ORVATEZ 10 MG/40 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

ORVATEZ 10mg/20mg film-coated tablets

ORVATEZ 10mg/40mg film-coated tablets

ORVATEZ 10mg/80mg film-coated tablets

ezetimibe/atorvastatin

(ezetimibe/atorvastatin)

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is ORVATEZ and what is it used for
2. What you need to know before you take ORVATEZ
3. How to take ORVATEZ
4. Possible side effects
5. Storage of ORVATEZ

1. Contents of the pack and other information

1. What is ORVATEZ and what is it used for

ORVATEZ is a medicine that lowers high cholesterol levels. ORVATEZ contains ezetimibe and atorvastatin.

ORVATEZ is used in adults to lower the levels of total cholesterol, "bad" cholesterol (LDL cholesterol) and substances called triglycerides in the blood. It also raises the levels of "good" cholesterol (HDL cholesterol).

ORVATEZ works by reducing cholesterol in two ways. It reduces the amount of cholesterol absorbed in the gut and the amount of cholesterol produced by the body.

Cholesterol is one of the fatty substances that can be found in the blood. Your total cholesterol level is made up mainly of LDL and HDL cholesterol.

LDL cholesterol is often called "bad" cholesterol because it can build up in the walls of your arteries, forming plaques. Over time, this can lead to a narrowing of the arteries, which can reduce or block the flow of blood to vital organs such as the heart and brain. This blocking of the blood flow can lead to a heart attack or stroke.

HDL cholesterol is often called "good" cholesterol because it helps prevent the "bad" cholesterol from building up in the arteries and protects against heart disease.

Triglycerides are another type of fat in the blood that can increase the risk of heart disease.

ORVATEZ is used in patients who cannot control their cholesterol levels by diet alone. While you are taking this medicine, you should also follow a low-cholesterol diet.

ORVATEZ is used, along with a low-cholesterol diet, if you have:

• high levels of cholesterol in the blood (primary hypercholesterolaemia [heterozygous familial and non-familial]) or high levels of triglycerides in the blood (mixed hyperlipidaemia):
• • that are not well controlled with a statin alone
  • for which you have taken a statin and ezetimibe as separate tablets

• a rare inherited cholesterol condition (homozygous familial hypercholesterolaemia) that can lead to high levels of cholesterol in the blood. You may also receive other treatments.

• heart disease, ORVATEZ reduces the risk of heart attack, stroke, surgery to increase blood flow to the heart or hospitalization due to chest pain.

ORVATEZ does not help you lose weight.

2. What you need to know before you take ORVATEZ

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 ever had a liver disease,
• if you have had any unexplained abnormal blood test results indicating liver disease,
• if you are a woman who can become pregnant and are not using reliable contraceptive methods,

• if you are pregnant, trying to become pregnant or breast-feeding,

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

Warnings and precautions

Consult your doctor or pharmacist before taking ORVATEZ

• if you have had a previous stroke with bleeding in the brain, or have small amounts of fluid in the brain caused by previous strokes,
• if you have kidney problems,
• if your thyroid gland does not produce enough hormones (hypothyroidism),
• if you have had muscle pain or weakness that repeats or is unexplained or a personal or family history of muscle problems,
• if you have had previous muscle problems while taking other lipid-lowering medicines (e.g. other medicines containing "statins" or "fibrates"),
• if you regularly drink 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 called fusidic acid (used to treat bacterial infections) by mouth or by injection. The combination of fusidic acid and ORVATEZ can cause muscle problems (rhabdomyolysis),

• if you have or have had myasthenia (a disease that causes muscle weakness that can affect the muscles used for breathing) or myasthenic syndrome (a condition that causes muscle weakness of the eye muscles), as statins can sometimes worsen the condition or trigger myasthenia (see section 4).

Contact your doctor as soon as possible if you experience unexplained muscle pain, tenderness or weakness while taking ORVATEZ.This is because, on rare occasions, muscle problems can be serious, including muscle breakdown, which can cause kidney damage. Atorvastatin can cause muscle problems and muscle problems have also been reported with ezetimibe.

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 condition.

Consult your doctor or pharmacist before taking ORVATEZ:

• if you have severe respiratory failure.

If you are in any of the above situations (or are unsure), consult your doctor before taking ORVATEZ, as your doctor will need to perform a blood test before starting your treatment with ORVATEZ, and possibly during treatment, to predict the risk of muscle side effects. It is known that the risk of muscle side effects, e.g. rhabdomyolysis, increases when certain medicines are taken at the same time (see section 2 "Taking ORVATEZ with other medicines").

While you are taking this medicine, your doctor will check if you have diabetes or are at risk of developing diabetes. The risk of diabetes increases if you have high levels of sugar and fat in the blood, are overweight and have high blood pressure.

Tell your doctor about all your medical conditions, including allergies.

The combined use of ORVATEZ and fibrates (certain cholesterol-lowering medicines) should be avoided, as the combined use of ORVATEZ and fibrates has not been studied.

Children

ORVATEZ is not recommended for children and adolescents.

Taking ORVATEZ with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.

There are some medicines that can affect the way ORVATEZ works or that ORVATEZ can affect. 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 side effects, including a serious condition called "rhabdomyolysis", which is described in section 4:

• cyclosporin (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, colestyramine (medicines used to regulate lipid levels),
• certain 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),
• 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 skin structure infections and bacteremia).

** If you have to take fusidic acid by mouth to treat a bacterial infection, you will have to stop using this medicine temporarily. Your doctor will tell you when you can restart treatment with ORVATEZ. The use of ORVATEZ with fusidic acid can rarely cause muscle weakness, tenderness 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),
  • stiripentol (an anticonvulsant medicine used to treat epilepsy),
  • cimetidine (a medicine used to treat stomach acid and peptic ulcers),
  • phenazone (a pain reliever),
  • antacids (indigestion remedies that contain aluminium or magnesium),
  • warfarin, phenprocoumon, acenocoumarol or fluindione (medicines that prevent blood clots),
  • colchicine (used to treat gout),
  • St John's Wort (a medicine used to treat depression).

Taking ORVATEZ with food and drink

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

Grapefruit juice

Do not drink more than one or two small glasses of grapefruit juice per day, as large amounts of grapefruit juice can affect the way ORVATEZ works.

Alcohol

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

Pregnancy and breast-feeding

Do not take ORVATEZ if you are pregnant, trying to become pregnant or think you may be pregnant. Do not take ORVATEZ if you can become pregnant, unless you use 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 breast-feeding.

The safety of ORVATEZ during pregnancy and breast-feeding has not yet been proven.

Consult your doctor or pharmacist before taking this medicine.

Driving and using machines

ORVATEZ is not expected to affect your ability to drive or use machines. However, it should be noted that some people 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 some sugars, contact them 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".

3. How to take ORVATEZ

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

• Before starting to take ORVATEZ, you should be following a cholesterol-lowering diet.
• You should continue with this cholesterol-lowering diet while taking ORVATEZ.

How much to take

The recommended dose is one ORVATEZ tablet once a day by mouth.

Method of administration

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

If your doctor has prescribed ORVATEZ with colestyramine or any other bile acid sequestrant (medicines that lower cholesterol levels), you should 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 forget 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 further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

• severe allergic reactions that cause swelling of the face, tongue, and throat and can cause great difficulty breathing

• severe disease whose symptoms are intense exfoliation and skin inflammation, blister formation on the skin, mouth, eyes, genitals, and fever; skin rash with pink or red spots, especially on the palms of the hands or the soles of the feet, which can lead to blisters

• weakness, sensitivity, pain, or muscle rupture or change in urine color to reddish-brown 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 can 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 fact may be indicative of a liver condition.

The following frequent adverse effects have been reported (may affect up to 1 in 10 patients):

• diarrhea,
• muscle pain.

The following infrequent adverse effects have been reported (may affect up to 1 in 100 patients):

• flu,
• depression; sleep problems; sleep disorder,
• dizziness; headache; tingling sensation,
• slow heartbeat,
• hot flashes,
• 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 muscle weakness; pain in the arms and legs,
• unusual weakness; feeling of fatigue or discomfort; inflammation, especially in the ankles (edema),
• increase or decrease in blood levels of certain liver or muscle function tests (CK) in laboratory blood tests,
• weight gain.

The following adverse effects have been reported with an unknown frequency (the frequency cannot be estimated from the available data):

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

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

Additionally, the following adverse effects have been reported in people taking ORVATEZ, ezetimibe, or atorvastatin tablets:

• allergic reactions that include inflammation of the face, lips, tongue, and/or throat that can cause difficulty breathing or swallowing (which require immediate medical treatment),
• red, rash-like skin, and sometimes target-like shape,
• liver problems,
• cough,
• heartburn,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions that include the appearance of skin rash and hives,
• tendon injury,
• gallstones or gallbladder inflammation (which can cause abdominal pain, nausea, or vomiting),
• pancreatitis, often accompanied by severe abdominal pain,
• decrease in blood cell count, which can cause bruising/bleeding (thrombocytopenia),
• inflammation of the nasal passages; nosebleeds,
• neck pain; chest pain; throat pain,
• increase or decrease in blood sugar levels (if you have diabetes, you should closely monitor your blood glucose levels),
• nightmares,
• numbness or tingling in the fingers and toes,
• decreased sensitivity to pain or touch,
• alteration 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 adverse 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 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,
• 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 of Adverse Effects

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

5. Storage of ORVATEZ

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine 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.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of ORVATEZ

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

The other ingredients are: calcium carbonate; anhydrous colloidal silica; sodium croscarmellose; hydroxypropyl cellulose; lactose monohydrate; magnesium stearate; microcrystalline cellulose; polysorbate 80; povidone; sodium lauryl sulfate.

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

Appearance of the Product and Package Contents

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

ORVATEZ 10 mg/20 mg tablets: with the code "333" on one side

ORVATEZ 10 mg/40 mg tablets: with the code "337" on one side

ORVATEZ 10 mg/80 mg tablets: with the code "357" on one side

Package sizes:

Packages of 10, 30, 90, and 100 film-coated tablets in aluminum/aluminum blisters (oriented polyamide-aluminum-PVC with an aluminum cover).

Packages of 30 x 1 and 45 x 1 film-coated tablets in unit doses, aluminum/aluminum blisters (oriented polyamide-aluminum-PVC with an aluminum cover).

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

Tel.: 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 medicine is authorized in the Member States of the European Economic Area under the following names:

ORVATEZ: Germany, Greece, Italy, Portugal, and Spain

TIOBLIS: Belgium and Luxembourg

Date of the Last Revision of this Prospectus:07/2023.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es