Orvatez 10 mg/40 mg film-coated tablets

Package leaflet: Information for the user

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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It could harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See Section 4.

Contents of the leaflet

1. What ORVATEZ is and what it is used for

2. What you need to know before taking ORVATEZ

3. How to take ORVATEZ

4. Possible side effects

5. How to store ORVATEZ

6. Contents of the pack and other information

1. What ORVATEZ is and what it is used for

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

ORVATEZ is used in adults to lower total cholesterol, "bad" cholesterol (LDL cholesterol), and blood fat substances called triglycerides. In addition, ORVATEZ increases levels of "good" cholesterol (HDL cholesterol).

ORVATEZ works by reducing cholesterol in two ways: it reduces cholesterol absorbed from the digestive tract as well as 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 called "bad" cholesterol because it can build up in the walls of your arteries, forming plaques. Over time, this plaque buildup can cause narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. This interruption in blood flow may trigger 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 your blood that may increase the risk of heart disease.

ORVATEZ is used in patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must continue to follow a cholesterol-lowering diet.

ORVATEZ is used, together with a cholesterol-lowering diet, if you have:

• high blood levels of cholesterol (primary hypercholesterolemia [heterozygous familial and non-familial]) or high blood levels of fatty substances (mixed hyperlipidemia):

  • that are not well controlled with a statin alone
  • for which a statin and ezetimibe have previously been used as separate tablets

• a hereditary condition (homozygous familial hypercholesterolemia), which increases cholesterol levels in the blood. You may also receive other treatments.

• heart disease; ORVATEZ reduces the risk of heart attack, stroke, surgery to improve 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 starting 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 unexplained abnormal results in liver function blood tests,

• if you are a woman who could 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

Talk to your doctor or pharmacist before starting ORVATEZ

• if you have previously had a stroke with intracranial haemorrhage, or have small accumulations of fluid in the brain due to previous strokes,

• if you have kidney problems,

• if you have low thyroid activity (hypothyroidism),

• if you have had recurrent or unexplained muscle pain or discomfort, or a personal or family history of muscle disorders,

• if you have previously experienced muscle problems while being treated 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 certain sugars, contact your doctor before taking this medicine,

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

• if you have or have had myasthenia (a disease causing generalized muscle weakness, which in some cases affects 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 as soon as possible if you experience unexplained muscle pain, tenderness, or weakness while taking ORVATEZ. This is because, although rarely, muscle problems can be serious, including muscle breakdown leading to 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 persistent muscle weakness. Additional tests and treatments may be needed to diagnose and manage this condition.

Talk to your doctor or pharmacist before starting ORVATEZ:

• if you have severe respiratory insufficiency.

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

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

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

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

Children

ORVATEZ is not recommended in children and adolescents.

Taking ORVATEZ with other medicines

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

Some medicines may alter the effect of ORVATEZ or their effects may be altered by ORVATEZ (see section 3). This type of interaction could reduce the effectiveness of one or both medicines. It could also increase the risk or severity of adverse effects, including a serious condition involving muscle breakdown known as “rhabdomyolysis,” described in section 4:

• cyclosporine (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 and derivatives, colestipol, cholestyramine (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 in the treatment of HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (used to treat AIDS),
• some medicines used in the treatment of 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 need to take oral fusidic acid to treat a bacterial infection temporarily, you will need to stop taking ORVATEZ. Your doctor will advise you when you can restart ORVATEZ. Using ORVATEZ 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 ORVATEZ
  • oral contraceptives (medicines that prevent pregnancy),
  • stiripentol (an anticonvulsant medicine used to treat epilepsy),
  • cimetidine (a medicine used for stomach acidity and peptic ulcers),
  • phenazone (an analgesic),
  • antacids (products for treating indigestion containing aluminium or magnesium),
  • warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines that prevent blood clots),
  • colchicine (used to treat gout),
  • St. John’s wort (a herbal 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:

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 ORVATEZ.

Alcohol

Avoid excessive alcohol consumption while taking this medicine. For further 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 could 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 medicine.

Driving and using machines

ORVATEZ is not expected to affect your ability to drive or use machines. However, bear in mind that 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”.

3. How to take ORVATEZ

Follow exactly the instructions for administration of this medicine provided by your doctor. Your doctor will determine the appropriate tablet dose for you, depending on your current treatment and your individual risk situation. If in doubt, consult your doctor or pharmacist again.

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

What dose to take

The recommended dose is one ORVATEZ tablet once daily, taken orally.

Method of administration

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

If your doctor has prescribed ORVATEZ together with colestyramine or any other bile acid sequestrant (medicines 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 forget to take ORVATEZ

Do not take a double dose; the following day, take your usual amount of ORVATEZ at the usual time.

If you have any further questions about 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 everyone will experience them.

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

• severe allergic reactions causing swelling of the face, tongue, and throat, which may cause severe difficulty breathing

• a serious illness characterized by severe skin peeling and inflammation, blistering of 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 progress to blistering

• muscle weakness, tenderness, pain, or rupture, or change in urine color to red-brown, especially if accompanied by a feeling of malaise or high temperature, which may be due to abnormal muscle breakdown that could be potentially life-threatening and lead to kidney problems

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

Consult your doctor as soon as possible if you experience unexpected or unusual bleeding or bruising, as this may indicate liver disease.

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

• diarrhea,
• muscle pain.

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

• flu-like symptoms,
• depression; sleep problems; sleep disorders,
• dizziness; headache; tingling sensation,
• slow heart rate,
• hot flushes,
• choking sensations,
• abdominal pain; bloating; constipation; indigestion; flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; gastric distress,
• acne; pimples,
• joint pain; back pain; leg muscle cramps; muscle fatigue, spasms, or weakness; pain in arms and legs,
• unusual weakness; feeling tired or unwell; swelling, especially in the ankles (edema),
• increased liver or muscle function tests (CK) in laboratory blood tests,
• weight gain.

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

• myasthenia gravis (a disease causing generalized muscle weakness, which in some cases affects the muscles used for breathing),
• ocular myasthenia (a disease causing weakness of the eye muscles).

Consult your doctor if you experience worsening weakness in the arms or legs 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 swelling of the face, lips, tongue, and/or throat, which may cause difficulty breathing or swallowing (requiring immediate medical treatment),
• red skin rash, sometimes target-like in appearance,
• liver problems,
• cough,
• acid reflux,
• decreased appetite; loss of appetite,
• high blood pressure,
• skin rash and itching; allergic reactions including skin rash and hives,
• tendon injury,
• gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, or vomiting),
• inflammation of the pancreas, often accompanied by severe abdominal pain,
• decreased blood cell counts, which may lead to bruising/bleeding (thrombocytopenia),
• nasal inflammation; nosebleeds,
• neck pain; chest pain; sore throat,
• 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 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,
• high temperature,
• presence of white blood cells in urine tests,
• blurred vision; visual disturbances,
• gynecomastia (enlargement of breast tissue in men).

Possible adverse effects reported with some statins

• sexual dysfunction,
• depression,
• respiratory problems, including persistent cough and/or choking sensations or fever,
• diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight, or have high blood pressure. Your doctor will monitor you while you are taking this medicine,
• persistent muscle pain, tenderness, or weakness, especially if accompanied by malaise or high temperature, which may not resolve after stopping treatment with ORVATEZ (frequency not known).

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide 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 expiry date stated on the carton or container after "EXP" or "CAD". The expiry date refers to the last day of the month indicated.
• Store in the original packaging to protect from oxygen.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at a SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of ORVATEZ

The active substances 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 components 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.

Nature of the product and contents of the pack

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

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

Pack sizes:

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

Blister packs of 30 x 1 and 45 x 1 film-coated tablets in unit dose packs, aluminium/aluminium blisters (oriented polyamide-aluminium-PVC base with aluminium foil lid).

Only certain pack 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

The 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 European Economic Area member states under the following names:

ORVATEZ: Germany, Greece, Italy, Portugal and Spain

TIOBLIS: Belgium and Luxembourg

Date of latest review of this leaflet: 07/2023.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es