Zofenil plus

Patient Information Leaflet

Zofenil Plus, 30 mg + 12.5 mg, film-coated tablets
Zofenoprilum calcicum + Hydrochlorothiazidum
Please read the entire leaflet carefully before taking the medicine, as it contains information important for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

1. What Zofenil Plus is and what it is used for
2. What you need to know 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 Zofenil Plus is and what it is used for

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

• Zofenopril calcium is a cardiovascular medicine belonging to a group of antihypertensive drugs known as angiotensin-converting enzyme (ACE) inhibitors.
• Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced.

Zofenil Plus is used in the treatment of mild to moderate arterial hypertension (high blood pressure) when treatment with zofenopril alone does not provide adequate blood pressure control.

2. Important information before using Zofenil Plus

When not to use Zofenil Plus:

• after the third month of pregnancy (Zofenil Plus should also be avoided in early pregnancy – see section "Pregnancy and breastfeeding")
• if the patient is allergic to calcium zofenopril or hydrochlorothiazide or any of the other ingredients of this medicine (listed in section 6)
• if the patient is allergic to substances derived from sulfonamides (e.g. hydrochlorothiazide, which is a sulfonamide derivative)
• if the patient has previously experienced an allergic reaction to any other ACE inhibitor medicine, such as captopril or enalapril
• if the patient has previously had severe swelling and itching of the face, nose and throat (angioedema) associated with treatment with ACE inhibitors, or in case of

hereditary/idiopathic angioedema (sudden swelling of the skin,
tissues, gastrointestinal tract and other organs)

• if the patient has taken or is currently taking sacubitril with valsartan, a medicine used to treat certain types of chronic heart failure in adults, because the risk of angioedema (rapid swelling of tissues beneath the skin, such as in the throat) increases
• in case of severe impairment of liver or kidney function
• in case of renal artery stenosis
• if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren

Warnings and precautions
Before starting treatment with Zofenil Plus, consult a doctor.
Inform your doctor:

• in case of liver or kidney disease
• if hypertension is caused by kidney dysfunction or narrowing of the arteries leading to the kidneys (renovascular hypertension)
• in case of recent kidney transplantation
• in dialysis patients
• if undergoing LDL apheresis (a procedure similar to kidney dialysis that clears harmful cholesterol deposits from the blood)
• in case of abnormal, excessively high levels of the hormone aldosterone in the blood (primary hyperaldosteronism) or reduced levels of the hormone aldosterone in the blood (hypoaldosteronism)
• in case of aortic valve stenosis or thickening of the heart walls (hypertrophic cardiomyopathy)
• in case of current or previous psoriasis (a skin disease characterized by red, scaly patches)
• during allergen immunotherapy (allergy shots) due to insect stings
• in case of systemic lupus erythematosus (an autoimmune disorder, i.e. immune system disorder)
• in case of predisposition to low blood potassium levels, especially if long QT syndrome (abnormal ECG pattern) is present or if cardiac glycosides are being taken (to support heart contractility)
• in case of diabetes
• in case of angina or cerebrovascular disorders, as low blood pressure may lead to myocardial infarction or stroke
• if the patient is taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (ARB) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney dysfunction related to diabetes
• aliskiren
• if the patient is taking any of the following medicines, the risk of angioedema (rapid swelling of the skin in areas such as the throat) may increase:
• racecadotril, a medicine used to treat diarrhea
• medicines used to prevent organ transplant rejection and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus)
• vildagliptin, a medicine used to treat diabetes
• if the patient has previously had skin cancer or if unexpected skin changes occur during treatment. Treatment with hydrochlorothiazide, especially in high doses over a long period, may increase the risk of certain types of non-melanoma skin cancers

(non-melanoma skin cancer). During treatment with Zofenil Plus, protect
the skin from sunlight and UV radiation

• if the patient experiences vision impairment or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid accumulation between choroid and sclera) or increased intraocular pressure – they may occur within hours or weeks after taking Zofenil Plus. This may lead to permanent vision loss if untreated. If the patient previously had an allergy to penicillin or sulfonamides, they may be more susceptible to developing this condition
• if the patient previously experienced breathing or lung problems (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If severe shortness of breath or breathing difficulties occur after taking Zofenil Plus, seek immediate medical help.

The treating physician may monitor kidney function, blood pressure and blood electrolyte levels (e.g.
potassium) at regular intervals.
See also information under the heading "When not to use Zofenil Plus".
Hydrochlorothiazide, a component of Zofenil Plus, may cause skin hypersensitivity to
sunlight or artificial ultraviolet radiation. Discontinue taking Zofenil Plus and consult a doctor if
rash, itchy spots or skin hypersensitivity occur during treatment (see also section 4).
Anti-doping test: Zofenil Plus may cause a positive result in anti-doping tests.

• Zofenil Plus may cause excessive lowering of blood pressure, especially after the first dose (this risk increases when taking diuretics, in case of dehydration or on a low-salt diet, or during illness or diarrhea). If this occurs, immediately contact a doctor and lie down on your back (see also section 4).

In case of surgery, before anesthesia is administered, inform the anesthesiologist that
Zofenil Plus is being taken. This will allow appropriate monitoring of the patient's blood pressure and pulse during
the procedure.
Inform your doctor if you suspect (or are planning) pregnancy. Use of Zofenil Plus is not recommended in early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child (see section "Pregnancy and breastfeeding").
Children and adolescents
Zofenil Plus must 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
Tell your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines you plan to take.
In particular, inform your doctor if you are taking:

• potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole, used in bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant 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 production of certain hormones in the body, intravenous amphotericin B, carbenoxolone, laxatives)
• lithium (used to treat mood disorders)
• anesthetic medicines
• narcotics (e.g. morphine)
• antipsychotic medicines (used to treat schizophrenia and similar disorders)
• tricyclic antidepressants, e.g. amitriptyline and clomipramine
• barbiturates (used to treat anxiety disorders, insomnia and epileptic seizures)
• other medicines used for hypertension and blood vessel dilators (including beta-blockers, alpha-blockers and diuretics such as hydrochlorothiazide, furosemide, torasemide). The treating physician may need to adjust the dose and/or take additional precautions: If the patient is taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information under the headings "When not to use Zofenil Plus" and "Warnings and precautions").
• nitroglycerin and other nitrates used to treat chest pain (angina pectoris)
• acid-neutralizing medicines, including cimetidine (used to treat heartburn and peptic ulcer disease)
• cyclosporine (used after transplants) and other immunosuppressive medicines (medicines that suppress the body's immune defenses)
• medicines used for gout (e.g. probenecid, sulfinpyrazone and allopurinol)
• insulin or oral antidiabetic medicines
• cytostatic medicines (used in cancer treatment or diseases affecting the body's immune system)
• glucocorticosteroids (potent anti-inflammatory medicines)
• procainamide (used to normalize heart rhythm)
• non-steroidal anti-inflammatory drugs (NSAIDs, e.g. aspirin or ibuprofen)
• sympathomimetic medicines (medicines acting on the nervous system, including those used to treat asthma and hay fever, and amines that increase blood pressure, e.g. adrenaline)
• calcium salts
• cardiac glycosides (used to increase heart contractility)
• cholestyramine and colestipol (cholesterol-lowering medicines)
• medicines used to relax muscles (e.g. tubocurarine)
• amantadine (an antiviral medicine)
• racecadotril (used to treat diarrhea), medicines used to prevent rejection of transplanted organs and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus) and vildagliptin (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 sufficient water.
Alcohol enhances the hypotensive (blood pressure-lowering) effect of Zofenil Plus. For detailed information on alcohol consumption during treatment, consult your doctor.
Pregnancy and breastfeeding
Pregnancy
If the patient is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult a doctor before using this medicine. The doctor will usually advise discontinuing Zofenil Plus before planned pregnancy or immediately after pregnancy is confirmed and will recommend another medicine instead of Zofenil Plus.
Use of Zofenil Plus is not recommended in early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
If the patient is breastfeeding or planning to breastfeed, she should consult a doctor before using this medicine. Inform the doctor if the patient is breastfeeding or plans to start breastfeeding. Zofenil Plus is not recommended for breastfeeding mothers. The doctor may recommend another medicine during breastfeeding, especially if breastfeeding a newborn or preterm infant.
Driving and operating machinery
The medicine may cause dizziness and fatigue. If these symptoms occur, do not drive or operate machinery.
Zofenil Plus contains lactose
This medicine contains lactose. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Zofenil Plus

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
The usual recommended dose of Zofenil Plus is one tablet per day.
Zofenil Plus may be taken with food or on an empty stomach. It is best to swallow the tablet with water.
To aid swallowing, the tablet may be divided in half and each half swallowed one after the other.
In patients over 65 years of age with impaired renal function, Zofenil Plus may not be an appropriate medicine (see also section 2, "Warnings and precautions").

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

Taking more Zofenil Plus than recommended
If you accidentally take too many tablets, contact your doctor or the nearest emergency medical facility immediately (bring any remaining tablets or this leaflet with you, if possible).
The most common symptoms and signs of overdose include abnormally low blood pressure associated with fainting (hypotension), very slow heart rate (bradycardia), changes in blood composition (electrolytes), impaired kidney function, excessive urination leading to dehydration, nausea and drowsiness, muscle cramps, and heart rhythm disturbances (particularly if digoxin or antiarrhythmic medicines are taken concomitantly).

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

Stopping Zofenil Plus
Always consult your doctor before stopping treatment with Zofenil Plus.
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.
The following adverse effects were reported during clinical studies with Zofenil Plus:
Common (may occur in fewer than 1 in 10 patients):

• Dizziness
• Headache
• Cough.

Uncommon (may occur in fewer than 1 in 100 patients):

• Sudden swelling, especially of the lips, cheeks, eyelids, tongue, palate, larynx, possibly accompanied by sudden breathing difficulties (angioedema). The occurrence of any of the above symptoms indicates a severe allergic reaction to Zofenil Plus. In such a case, the patient may require immediate medical assistance or hospitalization.
• Infection
• Bronchitis
• Sore throat
• Increased blood cholesterol and/or other fats, increased blood glucose, potassium, uric acid, creatinine and liver enzymes
• Decreased blood potassium
• Insomnia
• Drowsiness, fainting, muscle stiffness (increased muscle tone)
• Angina pectoris, myocardial infarction, atrial fibrillation, palpitations
• Sudden flushing, low blood pressure, high blood pressure
• Nausea, dyspepsia, gastritis, gingivitis, dry mouth, stomach pain
• Skin disorders characterized by scaly red patches (psoriasis), acne, dry skin, itching, urticaria
• Back pain
• Increased urine output (polyuria)
• General weakness (asthenia), influenza-like symptoms, peripheral edema (usually around the ankles)
• Impotence.

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

• Fatigue. Sudden drop in blood pressure at the beginning of treatment or when increasing the dose, accompanied by dizziness, visual disturbances, fainting; low blood pressure in the upright position.
• Chest pain, muscle pain and/or cramps.
• Impaired 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).
• Reduced kidney function, changes in daily urine volume, presence of protein in urine (proteinuria).
• Vomiting, diarrhea, constipation.
• Allergic reactions, with skin peeling, redness, loosening and blistering of the skin (toxic epidermal necrolysis), worsening of psoriasis, hair loss (alopecia).
• Excessive sweating.
• Mood changes, depression, sleep disturbances.
• Reversible skin reactions such as burning, pricking or tingling (paresthesia).
• Loss of balance, disorientation, tinnitus, taste disturbances, blurred vision.
• Breathing difficulties, narrowing of the airways in the lungs (bronchospasm), sinusitis, runny nose (rhinitis), inflammation of the tongue.
• Yellowing of the skin (jaundice), hepatitis or pancreatitis, intestinal obstruction.
• Changes in laboratory test results, e.g. red blood cell count, white blood cell count, platelet count, or decreased number of all types of blood cells (pancytopenia). If you notice a tendency to bruise easily or experience sore throat or fever without an obvious cause, you should contact your doctor.
• Increased blood bilirubin, increased blood urea.
• Anemia due to destruction of red blood cells (hemolytic anemia), which may occur in patients with G6PD deficiency (glucose-6-phosphate dehydrogenase deficiency).

The following adverse effects were not reported during clinical studies with Zofenil Plus,
but have been reported during treatment with hydrochlorothiazide, and therefore may also occur
during treatment with Zofenil Plus:

• Impaired production of new blood cells in the bone marrow (bone marrow failure).
• Fever, systemic allergic reaction (anaphylactic reaction).
• Abnormal body fluid levels (dehydration) and blood test results (electrolytes), gout, diabetes, metabolic alkalosis.
• Apathy, nervousness, anxiety.
• Seizures, decreased level of consciousness, coma, paralysis.
• Yellow vision (xanthopsia), worsening of myopia, reduced tear production, visual impairment or eye pain due to increased pressure (possible signs of fluid accumulation in the uvea—the excessive accumulation of fluid between choroid and sclera—or acute angle-closure glaucoma).
• Dizziness (sensation of spinning).
• Heart rhythm disturbances (arrhythmia), changes in electrocardiogram.
• Blood clot formation in veins (thrombosis) and embolism, circulatory collapse (shock).
• Respiratory failure, pneumonia, fibrous tissue formation in the lungs (pulmonary interstitial fibrosis), fluid accumulation in the lungs (pulmonary edema).
• Thirst, loss of appetite (anorexia), absence of intestinal peristalsis (paralytic ileus), gas accumulation in the stomach, inflammation of salivary glands (sialadenitis), increased blood amylase activity (pancreatic enzyme, hyperamylasemia), cholecystitis.
• Purple spots on the skin (purpura), increased skin sensitivity to sunlight, rash (especially on the face) and (or) red patches that may lead to scarring (cutaneous lupus erythematosus), inflammation of blood vessels leading to tissue necrosis (necrotizing vasculitis).
• Acute kidney failure (with reduced urine production and accumulation of fluid and metabolic waste products in the body), inflammation of renal connective tissue (interstitial nephritis), presence of glucose in urine.
• Frequency unknown: skin and lip malignancies (non-melanoma skin cancers).
• Very rare: acute respiratory failure (symptoms include severe shortness of breath, fever, weakness and confusion).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your 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
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Zofenil Plus

Keep the medicine 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 stated month.
Always store the tablets in the original packaging.
Medicines must not be disposed of via wastewater or household waste. Ask
your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Zofenil Plus contains
Active substances: 30 mg of calcium zofenopril and 12.5 mg of hydrochlorothiazide.
Other components:

• Tablet core: microcrystalline cellulose, lactose monohydrate, maize starch, hypromellose, colloidal anhydrous silica, magnesium stearate
• Coating: Opadry Pink 02B24436 (containing hypromellose, titanium dioxide (E 171), polyethylene glycol 400, iron oxide red (E 172)), polyethylene glycol 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 tablets are pale red, round, slightly biconvex coated tablets with a division line on one side. The division line on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure equal dosing.
Pack contents: 14, 28, 30, 50, 56, 90 or 100 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare
L-1611 Luxembourg
Luxembourg
Manufacturers
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 further information, contact the representative of the marketing authorisation holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel: (22) 566 21 00
Fax: (22) 566 21 01

This medicinal product is authorised in the European Economic Area countries 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