ALZIL PLUS 40 MG/10 MG FILM-COATED TABLETS

2. What you need to know before you take 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 pains or cramps (myopathy),
• you are taking a medicine called ciclosporin (used, for example, after an organ transplant to prevent rejection of the transplanted organ),
• you are pregnant or breast-feeding. 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 using an appropriate contraceptive method.
• If you have ever developed a severe skin rash or peeling of the skin, blisters, and/or sores in the mouth after taking Alzil plus or other related medicines.

In addition, 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 does not work properly (hypothyroidism)
• If you regularly drink large amounts of alcohol.
• If you are of Asian origin (for example, Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian).
• If you are taking other cholesterol-lowering medicines called fibrates (see "Other medicines and Alzil plus").

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Alzil plus if:

• you have kidney problems,
• you have liver problems,
• you have repeated or unexplained muscle pains or cramps, a personal or family history of muscle problems, or a previous history of muscle problems during treatment with other cholesterol-lowering medicines. Inform your doctor immediately if you have unexplained muscle pain, cramps, or weakness, especially if you also feel unwell or have a fever. Also, inform your doctor or pharmacist if you experience persistent muscle weakness,
• you are of Asian origin (for example, Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor should 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 failure,
• you are taking other cholesterol-lowering medicines called fibrates, see "Taking Alzil plus with other medicines",
• you regularly drink large amounts of alcohol,
• your thyroid gland does not work properly (hypothyroidism),
• you are over 70 years old, (since your doctor should choose the appropriate dose of Alzil plus for you).
• you are taking or have taken in the last 7 days a medicine called fusidic acid (an antibiotic). The combination of fusidic acid and Alzil plus can cause serious muscle problems (rhabdomyolysis).
• you have or have had myasthenia (a disease characterized by generalized muscle weakness that can affect the muscles used for breathing) or ocular myasthenia (a disease that causes weakness of the eye muscles), since statins can sometimes worsen the disease or cause myasthenia (see section 4).

If you are in any of these situations (or are unsure): consult your doctor or pharmacist before starting to take any dose of Alzil plus.

In a small number of people, statins can affect the liver. This is detected by a simple blood test that detects increased levels of liver enzymes in the blood. For this reason, your doctor will normally perform blood tests (liver function tests) during treatment with this medicine. It is important that you go to the doctor to have these tests done.

While taking this medicine, your doctor will closely monitor you 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 fat in your blood, are overweight, and have high blood pressure.

Be careful with Alzil plus:

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

Children and adolescents

Alzil plus is not recommended for use 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 take any other medicines.

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

• Ciclosporin (used, for example, after an organ transplant to prevent rejection of the transplanted organ. The effect of rosuvastatin increases with concomitant use). Do not take Alzil plus if you are taking ciclosporin.
• Anticoagulants, such as warfarin, acenocoumarol, or fluindione (their anticoagulant effects and the risk of bleeding may increase while taking this medicine), ticagrelor, or clopidogrel.
• Other cholesterol-lowering medicines called fibrates, which also correct triglyceride levels in the blood (e.g., gemfibrozil and other fibrates). During concomitant use, the effect of rosuvastatin increases.
• Colestyramine (a medicine to lower cholesterol), because it affects how ezetimibe works.
• Treatments for indigestion that contain aluminum and magnesium (used to neutralize stomach acid, as they reduce the level of rosuvastatin in the blood). This effect can be mitigated by taking these types of medicines 2 hours after rosuvastatin.
• Erythromycin (an antibiotic). The effect of rosuvastatin decreases with concomitant use.
• Fusidic acid. If you need to take oral fusidic acid to treat a bacterial infection, you should temporarily stop taking this medicine. Your doctor will tell you when you can safely take Alzil plus again. Taking this medicine with fusidic acid can rarely cause muscle weakness, pain, or sensitivity (rhabdomyolysis). You can find more information about rhabdomyolysis in section 4.
• An oral contraceptive (the pill). The levels of sex hormones absorbed from the pill are increased.
• Hormone replacement therapy (increased levels of hormones in the blood).
• Regorafenib (indicated for the treatment of 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 the hospital or receive treatment for another illness, tell the medical staff that you are taking Alzil plus.

Alzil plus with alcohol

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

Pregnancy and breast-feeding

Do not take Alzil plus if you are pregnant, think you may be pregnant, or are planning 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 if you are breast-feeding, as it is not known 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 told you that you have an intolerance to some sugars, consult them before taking this medicine.

Alzil plus contains sodium

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

3. How to take Alzil plus

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

You should continue to follow a cholesterol-lowering diet while taking Alzil plus.

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

Take Alzil plus once a day.

You can 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 start of treatment or dose adjustments, if necessary, should only be done by taking the active substances separately, and once the appropriate doses have been adjusted, it is possible to switch to the appropriate dose of Alzil plus.

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

If your doctor has prescribed Alzil plus with other cholesterol-lowering medicines that contain the active substance colestyramine or another medicine that contains a bile acid sequestrant, you should take Alzil plus at least 2 hours before or 4 hours after taking these medicines.

Regular checks of cholesterol levels

It is important that you go to your doctor regularly to have your cholesterol levels checked, in order to verify that your cholesterol levels have normalized and are maintained at appropriate levels.

If you take more Alzil plus than you should

Contact your doctor or the nearest hospital emergency department immediately, as you may need medical attention.

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

If you forget to take Alzil plus

Do not worry, skip the missed dose and take the next scheduled dose at the planned time. Do not take a double dose to make up for missed doses.

If you stop taking Alzil plus

Consult your doctor if you want to stop taking Alzil plus. Your cholesterol levels may increase again if you stop taking Alzil plus.

If you have any further questions on 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.

It is essential that you know what these adverse effects can be.

Stop taking Alzil plus and seek immediate medical attentionif 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 can cause difficulty swallowing.
• Severe skin itching (with raised bumps).
• Reddish patches on the torso, target-shaped or circular, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• Widespread rash, high body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

Also, stop taking Alzil plus and consult your doctor immediately:

• If you experience unjustified muscle pain and crampsthat last 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 suffered unpleasant muscle effects that have very rarely resulted in a potentially fatal muscle injury called rhabdomyolysis.
• If you experience muscle rupture.
• If you present with a lupus-like syndrome(including skin rash, joint disorders, and effects on blood cells).

The following terms are used to describe how often 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;
• High levels in some blood test results of liver function (transaminases).
• Increased amount of protein in urine, which usually reverses on its own without the need to interrupt 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;
• An increase in the amount of protein in urine – this usually reverses on its own without the need to interrupt treatment with rosuvastatin tablets (only for Alzil plus 5 mg/10 mg, 10 mg/10 mg, and 20 mg/10 mg).
• High levels in some blood test results of muscle function (Creatine Kinase test);
• Cough;
• Indigestion;
• Heartburn;
• Joint pain;
• Muscle spasms;
• Neck pain;
• Decreased appetite;
• Pain;
• Chest pain;
• Hot flashes;
• High blood pressure;
• Tingling sensation;
• Dry mouth;
• Stomach inflammation;
• Back pain;
• Muscle weakness;
• Pain in the arms and legs;
• Swelling, especially of the hands and feet.

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

• Pancreatitis, which causes severe stomach pain that can extend to the back; reduction of 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); blood traces in urine; nerve damage in the legs and arms (such as numbness); memory loss; increased breast size 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 can cause abdominal pain, nausea, vomiting); 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.

Reporting adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, 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: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Alzil plus

Keep in the original packaging to protect it 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 expiration date that appears on the carton or packaging after "EXP". The expiration date is the last day of the month indicated.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE point. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Alzil plus

The active ingredients 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 ingredients are:

Tablet – Core (same for all doses):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 package contents

Alzil plus 5 mg/10 mg film-coated tablets are light yellow, round, biconvex tablets with a diameter of approximately 10 mm and marked "EL 5" on one side.

Alzil plus 10 mg/10 mg film-coated tablets are beige, round, biconvex tablets with a diameter of approximately 10 mm and marked "EL 4" on one side.

Alzil plus 20 mg/10 mg film-coated tablets are yellow, round, biconvex tablets with a diameter of approximately 10 mm and marked "EL 3" on one side.

Alzil plus 40 mg/10 mg film-coated tablets are white, round, biconvex tablets with a diameter of approximately 10 mm and marked "EL 2" on one side.

Alzil plus is available in blister packs of 30 and 100 tablets.

Only certain package 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 medicine is authorized in the Member States of the European Economic Area 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 last revision of this leaflet:April 2023

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/