Thervan Plus 10 mg/80 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Thervan Plus 10 mg/20 mg film-coated tablets EFG

Thervan Plus 10 mg/40 mg film-coated tablets EFG

Thervan Plus 10 mg/80 mg film-coated tablets EFG

ezetimibe/atorvastatin

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

• Keep this leaflet as 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, because it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Thervan Plus is and what it is used for

Thervan Plus is a medicine that lowers high cholesterol levels. This medicine contains ezetimibe and atorvastatin.

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

Ezetimibe/atorvastatin works by reducing cholesterol in two ways: by decreasing cholesterol absorbed in the gastrointestinal tract and by reducing cholesterol produced by the body itself.

Cholesterol is one of the fatty substances found in the bloodstream. Your total cholesterol consists 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 plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. Such disruption in blood flow may trigger a heart attack or stroke.

HDL cholesterol is often called "good" cholesterol because it helps prevent "bad" cholesterol from accumulating in the arteries, thus protecting against heart disease.

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

Ezetimibe/atorvastatin 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.

Ezetimibe/atorvastatin is used, together with a cholesterol-lowering diet, if you have:

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

? that are not well controlled with a statin alone

? who have previously taken a statin and ezetimibe as separate tablets

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

? heart disease; ezetimibe/atorvastatin reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization due to chest pain.

Ezetimibe/atorvastatin does not help you lose weight.

2. What you need to know before taking Thervan Plus

Do not take Thervan Plus

? 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 ezetimibe/atorvastatin

? 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 your thyroid gland is underactive (hypothyroidism),

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

? if you 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 ezetimibe/atorvastatin 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 ezetimibe/atorvastatin. 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 have persistent muscle weakness. Additional tests and treatments may be needed to diagnose and manage this condition.

Talk to your doctor or pharmacist before starting 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 ezetimibe/atorvastatin, as your doctor may need to perform a blood test before starting and possibly during treatment with ezetimibe/atorvastatin to assess your risk of developing muscle-related side effects. The risk of muscle-related adverse effects, e.g., rhabdomyolysis, is known to increase when certain medicines are taken at the same time (see section 2 “Taking Thervan Plus 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 levels of blood sugar and fats, are overweight, and have high blood pressure.

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

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

Children

Ezetimibe/atorvastatin is not recommended in children and adolescents.

Other medicines and Thervan Plus

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

Some medicines may alter the effect of ezetimibe/atorvastatin or their effects may be affected by ezetimibe/atorvastatin (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 side 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, 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),

? certain 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, you will need to temporarily stop taking this medicine. Your doctor will advise you when you can restart ezetimibe/atorvastatin treatment. The use of ezetimibe/atorvastatin with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information about rhabdomyolysis, see section 4

? Other medicines 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 painkiller),

? 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 medicine used to treat depression).

Taking Thervan Plus with food and alcohol

See section 3 for instructions on how to take ezetimibe/atorvastatin. 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 may alter the effects of this medicine.

Alcohol

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

Consult your doctor or pharmacist before taking this medicine.

Driving and using machines

Ezetimibe/atorvastatin is not expected to affect your ability to drive or use machines. However, bear in mind that 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 your doctor before taking this medicine.

Thervan Plus contains sodium

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

3. How to take Thervan Plus

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

? Before starting ezetimibe/atorvastatin, you should already be on a cholesterol-lowering diet.

? You should continue this cholesterol-lowering diet while taking ezetimibe/atorvastatin.

How much to take

The recommended dose is one tablet of ezetimibe/atorvastatin once daily by oral route.

Method of administration

Take ezetimibe/atorvastatin at any time of day. You may take it with or without food.

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

If you take more Thervan Plus than you should

Consult your doctor or pharmacist.

In case of overdose or accidental ingestion, contact your doctor, pharmacist, or call the Toxicology Information Service immediately at 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Thervan Plus

Do not take a double dose; the next day, take your usual 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 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 lead to 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 blisters

? muscle weakness, tenderness, pain, or rupture, or change in urine color to red-brown, and particularly if occurring together with malaise or high temperature, which may be due to abnormal muscle breakdown that can 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 frequently (may affect up to 1 in 10 patients):

? diarrhea,

? muscle pain.

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

? flu,

? depression; sleep disturbances; sleep disorders,

? dizziness; headache; tingling sensation,

? slow heart rate,

? hot flushes,

? shortness of breath,

? abdominal pain; bloating; constipation; indigestion; flatulence; frequent bowel movements; stomach inflammation; nausea; stomach discomfort; stomach upset,

? acne; hives,

? joint pain; back pain; leg 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 (CK) function tests in laboratory blood analyses,

? 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 that, in some cases, affects 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 ezetimibe/atorvastatin tablets, ezetimibe, or atorvastatin:

? 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-shaped,

? liver problems,

? cough,

? acid reflux,

? decreased appetite; loss of appetite,

? high blood pressure,

? skin rash and itching; allergic reactions including skin rash and hives,

? traumatic 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 count, 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 shortness of breath or fever,

? diabetes. This is more likely if you have high levels of sugar and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine,

? persistent muscle pain, tenderness, or weakness, and especially if occurring together with malaise or high temperature that does not resolve after stopping ezetimibe/atorvastatin treatment (frequency not known).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the national reporting system: 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 Thervan Plus

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Unused medicines and their containers should be returned to the SIGRE point at your pharmacy. If in doubt, ask your pharmacist how to dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of Thervan Plus

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

The tablet coating contains: monohydrate lactose (Thervan Plus 10 mg/20 mg 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 contents of the pack

Thervan Plus 10 mg/20 mg tablets are film-coated, oval-shaped, biconvex, white tablets with approximate dimensions of 11.6 x 7.1 mm.

Thervan Plus 10 mg/40 mg tablets are film-coated, capsule-shaped, biconvex, white tablets with approximate dimensions of 16.1 x 6.1 mm.

Thervan Plus 10 mg/80 mg tablets are film-coated, oblong, biconvex, yellow tablets with approximate dimensions of 19.1 x 7.6 mm.

The tablets are available in blister packs made of OPA/Al/PVC//Al, in pack sizes of 30 tablets.

Marketing Authorization Holder

Laboratorios Alter, S.A.

C/ Mateo Inurria 30

28036 Madrid

Spain

Manufacturer

ELPEN Pharmaceutical Co. Inc.

Marathonos Ave. 95, Pikermi Attiki, 19009

Greece

or

ELPEN Pharmaceutical Co. Inc.

Zapani, Block 1048, Keratea, 190 01

Greece

Date of the most recent revision of this leaflet: January 2024

Detailed 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/).