Package Insert: Information for the Patient

Thervan Plus 10 mg/20 mg Film-Coated Tablets

Thervan Plus 10 mg/40 mg Film-Coated Tablets

Thervan Plus 10 mg/80 mg Film-Coated Tablets

ezetimiba/atorvastatina

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, 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 any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Thervan Plus is a medication that reduces high levels of cholesterol. This medication contains ezetimiba and atorvastatina.

Ezetimiba/atorvastatina is used in adults to reduce levels of total cholesterol, "bad" cholesterol (LDL cholesterol) and certain fatty substances called triglycerides that circulate in the blood. Additionally, ezetimiba/atorvastatina increases concentrations of "good" cholesterol (HDL cholesterol).

Ezetimiba/atorvastatina acts 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. Your total cholesterol is composed mainly 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 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 heart attack or 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 heart disease.

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

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

Ezetimiba/atorvastatina is used, along with a cholesterol-reducing diet, if you have:

?elevated levels of cholesterol in the blood (primary hypercholesterolemia [familial heterozygous and non-familial]) or elevated levels of fatty substances in the blood (mixed hyperlipidemia):

?that are not well controlled with a statin alone

?for which a statin and ezetimiba have been used in separate tablets

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

?heart disease, ezetimiba/atorvastatina reduces the risk of heart attack, stroke, heart surgery to increase blood flow to the heart, or hospitalization for chest pain.

Ezetimiba/atorvastatina does not help you lose weight.

Do not takeThervan Plus

?If you are allergic to ezetimibe, atorvastatin, or any of the other ingredients in this medicine (listed in section 6),

?If you have or have had a liver disease,

?If you have had any unexplained abnormal results in liver function blood tests,

?If you are a woman who may become pregnant and is 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 hepatitis C treatment.

Warnings and precautions

Consult your doctor or pharmacist before starting ezetimibe/atorvastatin

?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 recurring or unexplained muscle pain or discomfort, or have a personal or family history of muscle problems,

?If you have had muscle problems during previous treatment with other lipid-lowering medicines (e.g., other "statin" or "fibrate" medicines),

?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 within the last 7 days a medicine containing fusidic acid (used to treat bacterial infections) by mouth or injection. The combination of fusidic acid and ezetimibe/atorvastatin 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 ezetimibe/atorvastatin.This is because, in rare cases, muscle problems can be severe, including muscle rupture causing kidney damage. It is known that atorvastatin causes 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 problem.

Consult your doctor or pharmacist before starting ezetimibe/atorvastatin:

- If you have severe respiratory failure.

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

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

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

Combining ezetimibe/atorvastatin with fibrates (certain medicines 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 Thervan Plus

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 ezetimibe/atorvastatin or whose effects may be affected by ezetimibe/atorvastatin (see section 3). This type of interaction may reduce the effectiveness of one or both medicines. On the other hand, it may 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 structure 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 your treatment with ezetimibe/atorvastatin. The use of ezetimibe/atorvastatin 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 ezetimibe/atorvastatin

?Oral contraceptives (medicines that prevent pregnancy),

?Stiripentol (an anticonvulsant medicine used to treat epilepsy),

?Cimetidine (a medicine used to treat stomach acid and ulcers),

?Fenazone (a painkiller),

?Antacids (products used to treat indigestion containing 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 Thervan Pluswith food and alcohol

See section 3 for instructions on how to take ezetimibe/atorvastatin. 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 this medicine.

Alcohol

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

Pregnancy and breastfeeding

Do not take ezetimibe/atorvastatin if you are pregnant, trying to become pregnant, or think you may be pregnant. Do not take ezetimibe/atorvastatin if you may become pregnant, unless you are using 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 been proven.

Consult your doctor or pharmacist before taking this medicine.

Driving and operating machines

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

Thervan Plus 10 mg/20 mg and 10 mg/40 mg contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Thervan Pluscontains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; that is, it 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.

?You must be following a diet to reduce cholesterol before starting to take ezetimiba/atorvastatina.

?You will need to continue with this cholesterol-reducing diet while taking ezetimiba/atorvastatina.

What quantity to take

The recommended dose is one tablet of ezetimiba/atorvastatina once a day taken orally.

Administration form

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

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

If you take moreThervan Plusthan you should

Consult your doctor or pharmacist.

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to takeThervan Plus

Do not take an extra dose; the next day, take your normal dose of ezetimiba/atorvastatina 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 service.

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, 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 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, which 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 may be indicative of liver disease.

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

Dyspepsia,

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; numbness,

Slow heart rate,

Angina,

Shortness of breath,

Abdominal pain; abdominal distension; 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 unknown frequency (frequency cannot be estimated from available data):

Myasthenia gravis (a disease that causes generalized muscle weakness, which 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, eyelid drooping, difficulty swallowing, or difficulty breathing.

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

Severe 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, inflamed 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 hives; 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,

Altered sense of taste; dry mouth,

Memory loss,

Tinnitus and/or headache; 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,

Continuous 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 ezetimibe/atorvastatin treatment (unknown frequency).

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system: Spanish System for 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 after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

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

Composition of Thervan Plus

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

The other components are: microcrystalline cellulose, mannitol, calcium carbonate, sodium croscarmellose, hydroxypropylcellulose, polisorbate 80, yellow iron oxide (E-172), magnesium stearate, povidone and sodium lauryl sulfate.

The tablet coating contains: lactose monohydrate (Thervan Plus 10 mg/20mg and 10 mg/40 mg), hypromellose (E-464), titanium dioxide (E-171), macrogol; and talc and yellow iron oxide (E-172) (Thervan Plus 10 mg/80 mg).

Appearance of the product and content of the container

Thervan Plus 10 mg/20 mg tablets are film-coated, oval, biconvex, white in color and approximately 11.6 x 7.1 mm in size.

Thervan Plus 10 mg/40 mg tablets are film-coated, capsule-shaped, biconvex, white in color and approximately 16.1 x 6.1 mm in size.

Thervan Plus 10 mg/80 mg tablets are film-coated, oblong, biconvex, yellow in color and approximately 19.1 x 7.6 mm in size.

The tablets are available in containers with OPA/Al/PVC//Al blisters in containers of 30 tablets.

Marketing authorization holder

Laboratorios Alter, S.A.

C/ Mateo Inurria 30

28036 Madrid

Spain

Responsible for manufacturing

ELPEN Pharmaceutical Co. Inc.

Marathonos Ave. 95, Pikermi Attiki, 19009

Greece

or

ELPEN Pharmaceutical Co. Inc.

Zapani, Block 1048, Keratea, 190 01

Greece

Last review date of this leaflet: January 2024

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