Alzil Plus 40 mg/10 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Alzil plus 5 mg/10 mg film-coated tablets

Alzil plus 10 mg/10 mg film-coated tablets

Alzil plus 20 mg/10 mg film-coated tablets

Alzil plus 40 mg/10 mg film-coated tablets

rosuvastatin / ezetimibe

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 you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What Alzil plus is and what it is used for

This medicine contains two different active substances in a single film-coated tablet. One of the active substances is rosuvastatin calcium, which belongs to a group of medicines called statins; the other active substance is ezetimiba.

Alzil plus is a medicine used to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and certain fatty substances called triglycerides. In addition, Alzil plus increases levels of "good" cholesterol (HDL cholesterol). This medicine works in two ways: by reducing cholesterol absorption in the gastrointestinal tract and by reducing cholesterol produced by the body itself.

For most people, high cholesterol levels do not affect how they feel, as they cause no symptoms. However, if left untreated, fatty deposits can build up in the walls of blood vessels and narrow them.

Sometimes, these narrowed blood vessels can become blocked, cutting off blood supply to the heart or brain, leading to a heart attack or stroke. By lowering cholesterol levels, your risk of having a heart attack, stroke, or other related health problems can be reduced.

This medicine 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.

Your doctor may prescribe Alzil plus if you are already taking rosuvastatin and ezetimiba at the same dose levels.

Alzil plus is used if you have:

• High blood cholesterol levels (primary hypercholesterolemia)

This medicine does not help you lose weight.

2. What you need to know before taking Alzil plus

Do not take Alzil plus if:

• you are allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6),
• you have liver disease,
• you have severe kidney problems,
• you have repeated or unexplained muscle pain or cramps (myopathy),
• you are taking a medicine called cyclosporine (used, for example, after an organ transplant),
• you are pregnant or breastfeeding. If you become pregnant while taking Alzil plus, stop taking it immediately and inform your doctor. Women should avoid becoming pregnant during treatment with this medicine by using an appropriate contraceptive method.
• If you have ever developed a severe skin rash or peeling of the skin, blisters and/or mouth sores after taking Alzil plus or other related medicines.

Additionally, do not take Rosuvastatin 40 mg (the highest dose):

• If you have moderate kidney problems (if in doubt, consult your doctor).
• If your thyroid gland is not working properly (hypothyroidism).
• If you regularly consume large amounts of alcohol.
• If you are of Asian origin (e.g., Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian).
• If you are taking other medicines called fibrates to lower cholesterol (see section “Other medicines and Alzil plus”).

If you are in any of the situations mentioned above (or are unsure), please consult your doctor again.

Warnings and precautions

Talk to your doctor or pharmacist before taking Alzil plus if:

• you have kidney problems,
• you have liver problems,
• you have repeated or unexplained muscle pain or cramps, a personal or family history of muscle disorders, or a previous history of muscle problems during treatment with other cholesterol-lowering medicines. Inform your doctor immediately if you experience unexplained muscle pain or cramps, especially if you also feel generally unwell or have a fever. Also inform your doctor or pharmacist if you experience persistent muscle weakness,
• you are of Asian origin (e.g., Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor must determine the appropriate dose of Alzil plus for you,
• you are taking medicines to treat infections, including HIV (AIDS virus) or hepatitis C, such as lopinavir/ritonavir and/or atazanavir or simeprevir. See “Other medicines and Alzil plus”,
• you have severe respiratory insufficiency,
• you are taking other medicines called fibrates to lower cholesterol; see “Taking Alzil plus with other medicines”,
• you regularly consume large amounts of alcohol,
• your thyroid gland is not working properly (hypothyroidism),
• you are over 70 years old (as your doctor must choose the appropriate dose of Alzil plus for you),
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine for bacterial infection). The combination of fusidic acid and Alzil plus may cause serious muscle problems (rhabdomyolysis),
• you have or have had myasthenia (a disease characterized by 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).

If you are in any of the above-mentioned situations (or are unsure): consult your doctor or pharmacist before starting any dose of Alzil plus.

In a small number of people, statins may affect the liver. This is detected by a simple blood test showing increased levels of liver enzymes. For this reason, your doctor will usually perform blood tests (liver function tests) during treatment with this medicine. It is important that you attend your doctor’s appointments for these tests.

While taking this medicine, your doctor will monitor you closely if you have diabetes or are at risk of developing diabetes. You are likely to be at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.

Take special care with Alzil plus:

Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with Alzil plus treatment. Stop using Alzil plus and seek immediate medical attention if you notice any of the symptoms described in section 4.

Children and adolescents

The use of Alzil plus is not recommended in children and adolescents under 18 years of age.

Other medicines and Alzil plus

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

Inform your doctor if you are taking any of the following medicines:

• Cyclosporine (used, for example, after an organ transplant to prevent organ rejection. The effect of rosuvastatin increases when taken together). Do not take Alzil plus if you are taking cyclosporine.
• Anticoagulants, such as warfarin, acenocoumarol, or phenindione (their anticoagulant effects and risk of bleeding may increase when taken with this medicine), ticagrelor, or clopidogrel.
• Other cholesterol-lowering medicines called fibrates, which also correct blood triglyceride levels (e.g., gemfibrozil and other fibrates). When used concomitantly, the effect of rosuvastatin increases.
• Colestyramine (a cholesterol-lowering medicine), as it affects how ezetimibe works.
• Medicines for indigestion containing aluminium and magnesium (used to neutralize stomach acid, as they reduce rosuvastatin plasma levels). This effect can be minimized by taking these medicines 2 hours after rosuvastatin.
• Erythromycin (an antibiotic). The effect of rosuvastatin decreases when taken together.
• Fusidic acid. If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when it is safe to restart Alzil plus. Taking this medicine with fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). More information on rhabdomyolysis can be found in section 4.
• An oral contraceptive (the pill). The levels of absorbed sex hormones are increased.
• Hormone replacement therapy (increased hormone levels in the blood).
• Regorafenib (used to treat cancer).
• any of the following medicines used to treat viral infections, including HIV or hepatitis C, alone or in combination (see Warnings and Precautions): ritonavir, lopinavir, atazanavir, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.

If you go to hospital or receive treatment for another illness, tell the medical staff that you are taking Alzil plus.

Alzil plus and alcohol

Do not take Alzil plus 40 mg/10 mg (the high dose) if you regularly consume large amounts of alcohol.

Pregnancy and breastfeeding

Do not take Alzil plus if you are pregnant, think you may be pregnant, or plan to become pregnant. If you become pregnant while taking this medicine, stop taking it immediately and inform your doctor. Women should use contraceptive methods during treatment with Alzil plus.

Do not take Alzil plus while breastfeeding, as it is unknown whether the medicine passes into breast milk.

Driving and using machines

This medicine is not expected to affect your ability to drive or use machines. However, some people may feel dizzy after taking Alzil plus. If you feel dizzy, consult your doctor before attempting to drive or use machines.

Alzil plus contains lactose

Alzil plus tablets contain a sugar called lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

Alzil plus contains sodium

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

3. How to take Alzil plus

Follow exactly the instructions for use of this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

You must continue to maintain a low-cholesterol diet and exercise regularly while taking Alzil plus.

The recommended daily dose for adults is one tablet of the prescribed strength.

Take Alzil plus once daily.

You may take it at any time of day, with or without food. Swallow each tablet whole with water.

Take your medicine at the same time each day.

Alzil plus is not suitable for initiating treatment. The initiation of treatment or dose adjustments, if necessary, should only be performed by taking the active substances separately. Once the appropriate doses have been established, switching to the corresponding strength of Alzil plus may be considered.

The maximum daily dose of rosuvastatin is 40 mg. This dose is intended only for patients with high cholesterol levels and a high risk of heart attack or stroke whose cholesterol levels do not decrease sufficiently with 20 mg.

If your doctor has prescribed Alzil plus together with other cholesterol-lowering medicines containing the active ingredient cholestyramine or another medicine containing a bile acid sequestrant, you must take Alzil plus at least 2 hours before or 4 hours after taking these medicines.

Regular monitoring of cholesterol levels

It is important that you visit your doctor regularly for cholesterol checks to ensure that your cholesterol levels have normalized and remain at appropriate levels.

If you take more Alzil plus than you should

Contact your doctor or the nearest hospital emergency department, as you may require medical assistance.

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

If you forget to take Alzil plus

Do not worry. Skip the missed dose and take the next scheduled dose at the usual time. Do not take a double dose to make up for a missed dose.

If you stop taking Alzil plus

Consult your doctor if you wish to discontinue treatment with Alzil plus. Your cholesterol levels may rise again if you stop taking Alzil plus.

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 may cause adverse effects, although not everyone will experience them.

It is important that you are aware of the possible adverse effects.

Stop taking Alzil plus and seek immediate medical help if you experience any of the following allergic reactions:

• Difficulty breathing, with or without swelling of the face, lips, tongue and/or throat.
• Swelling of the face, lips, tongue and/or throat, which may cause difficulty swallowing.
• Severe skin itching (with raised lumps).
• Reddish, non-elevated spots on the trunk, target-shaped or circular, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• Widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Also stop taking Alzil plus and consult your doctor immediately:

• If you experience unexplained muscle pain and cramps lasting longer than expected. Muscle symptoms are more common in children and adolescents than in adults. As with other statins, a very small number of people have experienced unpleasant muscle effects, which very rarely have resulted in a potentially fatal muscle injury called rhabdomyolysis.
• If you experience muscle rupture.
• If you develop lupus-like syndrome (including skin rash, joint disorders and effects on blood cells).

The following terms are used to describe how frequently adverse effects have been reported:

Very common adverse effects (may affect more than 1 in 10 people)
Common adverse effects (may affect up to 1 in 10 people)
Uncommon adverse effects (may affect up to 1 in 100 people)
Rare adverse effects (may affect up to 1 in 1,000 people)
Very rare adverse effects (may affect up to 1 in 10,000 people, including isolated cases)

Common adverse effects (may affect up to 1 in 10 people)

• Headache;
• Constipation;
• General discomfort;
• Muscle pain;
• Weakness;
• Dizziness;
• Diabetes. This is more likely if you have high blood sugar and lipid levels, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine;
• Stomach pain;
• Diarrhea;
• Flatulence (excess gas in the intestinal tract);
• Feeling tired;
• Elevated levels in certain blood tests of liver function (transaminases).
• Increased levels of protein in urine, which usually return to normal on their own without the need to discontinue treatment with Alzil plus (only for Alzil plus 40 mg/10 mg tablets).

Uncommon adverse effects (may affect up to 1 in 100 people)

• Skin rash, itching, hives;
• Increased levels of protein in urine – this usually returns to normal on its own without the need to discontinue treatment with rosuvastatin tablets (only for Alzil plus 5 mg/10 mg, 10 mg/10 mg and 20 mg/10 mg tablets).
• Elevated levels in certain blood tests of muscle function (Creatine Kinase test);
• Cough;
• Indigestion;
• Heartburn;
• Joint pain;
• Muscle spasms;
• Neck pain;
• Loss of appetite;
• Pain;
• Chest pain;
• Hot flushes;
• High blood pressure;
• Tingling sensation;
• Dry mouth;
• Inflammation of the stomach;
• Back pain;
• Muscle weakness;
• Pain in arms and legs;
• Swelling, especially of the hands and feet.

Rare adverse effects (may affect up to 1 in 1,000 people)

• Inflammation of the pancreas, causing severe stomach pain that may spread to the back; reduction in blood platelet levels.

• Lupus-like syndrome.

• Muscle rupture.

Very rare adverse effects (may affect up to 1 in 10,000 people)

Jaundice (yellowing of the skin and eyes); liver inflammation (hepatitis); traces of blood in urine; nerve damage in arms and legs (such as numbness); memory loss; enlargement of the breasts in men (gynecomastia).

Frequency not known (cannot be estimated from available data)

Difficulty breathing; edema (swelling); sleep disturbances, including insomnia and nightmares; sexual dysfunction; depression; respiratory problems including persistent cough and/or difficulty breathing or fever; tendon injuries; constant muscle weakness; gallstones or gallbladder inflammation (which may cause abdominal pain, nausea, vomiting); myasthenia gravis (a condition causing generalized muscle weakness which, in some cases, affects muscles used for breathing); ocular myasthenia (a condition causing weakness of the eye muscles).

Consult your doctor if you experience worsening weakness in your arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or difficulty breathing.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Alzil plus

Store below 25°C. Keep the container tightly closed to protect from moisture. Keep out of reach and sight of children. Do not use after the expiry date stated on the container. The expiry date refers to the last day of the month. Do not dispose of unused medication via wastewater or household waste. Ask your pharmacist how to properly dispose of medications no longer required to help protect the environment.

Keep in the original packaging to protect from light and moisture. This medicine does not require any special storage temperature.

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". The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If you have any doubts, 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 Alzil plus

The active substances are rosuvastatin (as rosuvastatin calcium) and ezetimibe.

Alzil plus 5 mg/10 mg:

Each film-coated tablet contains 5.20 mg of rosuvastatin calcium (equivalent to 5 mg of rosuvastatin) and 10 mg of ezetimibe.

Alzil plus 10 mg/10 mg:

Each film-coated tablet contains 10.40 mg of rosuvastatin calcium (equivalent to 10 mg of rosuvastatin) and 10 mg of ezetimibe.

Alzil plus 20 mg/10 mg:

Each film-coated tablet contains 20.80 mg of rosuvastatin calcium (equivalent to 20 mg of rosuvastatin) and 10 mg of ezetimibe.

Alzil plus 40 mg/10 mg:

Each film-coated tablet contains 41.60 mg of rosuvastatin calcium (equivalent to 40 mg of rosuvastatin) and 10 mg of ezetimibe.

• The other components are:

Tablet – Core (same for all strengths): Microcrystalline cellulose (E460); Anhydrous colloidal silica (E-551); Magnesium stearate (E-572); Povidone (E-1201); Sodium croscarmellose (E-468); Sodium lauryl sulfate (E-487); Lactose monohydrate; Hypromellose (E-464).

Coating:

Opadry Yellow (5mg/10mg): Hypromellose (E-464); Titanium dioxide (E-171); Macrogol (E-1521); Yellow iron oxide (E-172); Talc (E-553b); Red iron oxide (E-172).

Opadry Beige (10mg/10mg): Hypromellose (E-464); Titanium dioxide (E-171); Macrogol (E-1521); Yellow iron oxide (E-172); Talc (E-553b).

Vivacoat Yellow (20mg/10mg): Hypromellose (E-464); Titanium dioxide (E-171); Macrogol (E-1521); Yellow iron oxide (E-172); Talc (E-553b).

Opadry White (40mg/10mg): Lactose monohydrate; Hypromellose (E-464); Titanium dioxide (E-171); Macrogol (E-1521).

Appearance of the product and contents of the pack

Alzil plus 5 mg/10 mg film-coated tablets are light yellow, round, biconvex tablets with an approximate diameter of 10 mm, marked “EL 5” on one side.

Alzil plus 10 mg/10 mg film-coated tablets are beige, round, biconvex tablets with an approximate diameter of 10 mm, marked “EL 4” on one side.

Alzil plus 20 mg/10 mg film-coated tablets are yellow, round, biconvex tablets with an approximate diameter of 10 mm, marked “EL 3” on one side.

Alzil plus 40 mg/10 mg film-coated tablets are white, round, biconvex tablets with an approximate diameter of 10 mm, marked “EL 2” on one side.

Alzil plus is available in packs with blisters containing 30 and 100 tablets.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Ferrer Internacional, S.A.

Gran Vía Carlos III, 94

08028 – Barcelona (Spain)

Manufacturer

Elpen Pharmaceutical Co. Inc.

Marathonos 95

190 09 Pikermi – Attica (Greece)

or

ELPEN Pharmaceutical Co Inc

Zapani, Block 1048

Keratea, 19001, (Greece)

or

Rontis Hellas Medical and Pharmaceutical Products S.A.

P.O. BOX 3012 Larissa Industrial Area

Larissa, 41500, Greece

This medicinal product is authorized in the European Economic Area member states under the following names:

Spain:

Alzil plus 5 mg/10 mg film-coated tablets

Alzil plus 10 mg/10 mg film-coated tablets

Alzil plus 20 mg/10 mg film-coated tablets

Alzil plus 40 mg/10 mg film-coated tablets

Portugal:

Rosuvastatin + Ezetimibe Ferrer 5 mg + 10 mg film-coated tablets

Rosuvastatin + Ezetimibe Ferrer 10 mg + 10 mg film-coated tablets

Rosuvastatin + Ezetimibe Ferrer 20 mg + 10 mg film-coated tablets

Rosuvastatin + Ezetimibe Ferrer 40 mg + 10 mg film-coated tablets

Date of the most recent review of this leaflet: April 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/