Romazic plus

Patient Information Leaflet

Romazic Plus, 5 mg + 10 mg, film-coated tablets
Romazic Plus, 10 mg + 10 mg, film-coated tablets
Romazic Plus, 20 mg + 10 mg, film-coated tablets
Romazic Plus, 40 mg + 10 mg, film-coated tablets
Rosuvastatinum + Ezetimibum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you specifically. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

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

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

Romazic Plus contains two different active substances in one tablet. One of the active substances is rosuvastatin, belonging to a group of medicines called statins, and the other active substance is ezetimibe.
Romazic Plus is a medicine used to reduce blood levels of total cholesterol, so-called "bad" cholesterol (LDL cholesterol), and fatty substances called "triglycerides", while also increasing levels of so-called "good" cholesterol (HDL cholesterol). The medicine reduces cholesterol levels by acting in two ways: by decreasing the amount of cholesterol absorbed in the gastrointestinal tract and by reducing the amount of cholesterol produced in the body.
In most people, high cholesterol does not affect well-being, as it causes no symptoms. However, if left untreated, fatty deposits may accumulate in the walls of blood vessels, causing them to narrow.
As a result of narrowing, blood vessels may occasionally become completely blocked, cutting off blood supply to the heart or brain, leading to a heart attack or stroke. By lowering cholesterol levels, the risk of heart attack, stroke, or other similar health problems can be reduced.
Romazic Plus is used in patients whose cholesterol levels cannot be controlled by a cholesterol-lowering diet alone. While taking this medicine, you should continue to follow a cholesterol-lowering diet.
Your doctor may prescribe Romazic Plus if you are already taking rosuvastatin and ezetimibe at the same doses as those contained in the combination medicine.
Romazic Plus is used in patients:

• with increased blood cholesterol levels (primary hypercholesterolemia)
• with heart disease – Romazic Plus reduces the risk of heart attack, stroke, the need for a surgical procedure to improve blood flow to the heart, or hospitalization due to chest pain.

Romazic Plus does not help reduce body weight.

2. What you need to know before taking Romazic Plus

When not to take Romazic Plus

• if you are allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6);
• if you have liver disease;
• if you have severe kidney function impairment;
• if you experience recurrent, unexplained muscle pain (myopathy);
• if you are taking the combination sofosbuvir/velpatasvir/voxilaprevir (used to treat viral hepatitis C);
• if you are taking a medicine containing cyclosporine (used, for example, after organ transplantation);
• if you are pregnant or breastfeeding. If you become pregnant while taking Romazic Plus, you must stop taking the medicine immediately and inform your doctor. While taking Romazic Plus, you must avoid becoming pregnant by using effective contraception.
• if you have previously experienced severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking Romazic Plus or other similar medicines.

Additionally, do not take Romazic Plus 40 mg + 10 mg (the highest dose):

• if you have moderately severe kidney disease (if in doubt, consult your doctor);
• if you have been diagnosed with thyroid dysfunction (hypothyroidism);
• if you have recurrent or unexplained muscle aches or pain, or if you or a family member has had muscle disorders, or if you previously experienced muscle-related problems while taking cholesterol-lowering medicines;
• if you regularly consume large amounts of alcohol;
• if you are of Asian descent (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian);
• if you are taking other cholesterol-lowering medicines called fibrates (see section "Romazic Plus and other medicines").

If any of the above situations apply to you (or if you have any doubts), you should contact your doctor.

Warnings and precautions

Before starting Romazic Plus, discuss with your doctor if:

• you have kidney function problems;

• you have liver function problems;

• you have experienced recurrent or unexplained muscle aches or pain, or if you or your relatives have had muscle disorders, or if you previously had muscle-related problems while taking other cholesterol-lowering medicines. If you experience unexplained muscle aches or pain, especially if accompanied by malaise or fever, contact your doctor immediately. You should also inform your doctor or pharmacist if you experience persistent muscle weakness.

• you are of Asian descent (Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian). Your doctor will determine the appropriate dose of Romazic Plus for you.

• you are taking antiviral medicines, including those used to treat HIV or hepatitis C virus infection, e.g. lopinavir, ritonavir, atazanavir, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, and/or pibrentasvir (see section "Romazic Plus and other medicines");

• you have severe respiratory insufficiency;

• you are taking other cholesterol-lowering medicines called fibrates. See section "Romazic Plus and other medicines".

• you are scheduled for surgery. It may be necessary to temporarily stop taking Romazic Plus.

• you regularly consume large amounts of alcohol;

• you have been diagnosed with thyroid dysfunction (hypothyroidism);

• you are over 70 years of age (as your doctor should determine the appropriate dose of Romazic Plus for you);

• you are taking or have taken within the last 7 days, orally or by injection, a medicine called fusidic acid (used to treat bacterial infections). Concomitant use of fusidic acid and Romazic Plus may lead to serious muscle problems (rhabdomyolysis).

• if you are taking a medicine containing regorafenib (used to treat cancer);

• you have or have had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), as statins may sometimes worsen symptoms or trigger the onset of myasthenia (see section 4). If any of the above situations apply to you (or if you have any doubts), contact your doctor or pharmacist before starting Romazic Plus.

In a small number of people, statins may affect liver function. This is detected by a simple blood test measuring increased liver enzyme activity. Your doctor will therefore recommend regular blood tests while you are taking Romazic Plus. It is important that you attend your doctor's appointments for these tests.
Severe skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of Romazic Plus. If you experience any of the symptoms described in section 4, stop taking Romazic Plus and contact your doctor immediately.
While taking this medicine, your doctor will closely monitor patients with diabetes or risk factors for developing diabetes. There is an increased risk of developing diabetes if you have high blood sugar and fat levels, overweight, and high blood pressure.

Children and adolescents
Romazic Plus is not recommended for use in children and adolescents under 18 years of age.

Romazic Plus and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Inform your doctor if you are taking any of the following medicines:

• cyclosporine (a medicine used, for example, after organ transplantation to prevent organ rejection. Cyclosporine increases the effect of rosuvastatin taken simultaneously). Do not take Romazic Plus while taking cyclosporine.
• anticoagulants, e.g. warfarin, acenocoumarol, fluindione, ticagrelor, or clopidogrel (concomitant use with Romazic Plus may enhance anticoagulant effects, increasing the risk of bleeding);
• other cholesterol-lowering medicines, so-called fibrates, which also regulate blood triglyceride levels (e.g. gemfibrozil and other medicines in this group). Concomitant use increases the effect of rosuvastatin.
• cholestyramine (a medicine used to reduce cholesterol levels), as it affects the way ezetimibe works;
• medicines used to treat indigestion containing aluminium and magnesium (used to neutralize stomach acid). These medicines may reduce rosuvastatin plasma levels. This effect can be minimized by taking these medicines 2 hours after taking rosuvastatin.
• erythromycin (an antibiotic). Concomitant use reduces the effect of rosuvastatin.
• fusidic acid. If you need to take fusidic acid orally to treat a bacterial infection, temporary discontinuation of Romazic Plus will be necessary. Your doctor will inform you when it is safe to resume taking it. Concomitant use of Romazic Plus and fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). More information on rhabdomyolysis can be found in section 4.
• oral contraceptives (birth control pills). Concomitant use increases blood levels of sex hormones released from the pill.
• hormone replacement therapy medicines (increased hormone levels in blood);
• regorafenib (used to treat cancer);
• any of the following antiviral medicines used to treat viral infections, including HIV or hepatitis C virus infection, used alone or in combination (see "Warnings and precautions"): ritonavir, lopinavir, atazanavir, simeprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir, sofosbuvir, voxilaprevir.

If you are admitted to hospital or being treated for another illness, you should inform medical staff that you are taking Romazic Plus.

Romazic Plus and alcohol
Do not take Romazic Plus at the dose of 40 mg + 10 mg (the highest dose) if you regularly consume large amounts of alcohol.

Pregnancy and breastfeeding
Do not take Romazic Plus if you are pregnant, trying to become pregnant, or think you may be pregnant. If you become pregnant while taking Romazic Plus, stop taking it immediately and inform your doctor. While taking Romazic Plus, you should use effective contraception.
Do not take Romazic Plus while breastfeeding, as it is not known whether the medicine passes into human milk.

Driving and using machines
Romazic Plus should not affect your ability to drive or operate machinery. However, bear in mind that Romazic Plus may cause dizziness in some patients. If this occurs, do not drive or operate machinery.

Romazic Plus contains lactose
If you have been previously diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

Romazic Plus contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Romazic Plus

This medicine should always be taken as instructed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
While taking Romazic Plus, continue a cholesterol-lowering diet and maintain physical activity.
The recommended daily dose for adults is one tablet of a given strength.
Romazic Plus should be taken once daily.
Romazic Plus can be taken at any time of day, with or without food. Tablets should be swallowed whole
with water.
The medicine should be taken at the same time each day.
Romazic Plus is not suitable for initiating treatment. If starting therapy or if a dose adjustment is required,
each active substance should be taken separately in individual medicinal products. Only after the appropriate
doses have been established should the patient switch to Romazic Plus of a specified strength.
If your doctor has prescribed Romazic Plus together with another cholesterol-lowering medicine
containing the active substance cholestyramine or any other medicine containing bile acid sequestrants
(bile acid-binding medicines), Romazic Plus should be taken at least 2 hours before or 4 hours after taking
such medicines.
Regular monitoring of cholesterol levels
It is important to visit your doctor regularly to monitor your cholesterol levels, to ensure that target levels
have been achieved and are being maintained.
Taking more Romazic Plus than recommended
In case of overdose, contact your doctor or the emergency department of the nearest hospital, as medical
assistance may be necessary.
Missing a dose of Romazic Plus
If a dose is missed, take the next tablet at the usual time. Do not take a double dose to make up for the
missed dose.
Stopping Romazic Plus
Inform your doctor if you wish to discontinue taking Romazic Plus. After stopping Romazic Plus, cholesterol
levels may rise again.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
It is important for the patient to be aware of possible adverse effects.
The use of Romazic Plus must be stopped immediately and medical advice must be sought without delay
if the patient experiences:

• any unexplained muscle pain, tenderness or weakness persisting longer than expected. This is because muscle problems, including muscle breakdown leading to kidney damage, can be serious and potentially life-threatening

(rhabdomyolysis). This adverse effect is rare (occurs in no more than 1 in 1,000 people).

• severe allergic reaction (angioedema) – symptoms include swelling of the face, lips, tongue and (or) throat, difficulty in swallowing and breathing, severe skin itching (with hives). This adverse effect is rare (occurs in no more than 1 in 1,000 people).
• red, flat, disc-shaped or circular rash on the trunk, often with blisters in the center, skin peeling, mouth ulcers, ulcers in the throat, nose, genital organs and around the eyes. Such serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• extensive rash, high fever and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• muscle rupture
• symptoms of a lupus-like syndrome (including rash, joint problems and effects on blood cells).

Other known adverse effects
Adverse effects occurring frequently (occur in less than 1 in 10 patients):

• diabetes. The risk of developing diabetes is higher if the patient has high levels of blood sugar and fats, overweight and high blood pressure. The treating physician will monitor patients at risk during treatment with this medicine.
• headache
• dizziness
• constipation
• nausea
• abdominal pain
• diarrhea
• bloating (excess gas in the gastrointestinal tract)
• muscle pain
• weakness
• feeling of fatigue
• increased results of certain blood tests assessing liver function (aminotransferase activity)
• increased amount of protein in urine. This symptom usually resolves spontaneously and treatment with Romazic does not need to be discontinued (applies only to the rosuvastatin 40 mg dose).

Adverse effects occurring not very frequently (occur in less than 1 in 100 patients):

• decreased appetite
• tingling sensation
• hot flushes
• high blood pressure
• cough
• indigestion
• heartburn
• dry mouth
• gastritis
• rash, itching, urticaria
• joint pain
• muscle cramps
• neck pain
• back pain
• muscle weakness
• pain in arms and legs
• chest pain
• pain
• swelling, especially of hands and feet
• elevated results of certain laboratory blood tests assessing muscle function (creatine kinase test)
• increased amount of protein in urine may occur – usually returns to normal spontaneously, without the need to discontinue treatment (only rosuvastatin doses 10 mg and 20 mg).

Adverse effects occurring rarely (occur in less than 1 in 1,000 patients):

• bleeding or bruising more easily than usual due to low platelet count
• pancreatitis causing severe abdominal pain which may radiate to the back
• symptoms of a lupus-like syndrome (including rash, joint problems and effects on blood cells)
• muscle rupture.

Adverse effects occurring very rarely (occur in less than 1 in 10,000 patients):

• nerve damage in arms and legs (such as numbness)
• memory loss
• jaundice (yellowing of the skin and eyes)
• hepatitis
• blood in urine
• breast enlargement in men (gynaecomastia).

Adverse effects occurring with unknown frequency (cannot be estimated from available data):

• depression
• sleep disorders, including insomnia and nightmares
• myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing)
• ocular myasthenia (a disease causing weakness of eye muscles)
• shortness of breath
• gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea, vomiting)
• tendon injury
• persistent muscle weakness
• sexual dysfunction
• breathing problems, including persistent cough and (or) shortness of breath or fever
• swelling (edema)
• muscle tenderness
• raised red rash, sometimes with disc-shaped lesions (erythema multiforme).

Patients should consult a doctor if they experience weakness in arms or legs worsening after periods of activity, double vision or drooping eyelids, difficulty in swallowing or shortness of breath.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Romazic Plus

Keep this medicine out of sight and reach of children.
Store in the original packaging to protect from light and moisture. There are no special
requirements regarding storage temperature.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP.
The expiry date refers to the last day of the stated month.
The marking on the packaging following EXP indicates the expiry date, and following Lot/LOT indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Romazic Plus contains
The active substances in this medicine are rosuvastatin (in the form of rosuvastatin calcium) and ezetimibe.
Romazic Plus, 5 mg + 10 mg:
Each film-coated tablet contains 5 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe.
Romazic Plus, 10 mg + 10 mg:
Each film-coated tablet contains 10 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe.
Romazic Plus, 20 mg + 10 mg:
Each film-coated tablet contains 20 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe.
Romazic Plus, 40 mg + 10 mg:
Each film-coated tablet contains 40 mg of rosuvastatin (as rosuvastatin calcium) and 10 mg of ezetimibe.

Other ingredients are:
Tablet core (the same for all strengths): microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate, povidone K30, sodium croscarmellose, sodium lauryl sulfate, monohydrate lactose, hypromellose.

Coating:
Romazic Plus, 5 mg + 10 mg: hypromellose, titanium dioxide (E 171), macrogol, yellow iron oxide (E 172), red iron oxide (E 172), talc.
Romazic Plus, 10 mg + 10 mg: hypromellose, titanium dioxide (E 171), macrogol, yellow iron oxide (E 172), talc.
Romazic Plus, 20 mg + 10 mg: hypromellose, titanium dioxide (E 171), macrogol, yellow iron oxide (E 172), talc.
Romazic Plus, 40 mg + 10 mg: monohydrate lactose, hypromellose, titanium dioxide (E 171), macrogol.

What Romazic Plus looks like and contents of the pack
Romazic Plus, 5 mg + 10 mg: Light yellow, round, biconvex film-coated tablets with a diameter of approximately 10 mm, marked with "EL 5" on one side.
Romazic Plus, 10 mg + 10 mg: Beige, round, biconvex film-coated tablets with a diameter of approximately 10 mm, marked with "EL 4" on one side.
Romazic Plus, 20 mg + 10 mg: Yellow, round, biconvex film-coated tablets with a diameter of approximately 10 mm, marked with "EL 3" on one side.
Romazic Plus, 40 mg + 10 mg: White, round, biconvex film-coated tablets with a diameter of approximately 10 mm, marked with "EL 2" on one side.

Pack contents: 28, 30, 56, 60, 84 or 100 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
ELPEN Pharmaceutical Co. Inc.,
Marathonos Ave. 95
19009 Pikermi Attiki, Greece
RONTIS HELLAS MEDICAL AND PHARMACEUTICAL PRODUCTS S.A.
P.O BOX 3012 Larissa Industrial Area
41500 Larissa, Greece