Zofenopril and hydrochlorothiazide EG

Italy
Brand name Zofenopril and hydrochlorothiazide EG
Form tablets, film-coated
Active substance / Dosage
HYDROCHLOROTHIAZIDE
ZOFENOPRIL CALCIUM
Prescription type Prescription only
ATC code
C09BA15
Registration number 043863
Manufacturer EG S.P.A.
Zofenopril and hydrochlorothiazide EG tablets, film-coated

Table of Contents

Package leaflet: Information for the user

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG 30 mg/12.5 mg film-coated tablets

Equivalent medicine
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, because it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet:

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

1. What ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is and what it is used for

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG contains 30 mg of zofenopril calcium and 12.5 mg of
hydrochlorothiazide as active substances.
Zofenopril calcium is a cardiovascular medicine belonging to a group of drugs that lower
blood pressure, known as angiotensin-converting enzyme (ACE) inhibitors.
Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced.
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is used to treat mild to moderate
high blood pressure (hypertension) when it cannot be controlled by taking zofenopril alone.

2. What you should know before taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG

Do not take ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG:

if you are more than three months pregnant (it is also advisable to avoid ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG in the early stages of pregnancy – see section "Pregnancy");
if you are allergic to zofenopril or hydrochlorothiazide or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to other sulfonamide-derived substances (such as hydrochlorothiazide, which is a sulfonamide derivative);
if you have previously experienced allergic reactions to another ACE inhibitor such as captopril or enalapril;
if you have a history of severe swelling and itching around the face, nose, and throat (angioedema) associated with prior therapy with ACE inhibitors, or if you suffer from hereditary/idiopathic angioedema (rapid swelling of the skin, tissues, gastrointestinal tract, and other organs);
if you have severe liver or kidney problems;
if you have narrowing of the renal arteries;
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, e.g., in the throat).
If you are taking any of the following medicines, the risk of angioedema may be increased:

  • Racecadotril, a medicine used to treat diarrhoea.
  • Medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus).
  • Vildagliptin, a medicine used to treat diabetes.

Warnings and precautions

Talk to your doctor before taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG if:

  • you have liver or kidney problems;

  • you have high blood pressure due to a kidney problem or narrowing of the artery supplying the kidneys (renovascular hypertension);

  • you have recently undergone a kidney transplant;

  • you are on dialysis;

  • you are undergoing LDL apheresis (a procedure similar to kidney dialysis that removes harmful cholesterol from your blood);

  • you have abnormally high levels of the hormone aldosterone in your blood (primary hyperaldosteronism);

  • you have narrowing of a heart valve (aortic stenosis) or thickening of the heart walls (hypertrophic cardiomyopathy);

  • you have or have had psoriasis (a skin condition characterized by scaly, pink patches);

  • you are undergoing desensitization therapy ("allergy shots") for insect stings;

  • you suffer from systemic lupus erythematosus (an autoimmune disorder, a condition affecting your body's immune defense system);

  • you tend to have low potassium levels in your blood, especially if you have long QT syndrome (a type of ECG abnormality) or are taking digitalis (to support heart pump function);

  • you have diabetes;

  • you suffer from angina or conditions affecting the brain, as low blood pressure may lead to heart attack or stroke;

  • you are taking any of the following blood pressure medicines:

    • an "angiotensin II receptor antagonist" (AIIRA), also known as sartans (e.g., valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes;
    • aliskiren.

  • you are taking any of the following medicines, which may increase the risk of angioedema (rapid subcutaneous swelling, e.g., in the throat):

    • sirolimus, everolimus, and other drugs belonging to the class of mTOR inhibitors (used to prevent rejection of transplanted organs);
    • if you have had skin cancer in the past or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin and lip cancer. Protect your skin from exposure to sunlight and UV radiation while taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG;
    • if you experience vision disturbances or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur from a few hours to weeks after taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG. This condition may lead to permanent vision loss if not treated. If you have previously had allergic reactions to penicillin or sulfonamides, you may be at higher risk of developing this condition;
    • if you have previously experienced respiratory or lung problems (including lung inflammation or fluid accumulation) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG, consult a doctor immediately.

Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals.
See also the section "Do not take ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG".

The hydrochlorothiazide contained in ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG may cause increased skin sensitivity to sunlight or artificial UV light. Discontinue taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG and inform your doctor if you develop a rash, itchy skin, or skin sensitivity during treatment (see also section 4).

Antidoping tests: ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG may lead to positive results in antidoping tests.

If your blood pressure becomes too low during treatment with ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG, especially after the first dose (this is more likely if you are also taking other diuretics, are dehydrated, on a low-salt diet, or have an illness or diarrhoea), inform your doctor immediately and lie down on your back (see also section 4).

If you are scheduled for surgery, inform the anaesthetist that you are taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG before receiving anaesthesia. This will help the anaesthetist manage your blood pressure and heart rate during the procedure.

Inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant).
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the baby if taken during this period (see section "Pregnancy").

Children and adolescents
The use of ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is not recommended in children and adolescents under 18 years of age, as safety has not been established.

Other medicines and ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

  • potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase blood potassium levels (such as trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent clotting);
  • other medicines affecting blood chemical levels (adrenocorticotropic hormone - ACTH - used to stimulate the body's production of certain hormones; intravenous amphotericin B; carbenoxolone; stimulant laxatives);
  • lithium (used to treat mood disorders);
  • anaesthetics;
  • narcotic medicines (such as morphine);
  • antipsychotic medicines (used to treat schizophrenia and similar conditions);
  • tricyclic antidepressants, e.g., amitriptyline and clomipramine;
  • other blood pressure medicines and vasodilators (including beta-blockers, alpha-blockers, and diuretics such as hydrochlorothiazide, furosemide, torasemide);
  • nitroglycerin and other nitrates used for chest pain (angina);
  • antacids including cimetidine (used to treat heartburn and stomach ulcers);
  • immunosuppressive medicines (medicines that suppress your body's immune defenses);
  • medicines used for gout (e.g., probenecid, sulfinpyrazone, allopurinol);
  • insulin and other oral antidiabetics;
  • cytostatic agents (used in cancer treatment or immune system disorders);
  • corticosteroids (potent anti-inflammatory medicines);
  • procainamide (used to control irregular heartbeat);
  • non-steroidal anti-inflammatory drugs (NSAIDs, such as aspirin or ibuprofen);
  • sympathomimetic medicines (medicines acting on the nervous system, including some used for asthma, hay fever, and pressor amines such as adrenaline);
  • calcium salts;
  • digitalis (used to support heart pump function);
  • cholestyramine and colestipol resins (used to lower cholesterol);
  • medicines used to relax muscles (e.g., tubocurarine);
  • amantadine (an antiviral medicine);
  • medicines typically used to prevent rejection of transplanted organs (sirolimus, everolimus, and other mTOR inhibitors). See section "Warnings and precautions".

Your doctor may need to adjust your dose and/or take additional precautions if:

  • you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "Do not take ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG" and "Warnings and precautions").

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG with food, drinks, and alcohol
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG can be taken with or without food, but always with water. To facilitate swallowing, the tablet may be split into two parts, to be taken one after the other.
Alcohol enhances the blood pressure-lowering effect (hypotensive effect) of ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG; consult your doctor for further advice on alcohol consumption while taking this medicine.

Pregnancy and breastfeeding
Pregnancy
Inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine.
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is not recommended during pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the baby if taken beyond the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed.
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is not recommended for women who are breastfeeding. Your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a newborn or was born prematurely.

Driving and using machines
This medicine may cause dizziness or fatigue. If you experience these symptoms, do not drive or operate machinery.

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG contains lactose monohydrate
If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG contains sunset yellow FCF aluminium lake (E110)
This substance may cause allergic reactions.

ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.
The recommended dose of ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG is one tablet per day.
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG may be taken with or without food. It is preferable to take the tablet with water.

Use in children and adolescents
The use of this medicine is not recommended in children and adolescents under 18 years of age.
If you are over 65 years old and have impaired kidney function, ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG may not be the appropriate medicine for you (see section 2).

If you take more ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG than you should
If you accidentally take more tablets than you should, contact your doctor or the nearest emergency department immediately (bring the remaining tablets, the packaging, or this leaflet with you if possible). The most common symptoms and signs of overdose include low blood pressure with fainting (hypotension), very slow heartbeat (bradycardia), changes in blood chemistry (electrolytes), kidney dysfunction, excessive urination leading to dehydration, nausea and drowsiness, muscle spasms, and disturbances in heart rhythm (particularly if you are taking digitalis or other medicines for heart rhythm problems).

If you forget to take ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG
If you forget to take a dose, take it 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 regular time. Do not take a double dose to make up for the forgotten tablet.

If you stop taking ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG
Always consult your doctor before stopping treatment with ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported in clinical studies with zofenopril and hydrochlorothiazide:

Common side effects (may affect up to 1 in 10 people):
dizziness;
headache;
cough.

Uncommon side effects (may affect up to 1 in 100 people):
infections;
bronchitis;
sore throat;
increase in cholesterol and/or other lipids in the blood, increase in blood glucose, potassium, uric acid, creatinine, and liver enzymes;
decrease in potassium in the blood;
insomnia;
drowsiness, fainting, muscle stiffness (hypertonia);
angina, myocardial infarction, atrial fibrillation, palpitations;
hot flushes, low blood pressure, high blood pressure;
nausea, indigestion, gastritis, gum inflammation, dry mouth, stomach pain;
rapid onset of swelling, particularly of the lips, cheeks, eyelids, tongue, palate, larynx, possibly with sudden difficulty in breathing (angioedema). If you experience any of these effects, it means you have a severe allergy to ZOFENOPRIL and IDROCLOROTIAZIDE EG. You may require urgent medical attention or hospitalization;
skin disorders characterized by scaly pink areas (psoriasis), acne, dry skin, itching, urticaria;
back pain;
increased amount of urine (polyuria);
generalized weakness (asthenia), influenza-like symptoms, peripheral swelling (usually around the ankles);
impotence.

The following side effects were not reported in clinical studies with zofenopril and hydrochlorothiazide, but have been reported with zofenopril calcium and/or other ACE inhibitors, and therefore may also occur during treatment with ZOFENOPRIL and IDROCLOROTIAZIDE EG:
tiredness (fatigue). Severely low blood pressure at the start of treatment or when the dose is increased, with dizziness and visual disturbances;
chest pain, muscle pain and/or cramps;
altered consciousness, sudden dizziness, sudden blurred vision or weakness and/or loss of sensation to touch on one side of the body (transient ischemic attack or stroke);
reduced kidney function, changes in daily urine output, presence of protein in the urine (proteinuria);
vomiting, diarrhea, constipation;
allergic skin reactions with peeling, redness, blistering and skin eruptions (toxic epidermal necrolysis), worsening of psoriasis, hair loss (alopecia);
increased sweating;
mood changes, depression, sleep disorders;
abnormal skin sensations such as burning, tingling, prickling (paresthesia);
balance disorders, confusion, ringing in the ears (tinnitus), taste disturbances, blurred vision;
difficulty breathing, narrowing of the lung airways (bronchospasm), sinusitis, stuffy or runny nose (rhinitis), inflammation of the tongue (glossitis);
yellowing of the skin (jaundice), inflammation of the liver or pancreas (hepatitis, pancreatitis), intestinal obstruction (ileus);
abnormal blood test results, changes in red blood cell, white blood cell or platelet counts, or a reduction in the number of all blood cells (pancytopenia): contact your doctor if you notice you bruise easily or if you have unexplained sore throat or fever;
increased levels of bilirubin and urea in the blood;
anemia due to breakdown of red blood cells (hemolytic anemia), which may occur if you have G6PD (glucose-6-phosphate dehydrogenase) deficiency.

After the marketing of zofenopril, the following rare side effects have been reported (may affect up to 1 in 1,000 people):

  • fainting (syncope)
  • strong heartbeat, which may be rapid or irregular (palpitations)
  • hypotension
  • urticaria
  • itching
  • increased potassium levels in the blood

The following side effects were not reported in clinical studies with zofenopril and hydrochlorothiazide, but have been reported with hydrochlorothiazide, and therefore may also occur during treatment with ZOFENOPRIL and IDROCLOROTIAZIDE EG:
impaired production of new blood cells by the bone marrow (bone marrow failure);
fever, systemic allergic reaction (anaphylactic reaction);
altered body fluid levels (dehydration) and blood chemicals (electrolytes), gout, diabetes, metabolic alkalosis;
apathy, nervousness, restlessness;
seizures, decreased levels of consciousness, coma, paresis;
yellow vision (xanthopsia), worsening of myopia, decreased tear production;
rapid-onset reduction in distance vision (acute myopia), decreased vision or eye pain due to elevated pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma (frequency not known);
dizziness (sensation of spinning);
heart rhythm disorders (arrhythmias), changes in electrocardiogram;
formation of blood clots in veins (thrombosis) and embolism, circulatory collapse (shock);
respiratory distress, lung inflammation (pneumonitis), fibrous tissue formation in the lungs (interstitial lung disease), fluid accumulation in the lungs (pulmonary edema);
acute respiratory distress (symptoms include severe shortness of breath, fever, weakness, and confusion) (very rare frequency);
thirst, loss of appetite (anorexia), absence of intestinal movement (paralytic ileus), excessive gas in the stomach, inflammation of the salivary glands (sialadenitis), increased amylase in the blood (a pancreatic enzyme, hyperamylasemia), inflammation of the gallbladder (cholecystitis);
purple-colored spots on the skin (purpura), increased skin sensitivity to sunlight, rash (especially facial) and/or blotchy redness 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 fluids and waste products in the body), inflammation of the connective tissue within the kidneys (interstitial nephritis), sugar in the urine;
skin and lip cancer (non-melanoma skin cancer) (frequency not known).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton and blister after Exp. The expiry date refers to the last day of that month.
Do not dispose of any medicine 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 ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG contains
The active substances are zofenopril calcium and hydrochlorothiazide. Each film-coated tablet contains 30 mg of zofenopril calcium and 12.5 mg of hydrochlorothiazide.
The other components are:
Tablet core: microcrystalline cellulose, monohydrate lactose, pregelatinized corn starch, sodium croscarmellose, anhydrous colloidal silica, magnesium stearate.
Film coating: Opadry II Orange (polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, sunset yellow FCF aluminium lake (E110), red iron oxide (E172)).
Description of the appearance of ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG and contents of the pack
ZOFENOPRIL and HYDROCHLOROTHIAZIDE EG 30 mg/12.5 mg tablets are light red, round, film-coated tablets with a score line on one side. The score line is intended to facilitate breaking the tablet if you have difficulty swallowing it whole.
The tablets are available in packs of 28 tablets in PVC/PVDC-Al blisters.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
EG S.p.A., Via Pavia 6, 20136 Milan, Italy
Manufacturer
Bluepharma Indústria Farmacêutica S.A., S. Martinho do Bispo, 3045-016 Coimbra, Portugal