EZETIMIBA 10 mg/20 mg Film-Coated Tablets

2. What you need to know before you take Ezetimibe/Atorvastatin Olpha

• 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 disease that affects the liver,
• if you have had any unexplained abnormal blood test results for liver function,
• 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 are 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 ezetimibe/atorvastatin

• if you have had a previous stroke with bleeding in the brain, or have small accumulations of fluid in the brain derived from previous strokes,
• if you have kidney problems,
• if your thyroid gland has low activity (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 medicine,
• if you are taking or have taken in the last 7 days a medicine that contains fusidic acid, (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and ezetimibe/atorvastatin can cause serious muscle problems (rhabdomyolysis),
• if you have or have had myasthenia (a disease that causes generalized muscle weakness that, in some cases, affects 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 to appear (see section 4).

Contact your doctor as soon as possible if you experience unexplained muscle pain, sensitivity, or weakness while taking ezetimibe/atorvastatin.This is because, in rare cases, muscle problems can be serious, including muscle breakdown that causes 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. Tests and additional medications may be necessary to diagnose and treat this problem.

Consult your doctor or pharmacist before starting to take ezetimibe/atorvastatin:

• 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 ezetimibe/atorvastatin, as your doctor will need to perform a blood test before starting your treatment with ezetimibe/atorvastatin, and possibly during treatment, to predict the risk you present of experiencing muscle side effects. It is known that the risk of experiencing muscle side effects, e.g., rhabdomyolysis, increases when certain medications are taken simultaneously (see section 2 “Other medicines and Ezetimibe/Atorvastatin Olpha”).

While you are taking this medicine, your doctor will check if you have diabetes or are at 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.

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

The combined use of ezetimibe/atorvastatin and fibrates (certain medications to lower cholesterol) should be avoided, as the combined use of ezetimibe/atorvastatin and fibrates has not been studied.

Children

Ezetimibe/atorvastatin is not recommended for children and adolescents.

Other medicines and Ezetimibe/Atorvastatin Olpha

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

There are some medicines that can modify the effect of ezetimibe/atorvastatin or whose effects may be affected by ezetimibe/atorvastatin (see section 3). This type of interaction could decrease 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 disorder in which muscle breakdown occurs, known as “rhabdomyolysis”, which is described in section 4:

• cyclosporin (a medicine used often 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 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, ledipasvir/sofosbuvir,

• Letermovir, a medicine that helps prevent you from getting sick with cytomegalovirus

• daptomycin (a medicine used to treat complicated skin and skin structure infections and bacteremia).

** If you have to take oral fusidic acid to treat a bacterial infection, you will temporarily have to stop using this medicine. Your doctor will tell you when you can restart treatment with ezetimibe/atorvastatin. The use of ezetimibe/atorvastatin with fusidic acid can rarely cause muscle weakness, sensitivity, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

• Other medicines that are known to interact with ezetimibe/atorvastatin
• • 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 (a pain reliever),
  • antacids (products for the treatment of indigestion that contain aluminum or magnesium),
  • warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines that prevent blood clot formation),
  • colchicine (used to treat gout),
  • St. John's Wort (a medicine used to treat depression).

Taking Ezetimibe/Atorvastatin Olpha with food and drink

See section 3 for instructions on how to take ezetimibe/atorvastatin. Please note the following:

Grapefruit juice

Do not take more than one or two small glasses of grapefruit juice per day, as large amounts of grapefruit juice can alter the effects of ezetimibe/atorvastatin.

Alcohol

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. Do not take ezetimibe/atorvastatin if you can become pregnant, unless you use reliable contraceptive methods. If you become pregnant while taking ezetimibe/atorvastatin, stop taking it immediately and inform your doctor.

Do not take ezetimibe/atorvastatin if you are breastfeeding.

The safety of ezetimibe/atorvastatin during pregnancy and breastfeeding has not yet been proven.

Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Ezetimibe/atorvastatin 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 ezetimibe/atorvastatin.

Ezetimibe/Atorvastatin Olpha contains lactose

The tablets of Ezetimibe/Atorvastatin 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.

Ezetimibe/Atorvastatin Olpha contains sodium

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

3. How to take Ezetimibe/Atorvastatin Olpha

Follow exactly the administration instructions of this medicine 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 ezetimibe/atorvastatin, you should be following a cholesterol-lowering diet.
• You should continue with this cholesterol-lowering diet while taking ezetimibe/atorvastatin.

How much to take

The recommended dose is one tablet of ezetimibe/atorvastatin once a day by mouth.

Method of administration

Take Ezetimibe/Atorvastatin Olpha at any time of the day. You can take it with or without food.

If your doctor has prescribed ezetimibe/atorvastatin along with colestyramine or any other bile acid sequestrant (medicines that lower cholesterol levels), you should take ezetimibe/atorvastatin at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe/Atorvastatin Olpha than you should

Consult your doctor or pharmacist.

If you forget to take Ezetimibe/Atorvastatin Olpha

Do not take a double dose to make up for forgotten doses. The next day, take your normal amount of ezetimibe/atorvastatin at the usual time.

If you have any other 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 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, feeling of discomfort or high temperature that can 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 liver disease.

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; swelling especially in the ankles (edema),
• increase in some liver or muscle function tests (CK) in laboratory blood tests,
• weight gain.

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

• 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 and sometimes target-shaped skin rash,
• liver problems,
• cough,
• acid reflux,
• 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).
• 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 the arms or legs that worsens after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or difficulty breathing.

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 sugars and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine,
• pain, sensitivity, or muscle weakness that is constant and especially, if it occurs at the same time, feeling of discomfort or high temperature that may not disappear after stopping treatment with ezetimibe/atorvastatin (frequency not known).

Adverse Effect Reporting

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 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 Ezetimibe/Atorvastatin Olpha

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the carton or packaging after "EXP". The expiration date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in 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 Ezetimibe/Atorvastatin Olpha

The active ingredients are ezetimibe and atorvastatin. Each film-coated tablet contains 10 mg of ezetimibe and 10 mg, 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; povidone, magnesium stearate; microcrystalline cellulose; polysorbate 80; sodium lauryl sulfate (E487).

The tablet coating contains: hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol, talc.

Appearance of the Product and Package Contents

Film-coated tablets, biconvex, capsule-shaped, white to off-white.

Ezetimibe/Atorvastatin Olpha 10 mg/10 mg tablets EFG: with "1T" engraved on one side.

Ezetimibe/Atorvastatin Olpha 10 mg/20 mg tablets EFG: with "2T" engraved on one side.

Ezetimibe/Atorvastatin Olpha 10 mg/40 mg tablets EFG: with "4T" engraved on one side.

Ezetimibe/Atorvastatin Olpha 10 mg/80 mg tablets EFG: with "8T" engraved on one side.

Package sizes:

Packages of 10, 30, 90, and 100 film-coated tablets in aluminum/aluminum blisters.

Only some package sizes may be marketed.

Marketing Authorization Holder

Olpha AS,

Rupnicu iela 5,

Olaine, Olaines novads, LV-2114,

Latvia

Manufacturer

Delorbis Pharmaceuticals LTD,

17 Athinon street,

Ergates Industrial Area,

2643 Ergates Lefkosia,

Cyprus

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

Date of the last revision of this leaflet: November 2024

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