscle problems during previous treatment with other lipid-lowering medicines (e.g., other medicines containing "statins" or "fibrates"),
• if you regularly consume large amounts of alcohol,
• if you have a history of liver disease,
• if you are over 70 years old,
• if your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine,

• if you are taking or have taken in the last 7 days a medicine that contains fusidic acid (used to treat bacterial infections) by mouth or injection. The combination of fusidic acid and ORVATEZ may cause severe muscle problems (rhabdomyolysis),

• if you have or have had myasthenia (a disease that causes generalized muscle weakness, which in some cases affects the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins may sometimes worsen the disease or cause myasthenia (see section 4).

Contact your doctor as soon as possible if you experience unexplained muscle pain, sensitivity, or muscle weakness while taking ORVATEZ.This is because, in rare cases, muscle problems can be severe, including muscle rupture causing kidney damage.Ezetimibe and atorvastatin have been reported to cause muscle problems.

Also inform your doctor or pharmacist if you experience persistent muscle weakness. Further tests and additional medicines may be needed to diagnose and treat this problem.

Consult your doctor or pharmacist before starting to take ORVATEZ:

• if you have severe respiratory failure.

If you are in any of the above circumstances (or are unsure), consult your doctor before starting to take ORVATEZ, as your doctor will need to perform a blood test before starting your treatment with ORVATEZ, and possibly during it, to predict the risk of experiencing muscle adverse effects. It is known that the risk of experiencing muscle adverse effects, e.g., rhabdomyolysis, increases when certain medicines are taken simultaneously (see section 2 “Taking ORVATEZ with other medicines”).

While you are taking this medicine, your doctor will monitor whether you have diabetes or are at risk of developing diabetes. This risk of diabetes increases if you have high levels of sugar and fat in your blood, obesity, and high blood pressure.

Inform your doctor of all your medical problems, including allergies.

Combining ORVATEZ with fibrates (certain lipid-lowering medicines) should be avoided, as the combination has not been studied.

Children

ORVATEZ is not recommended for children and adolescents.

Taking ORVATEZ with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine, including over-the-counter medicines.

There are some medicines that may modify the effect of ORVATEZ or whose effects may be affected by ORVATEZ (see section 3). This type of interaction could reduce the effectiveness of one or both medicines. On the other hand, it could also increase the risk or severity of adverse effects, including a severe condition in which muscle is destroyed, known as “rhabdomyolysis”, which is described in section 4:

• ciclosporin (a medicine often used in 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, nicotinic acid derivatives, colestipol, cholestyramine (medicines used to regulate lipid levels),
• some calcium channel blockers used to treat angina or high blood pressure, e.g., amlodipine, diltiazem,
• digoxin, verapamil, amiodarone (medicines that regulate heart rhythm),
• medicines used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (used to treat 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 fusidic acid orally to treat a bacterial infection, you will need to temporarily stop taking this medicine. Your doctor will tell you when you can restart treatment with ORVATEZ. The use of ORVATEZ with fusidic acid rarely may cause muscle weakness, sensitivity, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4

• Other medicines that are known to interact with ORVATEZ
• • oral contraceptives (medicines that prevent pregnancy),
  • estiripentol (an anticonvulsant medicine used to treat epilepsy),
  • cimetidine (a medicine used to treat stomach acid and ulcers),
  • phenazone (an analgesic),
  • antacids (products used to treat indigestion that contain aluminum or magnesium),
  • warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines that prevent blood clotting),
  • colchicine (used to treat gout),
  • St. John's Wort (a medicine used to treat depression).

Taking ORVATEZ with food and alcohol

See section 3 for instructions on how to take ORVATEZ. Please note the following:

Orange juice

Do not take more than one or two small glasses of orange juice per day, as large amounts of orange juice may alter the effects of ORVATEZ.

Alcohol

Avoid excessive alcohol consumption while taking this medicine. For more details, see section 2 “Warnings and precautions”.

Pregnancy and breastfeeding

Do not take ORVATEZ if you are pregnant, trying to become pregnant, or breastfeeding.

Do not take ORVATEZ if you can become pregnant, unless you are using reliable contraceptive methods. If you become pregnant while taking ORVATEZ, stop taking it immediately and inform your doctor.

Do not take ORVATEZ if you are breastfeeding.

ORVATEZ has not been proven to be safe during pregnancy and breastfeeding.

Consult your doctor or pharmacist before taking this medicine.

Driving and operating machines

ORVATEZ is not expected to interfere with your ability to drive or operate machines. However, some people may experience dizziness after taking ORVATEZ.

ORVATEZ contains lactose

ORVATEZ tablets contain a sugar called lactose. If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

ORVATEZ contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor. Your doctor will determine the appropriate dose per tablet for you, depending on your current treatment and personal risk situation. In case of doubt, consult your doctor or pharmacist again.

• Before starting to take ORVATEZ, you must be following a diet to reduce cholesterol.
• You will need to continue with this cholesterol-reducing diet while taking ORVATEZ.

How much to take

The recommended dose is one ORVATEZ tablet once a day taken orally.

Administration form

Take ORVATEZ at any time of the day. You can take it with or without food.

If your doctor has prescribed ORVATEZ along with cholestyramine or any other bile acid sequestrant (medications that reduce cholesterol levels), you must take ORVATEZ at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more ORVATEZ than you should

Consult your doctor or pharmacist.

If you forgot to take ORVATEZ

Do not take an extra dose; the next day, take your normal amount of ORVATEZ at the usual time.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If you experience any of the following serious side effects or symptoms, stop taking your tablets and immediately inform your doctor, or go to the nearest hospital emergency department.

• Severe allergic reactions that cause swelling of the face, tongue, and throat and may cause difficulty breathing

• Severe disease whose symptoms are intense peeling and skin inflammation, blistering on the skin, mouth, eyes, genitals, and fever; skin rash with pink or red spots, especially on the palms of the hands or soles of the feet, which may lead to blistering

• Weakness, sensitivity, pain, or muscle rupture, or a change in urine color to brown-red, and especially if it occurs at the same time, a feeling of discomfort or high temperature that may be caused by abnormal muscle destruction that may be potentially fatal and trigger kidney problems

• Lupus-like syndrome (including rash, joint disorders, and effects on blood cells)

Consult your doctor as soon as possible if you experience problems associated with the unexpected or unusual appearance of bleeding or bruising, as this may be indicative of liver disease.

The following side effects were frequently reported (may affect up to 1 in 10 patients):

• Diarrhea,
• Muscle pain.

The following side effects were infrequently reported (may affect up to 1 in 100 patients):

• Flu,
• Depression; sleep disorders; sleep disturbances,
• Dizziness; headache; tingling sensation,
• Slow heart rate,
• Angina,
• Shortness of breath,
• Abdominal pain; abdominal swelling; constipation; indigestion; flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; stomach upset,
• Acne; hives,
• Joint pain; back pain; muscle cramps in the legs; muscle fatigue, spasms, or weakness; pain in the arms and legs,
• Unusual weakness; feeling of fatigue or discomfort; inflammation, especially in the ankles (edema),
• Increased levels of some liver or muscle function tests (CK) in laboratory blood tests,
• Weight gain.

The following side effects were reported with an unknown frequency (the frequency cannot be estimated from the available data):

• Myasthenia gravis (a disease that causes generalized muscle weakness that, in some cases, affects the muscles used for breathing),
• Myasthenia ocular (a disease that causes weakness of the eye muscles).

Consult your doctor if you experience weakness in the arms or legs that worsens after periods of activity, double vision, or eyelid drooping, difficulty swallowing, or difficulty breathing.

In addition, the following side effects have been reported in people taking ORVATEZ tablets, ezetimibe, or atorvastatin:

• Allergic reactions that include facial inflammation, lip, tongue, and/or throat inflammation that may cause difficulty breathing or swallowing (which requires immediate medical treatment),
• Red skin rash and, in some cases, in the shape of a target,
• Liver problems,
• Cough,
• Heartburn,
• Loss of appetite; lack of appetite,
• High blood pressure,
• Itchy skin rash and allergic reactions that include the appearance of skin rash and hives,
• Tendon injury,
• Bile stones or inflammation of the gallbladder (which may cause abdominal pain, nausea, or vomiting),
• Pancreatitis, often accompanied by severe abdominal pain,
• Decreased blood cell count, which may cause bruising or bleeding (thrombocytopenia),
• Nasal congestion; nasal bleeding,
• Neck pain; chest pain; throat pain,
• Increased or decreased blood sugar levels (if you have diabetes, you should closely monitor your blood glucose levels),
• Nightmares,
• Numbness or tingling in the fingers of the hands and feet,
• Decreased sensitivity to pain or touch,
• Alteration of the sense of taste; dry mouth,
• Memory loss,
• Ringing in the ears and/or head; hearing loss,
• Vomiting,
• Belching,
• Hair loss,
• High temperature,
• Presence of white blood cells in urine tests,
• Blurred vision; visual disturbances,
• Gynecomastia (breast enlargement in men).

Possible side effects reported with some statins

• Sexual dysfunction,
• Depression,
• Respiratory problems, including persistent cough and/or shortness of breath or fever,
• Diabetes. It is more likely if you have high blood sugar and fat levels, obesity, and high blood pressure. Your doctor will monitor you while taking this medication,
• Constant muscle pain, sensitivity, or weakness, and especially if it occurs at the same time, a feeling of discomfort or high temperature that may not disappear after stopping treatment with ORVATEZ (unknown frequency).

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging or on the container after “CAD” or “EXP”. The expiration date is the last day of the month indicated.
• Store in the original packaging to protect it from oxygen.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE collection point at the pharmacy.Ask your pharmacist how to dispose of the containers and medications you no longer need if you are unsure. By doing so, you will help protect the environment.

Composition of ORVATEZ

The active principles are ezetimiba and atorvastatina. Each film-coated tablet contains 10mg of ezetimiba and 20mg, 40mg or 80mg of atorvastatina (as atorvastatina calcium trihydrate).

The other components are: calcium carbonate;colloidal anhydrous silica; sodium croscarmellose; hydroxypropylcellulose; lactose monohydrate; magnesium stearate; microcrystalline cellulose; polisorbate 80; povidone; sodium lauryl sulfate.

The coating of the tablet contains: hypromellose, macrogol 8000, titanium dioxide (E-171) and talc.

Appearance of the product and contents of the package

Film-coated tablets, capsule-shaped, biconvex and white to bone-colored.

ORVATEZ 10mg/20mg tablets: with the code “333” on one face

ORVATEZ 10mg/40mg tablets: with the code “337” on one face

ORVATEZ 10mg/80mg tablets: with the code “357” on one face

Package sizes:

Blister packs of 10, 30, 90 and 100 film-coated tablets in aluminium/aluminium (oriented polyamide-aluminium-PVC with aluminium coating).

Unit dose packs of 30 x 1 and 45 x 1 film-coated tablets in aluminium/aluminium (oriented polyamide-aluminium-PVC with aluminium coating).

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Phone: 915911279

Manufacturer:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Organon Heist bv

Industriepark 30

2220 Heist-op-den-Berg

Belgium

Local representative:

Laboratorios Farmacéuticos ROVI, S.A.

Julián Camarillo, 35 – 28037 Madrid

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names:

ORVATEZ:Germany, Greece, Italy, Portugal and Spain

TIOBLIS:Belgiumand Luxembourg

Date of the last review of this leaflet:07/2023.

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es