Zofenil Plus

Leaflet attached to the packaging: patient information

Zofenil Plus, 30 mg + 12.5 mg, film-coated tablets

Zofenopril calcium + Hydrochlorothiazide

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including those not listed in the leaflet, you should tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

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

Zofenil Plus contains as active substances 30 mg of zofenopril calcium and 12.5 mg of hydrochlorothiazide.

• Zofenopril calcium is a medicine that acts on the cardiovascular system, belonging to a group of medicines that lower blood pressure called angiotensin-converting enzyme inhibitors (ACE inhibitors).
• Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced. Zofenil Plus is used to treat high blood pressure (mild to moderate hypertension) when zofenopril monotherapy does not provide adequate blood pressure control.

2. Important information before taking Zofenil Plus

When not to take Zofenil Plus:

• after the third month of pregnancy (you should also avoid taking Zofenil Plus in early pregnancy - see "Pregnancy and breastfeeding")

in the past. If you have had a severe swelling and itching of the face, lips, tongue, and throat (angioedema) while being treated with ACE inhibitors, or if you have had hereditary or idiopathic angioedema (sudden swelling of the skin, tissues, gastrointestinal tract, and other organs)

Warnings and precautions

You should consult your doctor before starting treatment with Zofenil Plus.

You should inform your doctor:

liveror kidneyproblemskidney transplanton dialysisLDL apheresis(a procedure similar to kidney dialysis that cleans the blood of harmful cholesterol deposits)abnormal, high levelsof the hormone aldosteronein the blood (primary aldosteronism) or low levelsof the hormone aldosteronein the blood (hypoaldosteronism)narrowing of the heart valve(aortic stenosis) or thickening of the heart muscle(hypertrophic cardiomyopathy)psoriasis(a skin disease characterized by red, scaly patches)
• if you are receiving desensitization treatment(allergy injections) for insect stings
systemic lupus erythematosus(an immune system disorder)tendency to low potassium levelsin the blood, especially if you have a prolonged QT interval (abnormal ECG reading) or are taking digitalis glycosides (to support heart contraction)diabetes
• angiotensin II receptor antagonist (ARB) (also known as sartans - e.g. valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes
• aliskiren
• racecadotril, a medicine used to treat diarrhea
• medicines used to prevent rejection of transplanted organs and to treat cancer (e.g. temsirolimus, sirolimus, everolimus)
• wildagliptin, a medicine used to treat diabetes

The doctor may monitor kidney function, blood pressure, and electrolyte levels (e.g. potassium) in the blood at regular intervals.

See also the information under the heading "When not to take Zofenil Plus".

Hydrochlorothiazide, a component of Zofenil Plus, may cause increased sensitivity of the skin to sunlight or artificial ultraviolet radiation. You should stop taking Zofenil Plus and consult your doctor if you experience a rash, itching spots, or skin sensitivity during treatment (see also section 4).

Doping test:Zofenil Plus may cause a positive doping test result.

• Zofenil Plus may cause excessive lowering of blood pressure, especially after the first dose of the medicine (this risk is increased when taking diuretics, in case of dehydration, or when following a low-salt diet, or in case of illness or diarrhea). If this happens, you should immediatelycontact your doctor and then lie down on your back (see also section 4).

In case of surgery, before anesthesia is administered, you should inform the anesthesiologistthat you are taking Zofenil Plus. This will allow for proper control of your blood pressure and heart rate during the procedure.

You should inform your doctor if you suspect or plan to become pregnant. It is not recommended to take Zofenil Plus in early pregnancy and it should not be taken after the third month of pregnancy, as it may seriously harm the baby (see "Pregnancy and breastfeeding").

Children and adolescents

Zofenil Plus should not be used in children and adolescents under 18 years of age, as its use is likely to be unsafe.

Zofenil Plus and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

In particular, you should tell your doctor about taking:

• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that increase potassium levels in the blood (e.g. trimethoprim and co-trimoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ rejection, and heparin, a medicine used to thin the blood to prevent clots)
• medicines that affect blood test results (adrenocorticotropic hormone-ACTH used to stimulate the production of certain hormones in the body, amphotericin B injections, carbenoxolone, laxatives)
• lithium (used to treat mood disorders)
• anesthetics
• narcotics (e.g. morphine)
• antipsychotic medicines (used to treat schizophrenia and other similar diseases)
• tricyclic antidepressants (e.g. amitriptyline and clomipramine)
• barbiturates (used to treat anxiety, insomnia, and seizures)
• other medicines used to treat high blood pressure and medicines that dilate blood vessels (including beta-adrenergic blockers, alpha-adrenergic blockers, and diuretics, such as hydrochlorothiazide, furosemide, and torasemide) Your doctor may need to change the dose and/or take other precautions: If you are taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also the information under the heading "When not to take Zofenil Plus" and "Warnings and precautions").
• nitroglycerin and other nitrates used to treat chest pain (angina pectoris)
• antacids, including cimetidine (used to treat heartburn and stomach ulcers)
• cyclosporine (used after transplants) and other immunosuppressive medicines (medicines that weaken the body's defense mechanisms)
• medicines used to treat gout (e.g. probenecid, sulfinpyrazone, and allopurinol)
• insulin or oral antidiabetic medicines
• cytotoxic medicines (used to treat cancer or diseases that affect the immune system)
• glucocorticoids (strong anti-inflammatory medicines)
• procainamide (used to regulate heart rhythm)
• non-steroidal anti-inflammatory medicines (NSAIDs, e.g. aspirin or ibuprofen)
• sympathomimetic medicines (medicines that act on the nervous system, including those used to treat asthma and hay fever, and amines that increase blood pressure, e.g. adrenaline)
• calcium salts
• digitalis glycosides (used to increase the strength of heart contractions)
• cholestyramine and colestipol (used to lower cholesterol levels in the blood)
• muscle relaxants (e.g. tubocurarine)
• amantadine (an antiviral medicine)
• racecadotril (used to treat diarrhea), medicines used to prevent rejection of transplanted organs and to treat cancer (e.g. temsirolimus, sirolimus, everolimus), and wildagliptin (a medicine used to treat diabetes). The risk of angioedema may increase.

Zofenil Plus with food, drink, and alcohol

Zofenil Plus can be taken with or without food, always with a sufficient amount of water.

Alcohol increases the blood pressure-lowering effect of Zofenil Plus. For more information about consuming alcohol while taking Zofenil Plus, you should consult your doctor.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, you should consult your doctor before taking this medicine. Your doctor will usually advise you to stop taking Zofenil Plus before planned pregnancy or as soon as possible after confirmation of pregnancy and will advise you to take a different medicine instead of Zofenil Plus.

Zofenil Plus is not recommended during early pregnancy and should not be taken after the third month of pregnancy, as it may seriously harm the baby.

Breastfeeding

If you are breastfeeding or plan to breastfeed, you should consult your doctor before taking this medicine. You should inform your doctor if you are breastfeeding or plan to breastfeed. Zofenil Plus is not recommended for breastfeeding mothers. Your doctor may advise you to take a different medicine while breastfeeding, especially if you are breastfeeding a newborn or premature baby.

Driving and using machines

The medicine may cause dizziness and fatigue. If you experience these symptoms, you should not drive or operate machinery.

Zofenil Plus contains lactose

This medicine contains lactose. If you have been diagnosed with an intolerance to some sugars, you should consult your doctor before taking the medicine.

3. How to take Zofenil Plus

This medicine should always be taken as directed by your doctor. If you are unsure, you should consult your doctor or pharmacist.

The recommended dose of Zofenil Plus is one tablet per day.

Zofenil Plus can be taken with or without food, always with a sufficient amount of water.

To swallow the tablet, you can divide it into two halves and swallow one half after the other.

In patients over 65 years of age with kidney problems, Zofenil Plus may not be a suitable medicine (see also section 2 "Warnings and precautions").

Use in children and adolescents

Zofenil Plus should not be used in children and adolescents under 18 years of age.

Taking a higher dose of Zofenil Plus than recommended

If you accidentally take too many tablets, you should immediately contact your doctor or the nearest emergency department (taking any remaining tablets or this leaflet with you, if possible).

The most common symptoms and signs of overdose are: excessively low blood pressure with fainting (hypotension), very slow heart rate (bradycardia), changes in blood composition (electrolytes), kidney problems, excessive urination leading to dehydration, nausea, and drowsiness, muscle cramps, heart rhythm disorders (especially when taking digitalis glycosides or anti-arrhythmic medicines).

Missing a dose of Zofenil Plus

If you miss a dose, you should take the next dose as soon as you remember. However, if it is almost time for your next dose, you should skip the missed dose and take the next planned dose at the usual time. Do not take a double dose to make up for the missed tablet.

Stopping treatment with Zofenil Plus

You should always consult your doctor before stopping treatment with Zofenil Plus.

If you have any further questions about taking this medicine, you should ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Zofenil Plus can cause side effects, although not everybody gets them.

During clinical trials with Zofenil Plus, the following side effects were reported:

Common(may affect up to 1 in 10 people):

• Dizziness
• Headache
• Cough

Uncommon(may affect up to 1 in 100 people):

• Sudden swelling, especially of the face, lips, tongue, and throat, with possible difficulty breathing (angioedema). The occurrence of any of these symptoms indicates a severe allergic reaction to Zofenil Plus. In such cases, you may need immediate medical attention or hospitalization.
• Infection
• Bronchitis
• Sore throat
• Increased levels of cholesterol and/or other fats in the blood, increased levels of glucose, potassium, uric acid, creatinine, and liver enzymes
• Decreased levels of potassium in the blood
• Insomnia
• Drowsiness, fainting, muscle stiffness (increased muscle tone)
• Angina pectoris, heart attack, atrial fibrillation, palpitations
• Flushing, low blood pressure, high blood pressure
• Nausea, indigestion, gastritis, gum inflammation, dry mouth, stomach pain
• Skin diseases characterized by red, scaly patches (psoriasis), acne, dry skin, itching, hives
• Back pain
• Increased urine production (polyuria)
• General weakness (asthenia), flu-like symptoms, peripheral edema (usually around the ankles)
• Impotence

The following side effects were not reported during clinical trials with Zofenil Plus, but have been reported during treatment with zofenopril calcium and/or other ACE inhibitors, so they may also occur with Zofenil Plus:

• Fatigue. Sudden drop in blood pressure at the start of treatment or when increasing the dose, with accompanying dizziness, visual disturbances, and fainting; low blood pressure when standing up.
• Chest pain, muscle pain and/or cramps.
• Disorders of consciousness, sudden dizziness, sudden visual disturbances or feeling of weakness and/or loss of sensation on one side of the body (transient ischemic attack or stroke).
• Decreased kidney function, changes in daily urine output, presence of proteins in the urine (proteinuria).
• Vomiting, diarrhea, constipation.
• Allergic reactions, with skin peeling, redness, loosening, and blistering (toxic epidermal necrolysis), exacerbation of psoriasis, hair loss (alopecia).
• Excessive sweating.
• Mood changes, depression, sleep disorders.
• Reversible skin reactions, such as burning, stinging, or tingling (paresthesia).
• Balance disorders, disorientation, tinnitus, taste disorders, blurred vision.
• Breathing difficulties, bronchospasm, sinusitis, rhinitis (hay fever).
• Jaundice, hepatitis, or pancreatitis, intestinal obstruction.
• Changes in laboratory test results, such as red blood cell count, white blood cell count, platelet count, or decreased counts of all blood cell types (pancytopenia). If you notice a tendency to bruise or experience throat pain and fever without apparent cause, you should contact your doctor.
• Increased levels of bilirubin in the blood, increased levels of urea.
• Anemia due to the breakdown of red blood cells (hemolytic anemia), which may occur in people with a deficiency of G6PD (glucose-6-phosphate dehydrogenase).

The following side effects were not reported during clinical trials with Zofenil Plus, but have been reported during treatment with hydrochlorothiazide, so they may also occur with Zofenil Plus:

• Disorders of blood cell production in the bone marrow (bone marrow failure).
• Fever, allergic reaction affecting the whole body (anaphylactic reaction).
• Abnormal fluid levels in the body (dehydration) and blood test results (electrolytes), gout, diabetes, metabolic alkalosis.
• Apathy, nervousness, anxiety.
• Seizures, decreased level of consciousness, coma, paresis.
• Yellow vision, worsening of myopia, decreased tear production, eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive accumulation of fluid between the choroid and sclera - or acute angle-closure glaucoma).
• Dizziness (feeling of spinning).
• Heart rhythm disorders (arrhythmia), changes in electrocardiogram.
• Blood clots in the veins (thrombosis) and embolism, circulatory collapse (shock).
• Respiratory failure, pneumonia, lung tissue scarring (interstitial lung disease), fluid accumulation in the lungs (pulmonary edema).
• Thirst, loss of appetite (anorexia), intestinal paralysis (adynamic ileus), gas accumulation in the stomach, salivary gland inflammation (sialadenitis), increased amylase activity in the blood (pancreatic enzyme, hyperamylasemia), gallbladder inflammation.
• Purpura (purple spots on the skin), increased skin sensitivity to sunlight, rash (especially on the face) and/or red spots that may cause scarring (cutaneous lupus erythematosus), vasculitis leading to tissue necrosis (necrotizing vasculitis).
• Acute kidney failure (with decreased urine production and fluid accumulation in the body), interstitial kidney tissue inflammation (interstitial nephritis), presence of sugar in the urine.
• Unknown frequency: malignant skin tumors and lip tumors (non-melanoma skin tumors).
• Very rare: acute respiratory failure (symptoms include severe shortness of breath, fever, weakness, and confusion).

Reporting side effects

If you experience any side effects, including those not listed in the leaflet, you should tell your doctor or pharmacist.

Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zofenil Plus

The medicine should be stored out of sight and reach of children.

Do not store above 30°C.

Do not use this medicine after the expiry date stated on the packaging and blister after: EXP.

The expiry date refers to the last day of the month stated.

You should always store the tablets in their original packaging.

Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Zofenil Plus contains

The active substancesare: 30 mg of zofenopril calcium and 12.5 mg of hydrochlorothiazide.

The other ingredientsare:

• Tablet core: microcrystalline cellulose, lactose monohydrate, maize starch, hypromellose, colloidal anhydrous silica, magnesium stearate
• Coating: Opadry Pink 02B24436 (containing hypromellose, titanium dioxide (E 171), macrogol 400, iron oxide red (E 172)), macrogol 6000. See section 2 "Zofenil Plus contains lactose".

What Zofenil Plus looks like and contents of the pack

Zofenil Plus 30 mg + 12.5 mg film-coated tablets are pale red, round, slightly biconvex tablets with a score line on one side. The score line on the tablet is only to facilitate breaking and not to divide it into equal doses.

The pack contains 14, 28, 30, 50, 56, 90, or 100 film-coated tablets.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare

L-1611 Luxembourg

Luxembourg

Manufacturer

• A. Menarini Manufacturing Logistics and Services S.r.l. Campo di Pile 67100 L’Aquila Italy

Menarini - Von Heyden GmbH

Leipziger Strasse 7-13

• 01097 – Dresden Germany

For more information, you should contact the representative of the marketing authorization holder:

Berlin-Chemie/Menarini Polska Sp. z o.o.

Tel: (22) 566 21 00

Fax: (22) 566 21 01

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria: Zofenil Plus

Bulgaria: Zofen Plus

Estonia: Zofistar HCT

France: Zofenilduo

Germany: Zofenil Plus

Greece: Zofepril-Plus

Ireland: Zofenil Plus

Italy: Bifrizide

Latvia: Zofistar Plus

Lithuania: Zofistar Plus

Luxembourg: Zofenil Plus

Poland: Zofenil Plus

Portugal: Zofenil Plus

Romania: Zomen Plus 30 mg/12,5 mg comprimate filmate

Slovakia: Zofaril HCT

Slovenia: Tenzopril HCT

Spain: Zofenil Diu

Netherlands: Zofil HCTZ

Date of last revision of the leaflet:12/2021