Patient Information Leaflet

Gentipress 20 mg/6 mg tablets

Enalapril maleate/Hydrochlorothiazide
Please read all of 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 only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Gentipress is and what it is used for
What you need to know before taking Gentipress
How to take Gentipress
Possible side effects
How to store Gentipress
Contents of the pack and other information

1. What Gentipress is and what it is used for

Gentipress contains two active substances: enalapril maleate and hydrochlorothiazide.
Enalapril maleate belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (ACE-inhibitors). ACE-inhibitors work by dilating blood vessels, making it easier for the heart to pump blood around the body. ACE-inhibitors are used to treat high blood pressure (hypertension).
Hydrochlorothiazide is a diuretic and belongs to a group of medicines called thiazides. It works by stimulating the kidneys to produce more urine, thereby reducing blood pressure.
Your doctor has prescribed Gentipress for the treatment of high blood pressure (hypertension), in cases where an ACE-inhibitor alone is not sufficient to adequately control it.

2. What you should know before taking Gentipress

Do not take Gentipress if:

you are allergic to the active substances (enalapril maleate and hydrochlorothiazide) or to other sulfonamide-derived medicines (a chemically related substance to hydrochlorothiazide; ask your doctor if you are unsure about what sulfonamide-derived medicines are), or to any of the other ingredients of this medicine (listed in section 6);
you have previously experienced, after taking ACE inhibitors, a hypersensitivity reaction (allergic reaction) causing a rash similar to hives, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat, resulting in difficulty swallowing or breathing (angioedema);
you suffer from hereditary angioedema (due to a familial predisposition), a very rare but serious genetic disease that may cause sudden swelling of the face, arms, legs, hands, feet, genitals, digestive tract, and respiratory pathways;
you suffer from idiopathic angioedema, i.e. angioedema of unknown cause;
you are not producing urine (anuria);
you have severe kidney problems (severe renal failure);
you have severe liver problems (severe hepatic impairment);
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
you are in the second or third trimester of pregnancy (see section “Pregnancy and breastfeeding”);
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, for example in the throat);
you are currently taking any of the following medicines, as 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 or pharmacist before taking Gentipress if:

you are at risk of excessively low blood pressure (hypotension – you may notice this as a feeling of faintness or dizziness, especially when standing), due to concomitant loss of salts and/or fluids, for example because you are taking medicines that increase urine production (diuretics), or are on a low-salt diet, or following vomiting or diarrhoea, resulting in electrolyte imbalance. In such cases, your doctor will advise you to have regular blood tests to monitor your electrolyte levels. A significant drop in blood pressure can be dangerous, particularly in patients with heart blood flow disorders (ischaemic heart disease) or brain blood flow disorders (ischaemic cerebrovascular disease). Hypotension has been observed in patients with heart problems, with or without kidney involvement;
you are at risk of increased potassium levels in the blood (hyperkalaemia) due to:
kidney failure, worsening kidney function, age over 70 years, diabetes, dehydration, acute heart failure causing inadequate blood pumping by the heart, increased blood acid levels (metabolic acidosis);
concomitant use of medicines that increase urine output while preserving potassium (potassium-sparing diuretics, e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or if you are taking other medicines that may affect blood potassium levels, such as heparin (an anticoagulant) (see section “Other medicines and Gentipress”). If your doctor considers it appropriate to use Gentipress with these medicines, you will be asked to undergo periodic checks to assess your blood potassium levels;
you are taking lithium (a medicine for treating psychiatric disorders – see section “Other medicines and Gentipress”);
you have narrowing (stenosis) of the aortic artery or thickening of the heart walls (hypertrophic cardiomyopathy);
you have severe heart problems, as renal failure has been reported in such cases following treatment with Gentipress;
you have kidney problems or narrowing (stenosis) of one or both renal arteries, as there is an increased risk of hypotension and renal failure. In such cases, your doctor will closely monitor your kidney function;
you have recently undergone a kidney transplant;
you are undergoing dialysis (blood purification therapy) due to renal failure;
you have a connective tissue disease affecting blood vessels, for example systemic lupus erythematosus, rheumatoid arthritis or scleroderma, are taking medicines that suppress the immune system (immunosuppressants), suffer from gout or are taking allopurinol (used in the treatment of gout) or procainamide (used to treat heart rhythm disorders), or have a combination of these risk factors. In some cases, severe infections that do not respond to antibiotic therapy have occurred. If you need to take Gentipress, inform your doctor of any signs or symptoms of infection;
you suffer from a disorder called systemic lupus erythematosus (an autoimmune disease causing skin inflammation), which may develop or worsen with the use of Gentipress;
you have diabetes and are taking oral antidiabetic medicines or insulin. In this case, your doctor will advise you to have blood tests to monitor your glucose levels, particularly during the first month of treatment with Gentipress, and will assess whether the dose of your antidiabetic medicines needs adjustment;
you have previously experienced a hypersensitivity reaction (allergic reaction) causing a rash similar to hives, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat, resulting in difficulty swallowing or breathing (angioedema);
you have a history of allergy or bronchial asthma, as sensitivity reactions may occur with the use of Gentipress;
you are of Black race. Gentipress may indeed be less effective in lowering blood pressure in Black patients compared to non-Black patients. In addition, you may have a higher risk of developing angioedema;
you have liver problems or suffer from a disease that could lead to destruction of liver cells (progressive hepatopathy);
you have chronic degenerative liver disease (hepatic cirrhosis), produce large amounts of urine, do not take an adequate amount of electrolytes orally, or are being treated with corticosteroids or adrenocorticotropic hormone (ACTH) (see section “Other medicines and Gentipress”), as in these cases the risk of low blood potassium levels (hypokalaemia) is high;
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 eye pressure, and may occur from a few hours to several weeks after taking Gentipress. If untreated, they may lead to permanent vision loss. If you have previously been allergic to penicillin or a sulfonamide, you may be at higher risk of developing this condition;
you have previously had skin cancer or are developing 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 sun exposure and UV rays while taking Gentipress;
you are taking any of the following medicines used to treat 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.

Your doctor may check your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.
See also the information under the heading "Do not take Gentipress".
Stop treatment with Gentipress and inform your doctor immediately if you experience:

yellowing of the skin or whites of the eyes (jaundice), indicating liver problems or increased levels of transaminases (liver enzymes) in the blood;
a rash similar to hives, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat, resulting in difficulty swallowing or breathing (angioedema).

Inform your doctor if you experience:

symptoms of electrolyte imbalance, which may include dry mouth (xerostomia), thirst, weakness (asthenia), pathological state of deep sleep (lethargy), drowsiness, restlessness, muscle pain or cramps, muscle fatigue, low blood pressure (hypotension), reduced urine output (oliguria), increased heart rate (tachycardia), and gastrointestinal disturbances such as nausea and vomiting;
increased levels of nitrogen and creatinine in the blood, which may suggest possible renal artery stenosis. Your doctor may advise you to stop taking Gentipress.

If you are taking Gentipress, inform your doctor if:

you are scheduled for general anaesthesia and/or major surgery;
you are scheduled for treatment to reduce the effects of an allergy, for example following an insect sting (desensitisation treatment). If you take Gentipress during this treatment, you may experience a severe allergic reaction; therefore, it is advisable to temporarily interrupt therapy;
you are scheduled for a treatment called LDL (low-density lipoprotein) apheresis, to remove cholesterol from the blood using machines. Your doctor may advise you to stop taking Gentipress to prevent a possible allergic reaction;
you have developed a persistent dry cough over a long period after starting treatment with an ACE inhibitor;
you need to undergo tests to assess parathyroid gland function. Your doctor may advise you to stop taking Gentipress before undergoing this test.

Children and adolescents
The use of Gentipress is not recommended in children under 18 years of age due to lack of safety and efficacy data.
Other medicines and Gentipress
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your doctor may need to adjust your dose and/or take other precautions.
For your doctor to prescribe the correct dose of Gentipress, it is particularly important that they know if you are taking any of the following medicines:

potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase blood potassium levels (such as trimethoprim and cotrimoxazole for treating bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent clotting);
an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also information under “Do not take Gentipress” and “Warnings and precautions”);
other medicines that lower blood pressure (antihypertensives), including vasodilators, nitroglycerin, and other nitrates (substances that dilate blood vessels);
lithium (used to treat manic-depressive psychosis or bipolar disorder);
medicines used to treat stiffness and inflammation associated with painful conditions, particularly those affecting muscles, bones and joints, including:
gold-containing medicines administered by injection, e.g. sodium aurothiomalate, which may cause facial flushing, nausea, vomiting, and low blood pressure when taken with Gentipress;
non-steroidal anti-inflammatory drugs (NSAIDs), which may impair proper blood pressure control and increase blood potassium levels;
medicines that increase urine output while preserving potassium (potassium-sparing diuretics, e.g. spironolactone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, and medicines that may increase blood potassium levels, such as heparin;
medicines that increase urine production by the kidneys (diuretics), such as thiazides or loop diuretics;
antipsychotics and tricyclic antidepressants, used to treat mental disorders;
anaesthetics;
medicines acting on the autonomic nervous system (sympathomimetics), such as those used to treat certain heart and vascular diseases and some cold medicines;
insulin or other oral antidiabetic medicines. Blood glucose levels should be closely monitored during the first weeks of treatment with Gentipress, especially in patients with kidney problems;
barbiturates, which have a sedative effect on the central nervous system, used, for example, to treat epilepsy;
analgesic medicines with anaesthetic effects (e.g. opioids);
medicines used to reduce blood fat levels, such as cholestyramine and colestipol resins;
medicines used to treat irregular heartbeat (antiarrhythmics such as quinidine, procainamide, amiodarone, sotalol);
medicines used to treat heart failure (digitalis medicines);
corticosteroids (which modulate anti-inflammatory responses);
excessive use of laxatives;
cancer medicines such as cyclophosphamide or methotrexate;
medicines used to treat gout, such as allopurinol;
medicines that suppress the immune system (immunosuppressants).

Gentipress with food, drinks and alcohol
Gentipress should not be taken with alcohol, as this may increase the hypotensive effects of Gentipress.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Gentipress before becoming pregnant or as soon as you find out you are pregnant, and will recommend an alternative medicine.
Gentipress is not recommended during pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. Gentipress is not recommended for breastfeeding mothers, especially if your baby is a newborn or premature.
Driving and using machines
Individual responses to medicines may vary. Some of the adverse effects reported with Gentipress may impair the ability of some patients to drive or operate machinery (see section “Possible side effects”). Therefore, exercise caution when driving or operating machinery.
Gentipress contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Gentipress contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free.”
For those engaged in sports
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Gentipress

Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
Your doctor will decide the correct dose for you, taking into account your condition and whether you are taking other medicines.
The recommended dose is one tablet once daily, taken with a glass of water, if necessary.
If you are taking another medicine that promotes diuresis, your doctor may instruct you to stop taking the diuretic 2 or 3 days before starting treatment with Gentipress, in order to avoid excessive lowering of blood pressure during the initial phase of treatment.

Use in children and adolescents
The use of Gentipress is not recommended in children under 18 years of age.

Patients with kidney problems
If you have kidney problems, your doctor will monitor your kidney function and adjust the dose of Gentipress accordingly.
The use of Gentipress as initial therapy in patients with mild renal impairment (creatinine clearance greater than 30 ml/min up to 80 ml/min) is not recommended.
Gentipress must not be used in patients with severe kidney problems (creatinine clearance less than or equal to 30 ml/min).

If you take more Gentipress than you should
In case of accidental ingestion or overdose of Gentipress, contact your doctor immediately or go to the nearest hospital.
The most likely symptoms of an overdose are dizziness or lightheadedness due to a sudden or excessive drop in blood pressure, excessive thirst, cough, confusion, shortness of breath, anxiety, reduced urine output, or fast or slow heartbeat.

If you forget to take Gentipress
Take Gentipress as your doctor has instructed. Do not take a double dose to make up for the missed tablet. Simply continue as prescribed.

If you stop taking Gentipress
Do not stop treatment with Gentipress unless your doctor tells you to.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop treatment with Gentipress and consult your doctor immediately if you experience:

symptoms of angioedema, such as a rash similar to hives, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat, leading to difficulty swallowing or breathing;
yellowing of the skin and whites of the eyes (jaundice), indicating liver problems or an increase in transaminase levels (liver enzymes) in the blood.

Listed below are the side effects reported with the use of Gentipress:
Very common (may affect more than 1 in 10 people)

blurred vision;
dizziness;
cough;
feeling unwell (nausea);
weakness (asthenia).

Common (may affect up to 1 in 10 people)

low blood potassium levels (hypokalaemia), increased blood cholesterol or fat (triglycerides) levels, increased blood uric acid levels (hyperuricaemia);
headache (cephalalgia), depression, temporary loss of consciousness (syncope), altered taste;
light-headedness due to low blood pressure, including sudden drop in blood pressure when standing up quickly (orthostatic hypotension), changes in heart rhythm, chest pain with a sensation of tightness, pressure or heaviness (angina pectoris), rapid heartbeat (tachycardia);
shortness of breath (dyspnoea);
diarrhoea, abdominal pain;
skin rash (exanthema);
involuntary muscle contractions (muscle cramps);
chest pain, tiredness (fatigability);
increased blood potassium levels (hyperkalaemia), increased blood creatinine levels.

Uncommon (may affect up to 1 in 100 people)

decrease in the number of red blood cells (including aplastic and haemolytic anaemia);
low blood sugar levels (hypoglycaemia), low blood magnesium levels (hypomagnesaemia), disease with painful and swollen joints caused by uric acid crystals (gout);
confusion, drowsiness, insomnia, nervousness, unexplained tingling (paraesthesia), sensation of dizziness (vertigo), reduced sexual desire;
unpleasant sensation of ringing or buzzing in the ears (tinnitus);
facial redness (flushing), rapid or irregular heartbeat (palpitations), heart attack (myocardial infarction) or stroke (cerebrovascular accident), possibly due to excessively low blood pressure in high-risk patients (patients with impaired blood flow to the heart and/or brain – see section “Warnings and precautions”);
nasal discharge (rhinorrhoea), sore throat (laryngodynia) and hoarseness, asthma associated with chest tightness (bronchospasm/asthma);
reduced intestinal movements (ileus), inflammation of the pancreas (pancreatitis), vomiting, pain in the upper middle part of the abdomen (dyspepsia), constipation (stipsis), loss of appetite (anorexia), stomach irritation, dry mouth, activation of lesions in the digestive tract mucosa (peptic ulcer), excess gas in the stomach or intestines (flatulence);
increased sweating (diaphoresis), itching, urticaria, hair loss (alopecia);
joint pain (arthralgia);
kidney problems (renal dysfunction), kidney failure, presence of protein in the urine (proteinuria);
difficulty in men to achieve or maintain an erection (impotence);
weakness (malaise), fever;
increased blood urea levels (uraemia), low sodium concentration in the blood (hyponatraemia).

Rare (may affect up to 1 in 1,000 people)

decrease in the number of certain types of white blood cells (neutropenia, leucopenia and agranulocytosis), haemoglobin levels, total volume of red blood cells (low haematocrit), blood platelets (thrombocytopenia), or all types of blood cells (pancytopenia), bone marrow suppression (when the bone marrow fails to produce enough blood cells), swollen glands (lymphadenopathy), diseases in which the immune system produces antibodies that attack the body's own organs and tissues (autoimmune diseases);
increased blood sugar levels;
dream abnormalities, sleep disturbances, muscle weakness sometimes due to low potassium levels (paresis);
reduced blood flow to fingers of hands and feet causing redness and pain (Raynaud's phenomenon);
radiological lung abnormalities (pulmonary infiltrates); severe respiratory failure (respiratory distress syndrome), including inflammation (pneumonitis) and fluid accumulation in the lungs (pulmonary oedema), irritation or inflammation of the nose (rhinitis), allergic reaction (hypersensitivity) in the lungs (allergic alveolitis), lung disease (eosinophilic pneumonia);
inflammation of mucosal linings (stomatitis) or oral cavity ulcerations (aphthous ulcers), inflammation of the tongue (glossitis);
liver failure, liver damage (hepatic necrosis, potentially fatal), inflammation of the liver or bile ducts (hepatocellular or cholestatic hepatitis), yellowing of the skin and whites of the eyes (jaundice), inflammation of the gallbladder (cholecystitis, particularly in patients with pre-existing gallstones);
severe hypersensitivity reaction with high fever, appearance of red patches on the skin (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), severe skin rash with skin and hair loss (exfoliative dermatitis), cutaneous lupus erythematosus (an autoimmune disease causing skin inflammation), redness of the skin with peeling (erythroderma), appearance of small fluid-filled blisters on the skin (pemphigus);
reduced urine output (oliguria), kidney disease (interstitial nephritis);
breast enlargement in men (gynaecomastia);
increased liver enzymes, increased blood bilirubin levels (bilirubinaemia).

Very rare (may affect up to 1 in 10,000 people)

increased blood calcium levels (hypercalcaemia);
swelling of the intestinal mucosa (intestinal angioedema).

Not known (frequency cannot be estimated from the available data):

excessive release of antidiuretic hormone, which may cause headache, nausea and malaise (syndrome of inappropriate antidiuretic hormone secretion, SIADH);
decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion));
cancer of the skin and lips (non-melanoma skin cancer).

Other side effects
A complex disorder including one or more of the following symptoms has been reported:

fever, inflammation of the membranes lining body cavities such as chest and abdomen (serositis), inflammation of blood vessels (vasculitis), muscle pain or muscle inflammation (myalgia/myositis), joint pain or joint inflammation (arthralgia/arthritis), positive test for antinuclear antibodies, increased erythrocyte sedimentation rate (ESR), increased number of white blood cells (eosinophilia and leucocytosis), skin rash, skin sensitivity to light (photosensitivity), and other skin problems.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet,
please talk to your doctor or pharmacist. You can also report side effects directly
via the website 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 Gentipress

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the wording “Exp”. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Store in the original packaging.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Gentipress contains

The active substances are enalapril maleate and hydrochlorothiazide. Each tablet contains 20 mg of enalapril maleate and 6 mg of hydrochlorothiazide;
The other components are sodium bicarbonate, lactose monohydrate, maize starch, pregelatinized starch, indigotine (E132), magnesium stearate.

Description of the appearance of Gentipress and contents of the pack
Gentipress tablets are blue, rounded triangular-shaped tablets, with "734" engraved on one side and a triangle on the other, packed in aluminum blisters with PVC laminate containing 10, 14, 28, 30, 50, 56, 98, 100 or 300 tablets, or in single-dose aluminum blisters containing 28 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan, Italy

Manufacturer
Doppel Farmaceutici S.r.l
Via Volturno, 48 - Quinto de’ Stampi
20089 Rozzano (Milan), Italy