ORVATEZ 10 MG/20 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 the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. See Section 4.

Contents of the Package Leaflet

1. What is ORVATEZ and what is it used for
2. What you need to know before taking ORVATEZ
3. How to take ORVATEZ
4. Possible side effects
5. Storage of ORVATEZ
6. Contents of the pack and further information

1. What is ORVATEZ and what is it used for

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

ORVATEZ is used in adults to lower total cholesterol, "bad" cholesterol (LDL cholesterol), and a type of fat called triglycerides in the blood. Additionally, ORVATEZ increases the levels of "good" cholesterol (HDL cholesterol).

ORVATEZ works by reducing cholesterol in two ways. It reduces the cholesterol absorbed in the digestive tract, as well as the cholesterol produced by your body.

Cholesterol is one of the fatty substances found in the bloodstream. Your total cholesterol is mainly composed of LDL and HDL cholesterol.

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 narrowing of the arteries. This narrowing can slow down or interrupt blood flow to vital organs such as the heart and brain. This interruption of blood flow can trigger a heart attack or stroke.

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

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

ORVATEZ is used in patients who cannot control their cholesterol levels with diet alone. While taking this medication, you should follow a cholesterol-reducing diet.

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

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

• a hereditary disease (homozygous familial hypercholesterolemia), which increases blood cholesterol levels. 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 for chest pain.

ORVATEZ does not help you lose weight.

2. What you need to know before taking ORVATEZ

Do not take ORVATEZ

• if you are allergic to ezetimibe, atorvastatin, or any of the other ingredients of this medication (listed in section 6),
• if you have or have ever had a liver disease,
• if you have had any unexplained abnormal liver function test results,
• 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 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 resulting from previous strokes,
• if you have kidney problems,
• if your thyroid gland is underactive (hypothyroidism),
• if you have had recurring or unexplained muscle pain or a history of muscle problems,
• if you have experienced muscle problems while taking other lipid-lowering medications (e.g., other medications 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 medication,

• if you are taking or have taken in the last 7 days a medication containing fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and ORVATEZ can cause serious muscle problems (rhabdomyolysis),

• if you have or have had myasthenia (a disease that causes generalized muscle weakness that can affect the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), as statins can sometimes worsen the disease or cause 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, in rare cases, muscle problems can be serious, including muscle breakdown causing kidney damage. Atorvastatin is known to cause muscle problems, and muscle problems have also been reported with ezetimibe.

Also, inform your doctor or pharmacist if you experience constant muscle weakness. Further tests and medications may be necessary 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 situations (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 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 medications are taken simultaneously (see section 2 "Taking ORVATEZ with other medications").

While you are taking this medication, your doctor will monitor you for diabetes or the risk of developing diabetes. This risk of diabetes increases if you have high levels of sugars and fats in the blood, are overweight, and have high blood pressure.

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

The combined use of ORVATEZ and fibrates (certain medications to reduce cholesterol) 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 medications

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

There are some medications that can alter the effect of ORVATEZ or whose effects can be altered by ORVATEZ (see section 3). This type of interaction could decrease the effectiveness of one or both medications. On the other hand, it could also increase the risk or severity of side effects, including a serious disorder in which muscle destruction occurs, known as "rhabdomyolysis", which is described in section 4:

• cyclosporine (a medication often used in transplant patients),
• erythromycin, clarithromycin, telithromycin, fusidic acid**, rifampicin (medications used to treat bacterial infections),
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medications used to treat fungal infections),
• gemfibrozil, other fibrates, nicotinic acid, derivatives, colestipol, cholestyramine (medications used to regulate lipid levels),
• certain calcium channel blockers used to treat angina or high blood pressure, e.g., amlodipine, diltiazem,
• digoxin, verapamil, amiodarone (medications that regulate heart rhythm),
• medications used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (used to treat AIDS),
• certain medications used to treat hepatitis C, e.g., telaprevir, boceprevir, and the combination of elbasvir/grazoprevir,
• daptomycin (a medication 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 will temporarily need to stop using this medication. 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 section4

• Other medications that are known to interact with ORVATEZ
• • oral contraceptives (medications that prevent pregnancy),
  • stiripentol (an anticonvulsant medication used to treat epilepsy),
  • cimetidine (a medication used for stomach acidity and peptic ulcers),
  • phenazone (a pain reliever),
  • antacids (products for the treatment of indigestion that contain aluminum or magnesium),
  • warfarin, phenprocoumon, acenocoumarol, or fluindione (medications that prevent blood clot formation),
  • colchicine (used to treat gout),
  • St. John's Wort (a medication used to treat depression).

Taking ORVATEZ with food and alcohol

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 alter the effects of ORVATEZ.

Alcohol

Avoid excessive alcohol consumption while taking this medication. 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 think you may be pregnant. 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.

The safety of ORVATEZ during pregnancy and breastfeeding has not been established.

Consult your doctor or pharmacist before taking this medication.

Driving and using machines

ORVATEZ is not expected to interfere with 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, consult them before taking this medication.

ORVATEZ contains sodium

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

3. How to take ORVATEZ

Follow the instructions for administration of this medication exactly 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 should be following a cholesterol-reducing diet.
• You should continue with this cholesterol-reducing 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 day. You can take it with or without food.

If your doctor has prescribed ORVATEZ along with colestipol or any other bile acid sequestrant (medications that reduce 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 dose of ORVATEZ at the usual time.

If you have any other questions about the use of this medication, 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 immediately inform your doctor, 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 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 indicate 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 tiredness 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, including inflammation of the face, lips, tongue, and/or throat that can cause difficulty breathing or swallowing (which require immediate medical treatment),
• red, sometimes target-shaped, skin rash,
• liver problems,
• cough,
• heartburn,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions, including 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,
• altered 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 adverse effects reported with some statins

• sexual dysfunction,
• 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 your 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 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 leaflet. You can also report them directly through the Spanish Medicines Monitoring System: 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 stated on the carton or blister pack after "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 disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This 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; hydroxypropylcellulose; 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:

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

Packaging 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 Leaflet: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