Zoprazide

PACKAGE LEAFLET: INFORMATION FOR THE USER

ZOPRAZIDE 30mg/12.5mg film-coated tablets

(Zofenopril calcium/hydrochlorothiazide)
Please read this leaflet carefully before 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. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. WHAT ZOPRAZIDE IS AND WHAT IT IS USED FOR

Zoprazide 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. Zoprazide is used to treat mild to moderate high blood pressure (hypertension) when it cannot be controlled by taking zofenopril alone.

2. WHAT YOU NEED TO KNOW BEFORE TAKING ZOPRAZIDE

Do not take Zoprazide if:

• you are beyond the third month of pregnancy (it is best to avoid taking Zoprazide even in the early stages of pregnancy – see section “Pregnancy”).
• you are allergic to calcium zofenopril or hydrochlorothiazide or to any of the excipients contained in the product (see section 6).
• you are allergic to other sulfonamide-derived substances (such as hydrochlorothiazide, which is a sulfonamide-derived product).
• you have previously experienced allergic reactions to another ACE inhibitor such as captopril or enalapril.
• 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).
• you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a type of chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, for example in the throat).
• you suffer from severe liver or kidney problems.
• you have narrowing of the arteries supplying the kidneys.
• you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Warnings and precautions
Talk to your doctor or pharmacist before taking Zoprazide.
Tell your doctor if:

• you have problems with your liver or kidneys.
• you have high blood pressure due to a kidney problem or narrowing of the artery leading to 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) or low levels of the hormone aldosterone in your blood (hypoaldosteronism).
• you have narrowing of a heart valve (aortic stenosis) or thickening of the heart walls (hypertrophic cardiomyopathy).
• you currently suffer from or have previously suffered from psoriasis (a skin condition characterized by scaly pink patches).
• you are undergoing desensitization treatment (“allergy shots”) for insect stings.
• you suffer from systemic lupus erythematosus (an autoimmune disorder, i.e., 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 help heart pumping).
• 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 medicines for high blood pressure:
  • 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, as the risk of angioedema may be increased:
  • Racecadotril, a medicine used to treat diarrhea;
  • Medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus);
  • Vildagliptin, a medicine used to treat diabetes.
• you have previously had skin cancer or are developing unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV radiation while taking Zoprazide.
• you experience vision disturbances or eye pain. These could 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 Zoprazide. If untreated, this increase may lead to permanent vision loss. Your risk may be higher if you have previously been allergic to penicillin or sulfonamides.

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 Zoprazide”.
The hydrochlorothiazide contained in Zoprazide may cause increased skin sensitivity to sunlight or artificial UV radiation. Discontinue Zoprazide and inform your doctor if you develop a rash, itching, or skin sensitivity during treatment (see also section 4).
Anti-doping tests: Zoprazide may cause positive results in anti-doping tests.
If your blood pressure becomes too low during treatment with Zoprazide, especially after the first dose (this is more likely if you are also taking other diuretics, are dehydrated, follow a low-salt diet, or have an illness or diarrhea), contact your doctor immediately, then lie down on your back (see also section 4).
If you are scheduled for surgery, inform your anesthetist that you are taking Zoprazide before receiving anesthesia. This will help the anesthetist manage your blood pressure and heart rate during the procedure.
Inform your doctor if you think you are (or might be) pregnant. The use of Zoprazide is not recommended during early pregnancy and must not be taken beyond the third month of pregnancy, as the drug may cause serious harm to your baby if used at this stage (see section “Pregnancy”).

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

Other medicines and Zoprazide
Inform your doctor or pharmacist 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 potassium levels in the blood (such as trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent transplant rejection; and heparin, a medicine used to thin the blood and prevent clotting).
• Other medicines that affect 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).
• Anesthetics.
• Narcotic drugs (such as morphine).
• Antipsychotic medicines (used to treat schizophrenia and similar conditions).
• Tricyclic antidepressants, e.g., amitriptyline and clomipramine.
• Barbiturates (used to treat anxiety, insomnia, and seizure disorders).
• Other medicines for high blood pressure and vasodilators (including beta-blockers, alpha-blockers, and diuretics such as hydrochlorothiazide, furosemide, torasemide). 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 “Do not take Zoprazide” and “Warnings and precautions”).
• Nitroglycerin and other nitrates used for chest pain (angina).
• Antacids including cimetidine (used to treat heartburn and stomach ulcers).
• Cyclosporine (used after organ transplantation) and other immunosuppressants (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 drugs (drugs acting on the nervous system, including some used to treat asthma, hay fever, and pressor amines such as adrenaline).
• Calcium salts.
• Digitalis (used to help heart pumping).
• Cholestyramine and colestipol resins (used to lower cholesterol).
• Muscle relaxants (e.g., tubocurarine).
• Amantadine (an antiviral drug).
• Racecadotril (a medicine used to treat diarrhea), medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus), and vildagliptin (a medicine used to treat diabetes). The risk of angioedema may be increased.

Zoprazide with food, drinks, and alcohol
Zoprazide can be taken with or without food, but always with water.
Alcohol enhances the blood pressure-lowering (hypotensive) effect of Zoprazide; consult your doctor for further advice on alcohol consumption while taking this medicine.

Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine. Your doctor will usually advise you to stop taking Zoprazide before pregnancy or as soon as pregnancy is confirmed and will recommend an alternative medicine. Zoprazide is not recommended during early pregnancy and must not be taken beyond the third month of pregnancy, as the drug may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding
If you are breastfeeding or planning to breastfeed, consult your doctor before taking this medicine. Zoprazide is not recommended for breastfeeding mothers, and your doctor may choose another suitable medicine if you wish to continue breastfeeding, especially if you are nursing a newborn or a premature infant.

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

Zoprazide contains lactose
This product contains lactose. If you know you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. HOW TO TAKE ZOPRAZIDE

Always take Zoprazide exactly as instructed by your doctor. If you have any doubts, consult your doctor.
The recommended dose of Zoprazide is one tablet per day.
Zoprazide may be taken with food or on an empty stomach. It is preferable to take the tablet with water.
The break line is only intended to help you divide the tablet if you have difficulty swallowing it whole.
If you are over 65 years old and have impaired kidney function, Zoprazide may not be the appropriate medicine for you (see section 2 – “Warnings and precautions”).

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

If you take more Zoprazide than you should
If you accidentally take more tablets than you should, contact your doctor or the nearest emergency department immediately (take 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 heart rate (bradycardia), disturbances in blood chemistry (electrolytes), kidney dysfunction, excessive urination leading to dehydration, nausea and drowsiness, muscle spasms, and heart rhythm disorders (especially if you are taking digitalis or other medicines for heart rhythm problems).

If you forget to take Zoprazide
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next 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 missed tablet.

If you stop taking Zoprazide
Always consult your doctor before stopping treatment with Zoprazide.
If you have any questions about the use of Zoprazide, ask your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Zoprazide may cause adverse reactions, although not everyone experiences them.
The following adverse reactions have been reported in clinical studies conducted with Zoprazide:

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

• dizziness
• headache
• cough

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

• rapid onset of swelling, particularly of the lips, cheeks, eyelids, tongue, palate, larynx, possibly with sudden breathing difficulty (angioedema). If you experience any of these symptoms, it means you have a severe allergy to Zoprazide. You may require urgent medical treatment or hospitalization
• infections
• bronchitis
• sore throat
• increased cholesterol and/or other lipids in the blood, increased blood glucose, potassium, uric acid, creatinine, and liver enzymes
• decreased 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
• skin disorders characterized by scaly pink areas (psoriasis), acne, dry skin, itching, urticaria
• back pain
• increased urine output (polyuria)
• generalized weakness (asthenia), influenza-like symptoms, peripheral swelling (usually around the ankles)
• impotence

The following side effects have not been reported in clinical studies with Zoprazide, but have been reported with zofenopril calcium and/or other ACE inhibitors, and therefore may also occur with the use of Zoprazide:

• Fatigue. Severely low blood pressure at the start of treatment or when the dose is increased, with dizziness, visual disturbances, fainting; low blood pressure in the upright position.
• Chest pain, muscle pain and/or cramps
• Altered mental status, sudden dizziness, sudden blurred vision or weakness and/or loss of sensation 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
• Altered 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)
• Blood test abnormalities, 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 easy bruising or 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

The following side effects have not been reported in clinical studies with Zoprazide, but have been reported with hydrochlorothiazide, and therefore may also occur with the use of Zoprazide:

• Altered production of new blood cells by the bone marrow (bone marrow failure)
• Fever, systemic allergic reaction (anaphylactic reaction)
• Altered levels of body fluids (dehydration) and blood chemicals (electrolytes), gout, diabetes, metabolic alkalosis
• Apathy, nervousness, agitation
• Seizures, decreased level of consciousness, coma, paresis
• Yellow vision (xanthopsia), worsening of myopia, decreased tear production, 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)
• Dizziness (sensation of spinning)
• Heart rhythm disorders (arrhythmias), changes in electrocardiogram
• Blood clot formation in veins (thrombosis) and embolism, circulatory collapse (shock)
• Respiratory distress, lung inflammation (pneumonia), fibrous tissue formation in the lungs (interstitial lung disease), fluid accumulation in the lungs (pulmonary edema)
• 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), gallbladder inflammation (cholecystitis)
• Purple-colored spots on the skin (purpura), increased skin sensitivity to sunlight, rash (especially facial) and/or patchy 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 increased fluid and waste products in the body), inflammation of the connective tissue within the kidneys (interstitial nephritis), sugar in the urine
• Frequency “not known”: skin and lip cancer (non-melanoma skin cancer)

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

5. HOW TO STORE ZOPRAZIDE

Keep this medicine out of the sight and reach of children.
Do not store Zoprazide above 30°C.
Do not use this medicine after the expiry date stated on the outer carton and blister after "Exp". The expiry date refers to the last day of the month indicated.
Always keep the tablets in the original packaging.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What Zoprazide contains
The active substances are zofenopril calcium 30 mg and hydrochlorothiazide 12.5 mg.
The other components are:

• Tablet core: microcrystalline cellulose, monohydrate lactose, maize starch, hypromellose, anhydrous colloidal silica, magnesium stearate. Coating: Opadry Pink 02B24436 (composed of hypromellose, titanium dioxide (E 171), polyethylene glycol 400, iron oxide red (E 172)), polyethylene glycol 6000 (see section 2 “Zoprazide contains lactose”)

Description of the appearance of Zoprazide and packaging contents
Zoprazide 30 mg/12.5 mg tablets are pastel red, round, slightly biconvex, film-coated tablets with a break line on one side. The score line on the tablet is intended to facilitate breaking the tablet for easier swallowing and is not intended to divide the tablet into equal doses. The tablets are available in packages containing 14, 28, 30, 50, 56, 90 or 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Laboratori Guidotti S.p.A. – Via Livornese, 897 – Pisa – La Vettola
Sales Licensee: A. Menarini Industrie Farmaceutiche Riunite s.r.l., Via Sette Santi, 3 - Florence
Manufacturer
A. MENARINI Manufacturing Logistics and Services Srl
Campo di Pile, L'Aquila - Italy.
Menarini –Von Heyden GmbH
Leipziger Strasse 7-13,
01097 – Dresden (Germany).

This medicinal product is authorized in the EEA Member States under the following names:
Belgium: Zopranol Plus
France: Coteoula
Greece: Zopranol-Plus
Italy: Zoprazide
Luxembourg: Zofenil Plus
Portugal: Zopranol Plus
Netherlands: Zopranol HCTZ