GENTIPRESS Tablet

Зміст інструкції

1. Gentipress 20 mg/6 mg tablets
   1. What is Gentipress and what is it used for
   2. What you need to know before taking Gentipress
   3. How to take Gentipress
   4. Possible side effects
   5. How to store Gentipress
   6. Contents of the pack and other information

Gentipress 20 mg/6 mg tablets

Enalapril maleate/Hydrochlorothiazide

Read this leaflet carefully before you start taking this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Gentipress and what is it used for

Gentipress contains two active ingredients: enalapril maleate and hydrochlorothiazide.
Enalapril maleate belongs to a group of medicines known as angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors work by dilating blood vessels to make it easier for the heart to pump blood to all parts of the body. ACE inhibitors are used for the treatment of 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 a greater amount of urine and thereby reducing blood pressure.
Your doctor has prescribed Gentipress for the treatment of high blood pressure (hypertension), where an ACE inhibitor alone is not sufficient to control it adequately.

2. What you need to know before taking Gentipress

Do not take Gentipress if:

• you are allergic to the active ingredients (enalapril maleate and hydrochlorothiazide) or to other medicines derived from sulfonamides (a substance chemically related to hydrochlorothiazide, ask your doctor if you are not sure what sulfonamide-derived medicines are), or to any of the other ingredients of this medicine (listed in section 6);
• you have, after taking ACE inhibitors, experienced a hypersensitivity reaction (allergic reaction) that caused skin rash, similar to urticaria, 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 family history), a very rare but serious genetic condition that can cause sudden swelling of the face, arms, legs, hands, feet, genitals, digestive tract and airways;
• you suffer from idiopathic angioedema, that is, angioedema whose cause is unknown;
• you do not produce urine (anuria);
• you suffer from severe kidney problems (severe renal failure);
• you suffer from severe liver problems (severe hepatic impairment);
• you suffer from diabetes or your kidney function is impaired and you are being treated with a medicine that lowers blood pressure, containing aliskiren;
• you are in the second or third trimester of pregnancy (see section “Pregnancy and breastfeeding”);
• you have taken or are taking sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin in areas such as the throat);
• 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 organ rejection after transplantation 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 an excessive drop in blood pressure (hypotension - you notice this when you have a feeling of fainting or dizziness, especially when standing up) due to concomitant loss of salts and/or fluids, for example because you are taking medicines that increase urine production (diuretics) or are following a low-salt diet, or following vomiting or diarrhoea, resulting in electrolyte imbalance. In such cases, your doctor will advise you to regularly measure the amount of electrolytes in your blood. An excessive drop in blood pressure can be dangerous, especially in patients with impaired blood flow to the heart (ischaemic heart disease) or brain (ischaemic cerebrovascular disease). Hypotension has been observed in the presence of heart problems, associated or not with kidney problems;
• you are at risk of an increase in blood potassium levels (hyperkalaemia) due to:
• renal failure, worsening of kidney function, age over 70 years, diabetes, dehydration, acute heart failure due to the heart not pumping blood adequately throughout the body, increased acidity in the blood (metabolic acidosis);
• concomitant use of medicines that facilitate urine excretion while preserving potassium (potassium-sparing diuretics, for example spironolactone, eplerenone, triamterene or amiloride), potassium supplements or salt substitutes containing potassium, or if you are taking other medicines that can affect blood potassium levels, such as heparin (an anticoagulant) (see section “Other medicines and Gentipress”). If your doctor deems it appropriate to use Gentipress with the aforementioned medicines, they will ask you to undergo periodic checks to assess your blood potassium levels;
• you are taking lithium (medicine for the treatment of psychiatric disorders - see section “Other medicines and Gentipress”);
• you suffer from a narrowing (stenosis) of the aortic artery or have a thickening of the heart walls (hypertrophic cardiomyopathy);
• you suffer from severe heart problems, as in such cases renal failure has been reported following treatment with Gentipress;
• you have kidney problems or have a 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 keep you under close observation, monitoring your kidney function;
• you have recently had a kidney transplant;
• you are undergoing dialysis (blood purification therapy) due to renal failure;
• you suffer from a connective tissue disease involving blood vessels, for example lupus erythematosus, rheumatoid arthritis or scleroderma, are taking medicines that

suppress the immune defenses (immunosuppressants), suffer from gout or are taking allopurinol (used in the treatment of gout) or procainamide (used to treat heart rhythm abnormalities), or have a combination of these risk factors. In some cases, serious infections have occurred that did not respond to antibiotic therapy. If you need to take Gentipress, tell your doctor about any signs or symptoms of infection;

• you suffer from a condition called systemic lupus erythematosus (an autoimmune disease that causes skin inflammation), which may occur or worsen with the use of Gentipress;
• you have diabetes and are taking oral antidiabetic medicines or insulin. In such cases, your doctor will tell you to have blood tests to check your blood glucose levels, especially during the first month of treatment with Gentipress, and will assess the need to adjust the dose of your antidiabetic medicines;
• you have ever had a hypersensitivity reaction (allergic reaction) that caused skin rash, similar to urticaria, 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 in fact be less effective in lowering blood pressure in patients of black race compared to patients of non-black race. 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 and degenerative liver disease (liver cirrhosis), have a marked production of urine, do not take an adequate amount of electrolytes orally, are being treated with corticosteroids or adrenocorticotropic hormone ACTH (see section “Other medicines and Gentipress”), as in such cases the risk of a decrease in blood potassium levels (hypokalaemia) is high;
• you have a decrease in vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in pressure in the eye and can occur within a period ranging from a few hours to weeks after taking Gentipress. If left untreated, they can lead to permanent vision loss. If you have previously had an allergy to penicillin or a sulfonamide, you may be at higher risk of developing this condition;
• you have had skin cancer in the past or if you are developing an unexpected skin lesion during treatment. Long-term use of hydrochlorothiazide, especially at high doses, may increase the risk of some types of

skin cancer and lips (non-melanoma skin cancer). Protect your skin from exposure to the sun and UV rays while taking Gentipress;

• you are taking one of the following medicines used to treat high blood pressure:
• an "angiotensin II receptor blocker" (AIIRA) (also known as sartans - for example valsartan, telmisartan, irbesartan), especially if you suffer from kidney problems related to diabetes.
• aliskiren.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals. See also what is stated under "Do not take Gentipress”.

Stop taking Gentipress and tell your doctor if you experience:

• yellowing of the skin and the whites of the eyes (jaundice), which indicates liver problems or an increase in liver enzyme (transaminase) levels in the blood;
• skin rash, similar to urticaria, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat with resulting difficulty swallowing or breathing (angioedema).

Tell your doctor if you experience:

• symptoms of electrolyte imbalance, which may include dry mouth (xerostomia), thirst, weakness (asthenia), deep sleepiness (lethargy), drowsiness, agitation, muscle pain or cramps, muscle fatigue, low blood pressure (hypotension), reduced urine production (oliguria), increased heart rate (tachycardia) and gastrointestinal disturbances, such as nausea and vomiting.
• an increase in the level of nitrogen and creatinine in the blood, this circumstance may suggest a stenosis of the renal artery. Your doctor may tell you to stop taking Gentipress.

If you take Gentipress, tell your doctor if:

• you need to undergo general anesthesia and/or major surgery;
• you need to undergo treatment to reduce the effects of an allergy, resulting for example from an insect sting (desensitization treatment). If you are taking Gentipress while undergoing this treatment, you may experience a severe allergic reaction, so it is advisable to temporarily interrupt the therapy;
• you need to undergo a treatment called LDL (low-density lipoprotein) apheresis, to remove cholesterol from the blood using machinery. Your doctor may tell you to stop taking Gentipress to prevent a possible allergic reaction;
• you have developed a dry, persistent cough for a long period of time after starting treatment with an ACE inhibitor;
• you need to have tests to check the function of the parathyroid glands. Your doctor may tell 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 the lack of data on safety and efficacy.

Other medicines and Gentipress
Tell your doctor or pharmacist if you are taking, have recently taken or might
take any other medicine.
Your doctor may need to adjust the dose and/or take other precautions.
For your doctor to be able to prescribe the correct dose of Gentipress it is particularly
important that he/she knows if you are taking any of the following medicines:

• potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that could increase the amount of potassium in the blood (such as trimethoprim and cotrimoxazole for treating bacterial infections; cyclosporine, an immunosuppressant used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent blood clots);
• an angiotensin II receptor blocker (AIIRA) or aliskiren (see also what is stated under “Do not take Gentipress” and “Warnings and precautions”);
• other medicines that lower blood pressure (antihypertensives), including vasodilators, nitroglycerin and other nitrates (products that dilate blood vessels);
• lithium (used for the treatment of manic-depressive psychosis or bipolar disorder);
• medicines used for the treatment of stiffness and inflammation associated with painful conditions, particularly those affecting muscles, bones and joints, including:
• medicines containing gold administered by injection, for example sodium aurothiomalate, can cause flushing of the face, feeling unwell (nausea), vomiting and low blood pressure, if taken with Gentipress;
• non-steroidal anti-inflammatory drugs (NSAIDs) can prevent proper control of blood pressure and increase the level of potassium in the blood;
• medicines that facilitate the elimination of urine while preserving potassium (potassium-sparing diuretics, for example spironolactone, triamterene or amiloride), potassium supplements or salt substitutes containing potassium, medicines that can increase the level of potassium in the blood, such as heparin;
• medicines that increase the amount of urine produced by the kidneys (diuretics), such as thiazides or loop diuretics;
• antipsychotics and tricyclic antidepressants, for the treatment of mental disorders;
• anaesthetics;
• medicines that act on the autonomic nervous system (sympathomimetics) such as for example medicines used in the treatment of some heart and blood vessel diseases and some cold medicines);
• insulin or other antidiabetic medicines taken orally. The glucose level in the blood must be carefully monitored during the first few weeks of treatment with Gentipress, particularly in patients with kidney problems;
• barbiturates, which have a sedative effect on the central nervous system, used for example to treat epilepsy;
• analgesic medicines that have an anesthetic effect (such as opioids);
• medicines used to reduce the amount of fats in the blood, such as colestyramine and colestipol resins;
• medicines for treating irregular heartbeat (antiarrhythmics such as quinidine, procainamide, amiodarone, sotalol);
• medicines used for the treatment of heart failure (digitalis medicines);
• corticosteroids (which modulate anti-inflammatory reactions);
• excessive use of laxatives;
• medicines for the treatment of cancer such as cyclophosphamide or methotrexate;
• medicines for treating gout, such as allopurinol;
• medicines that suppress the immune defenses (immunosuppressants).

Gentipress with food, beverages and alcohol
Gentipress should not be taken together with alcohol, as an increase
in the hypotensive effects of Gentipress may occur.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you
are breastfeeding, ask your doctor or pharmacist for advice before using
this medicine.
Pregnancy
You must tell your doctor if you think you are pregnant (or if there is a possibility of
becoming pregnant). Usually your doctor will advise you to stop taking Gentipress before becoming pregnant or as soon as you find out you
are pregnant and will advise you to take another medicine instead of Gentipress.
Gentipress is not recommended during pregnancy, and must not be taken if you are
pregnant for more than 3 months, as it can cause serious harm to the baby if
taken after the third month of pregnancy.
Breastfeeding
Tell your doctor if you are breastfeeding or intend to breastfeed your baby with
breast milk. Gentipress is not recommended for mothers who are breastfeeding, in
particular if your baby is a newborn or premature.

Driving and operating machinery
Individual responses to medicines can vary. Some undesirable effects that have been
reported with Gentipress can interfere with the ability of some patients to drive
vehicles or operate machinery (see section “Possible undesirable effects”). Therefore
be cautious when driving and operating machinery.

Gentipresscontains lactose
If your doctor has diagnosed you with intolerance to certain sugars, contact him/her before
taking this medicine.

Gentipresscontains Sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which is
essentially ‘sodium-free."

For athletes
The use of the medicine without therapeutic need constitutes doping and may determine
positive results in anti-doping tests.

3. How to take Gentipress

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have any doubts, ask your doctor or pharmacist.
The doctor will decide what the right dose is for you, taking into account your illness and whether you are
taking other medicines.
The recommended dose is one tablet once a day to be taken, if necessary,
with a glass of water.
If you are taking another medicine that promotes diuresis, your doctor will tell you to
stop taking the diuretic 2 or 3 days before starting treatment with
Gentipress, in order to avoid an excessive drop in pressure in 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 check your kidney function and decide the
dose of Gentipress appropriately.
The use of Gentipress as initial therapy in patients with mild renal insufficiency (creatinine
clearance greater than 30 ml/min, up to 80 ml/min) is not recommended.
Gentipress should 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/taking of an excessive dose of Gentipress, immediately inform
your doctor or go to the nearest hospital.
The most likely symptom of an overdose is a feeling of dizziness or lightheadedness due to
a sudden or excessive decrease in blood pressure, excessive thirst, cough,
confusion, shortness of breath, anxiety, decreased urine output, or fast or slow heartbeat.

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

If you stop taking Gentipress
Do not stop treatment with Gentipress unless your doctor tells you to do so.
If you have any doubts 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 everyone will experience them.

Stop treatment with Gentipress and immediately consult your doctor if you experience:

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

Below are the side effects observed 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)

• lowering of blood potassium levels (hypokalaemia), increased levels of cholesterol or fats (triglycerides) in the blood, uric acid in the blood (hyperuricemia);
• headache, depression, temporary loss of consciousness (syncope), altered taste;
• feeling lightheaded due to low blood pressure, including a sudden drop in pressure when getting up quickly (orthostatic hypotension), changes in heart rhythm, pain accompanied by a feeling of constriction and oppression or heaviness in the chest (angina pectoris), rapid heartbeat (tachycardia);
• shortness of breath (dyspnoea);
• diarrhoea, abdominal pain;
• skin rash (exanthem);
• involuntary muscle contractions (muscle cramps);
• chest pain, fatigue;
• increased potassium levels in the blood (hyperkalaemia), increased creatinine levels in the blood.

Uncommon (may affect up to 1 in 100 people)

• decrease in the number of red blood cells (including aplastic and hemolytic anaemia);
• decrease in blood sugar levels (hypoglycaemia), decrease in magnesium levels in the blood (hypomagnesaemia), disease with painful and swollen joints caused by uric acid crystals (gout);
• confusion, drowsiness, insomnia, nervousness, tingling without cause (paraesthesia), feeling of spinning (vertigo), decreased sexual desire;
• annoying sensation of sounds or whistling in the ears (tinnitus);
• flushing of the face, 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 disturbances of blood flow to the heart and/or brain - see section “Warnings and precautions”);
• nasal secretion (rhinorrhoea), sore throat (laryngodynia) and hoarseness, asthma associated with a feeling of tightness in the chest (bronchospasm/asthma);
• reduction of intestinal movements (ileus), inflammation of the pancreas (pancreatitis), vomiting, pain in the upper abdomen (dyspepsia), constipation, loss of appetite (anorexia), irritation of the stomach, dry mouth, activation of lesions of the mucous membrane of the digestive tract (peptic ulcer), excess gas in the stomach or intestines (flatulence);
• increased sweating (diaphoresis), itching, hives, hair loss (alopecia);
• joint pain (arthralgia);
• kidney problems (renal dysfunction), kidney failure, presence of protein in the urine (proteinuria);
• difficulty in men achieving or maintaining an erection (impotence);
• weakness (malaise), fever;
• increased urea levels in the blood (uremia), low sodium concentration in the blood (hyponatraemia).

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

• decrease in the number of a certain type of white blood cells (neutropenia, leucopenia and agranulocytosis), amount of haemoglobin, total volume of red blood cells (low haematocrit), platelets (thrombocytopenia) or all different types of blood cells (pancytopenia), bone marrow depression (when the bone marrow fails to produce a sufficient number of cells found in the blood), swelling of the glands (lymphadenopathy), diseases in which the immune system produces antibodies that attack organs and tissues of the body (autoimmune diseases);
• increased blood sugar levels;
• altered dreams, sleep disorders, muscle weakness sometimes due to low potassium levels (paresis);
• reduced blood flow to the fingers of hands and feet causing redness and pain (Raynaud's phenomenon);
• radiological changes in the lungs (pulmonary infiltrates); severe respiratory failure (acute respiratory distress syndrome) including inflammation (pneumonia) 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 the lining of the mucous membranes (stomatitis) or ulcerations of the oral cavity (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 spots on the skin (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), severe skin rash with loss of skin and hair (exfoliative dermatitis), cutaneous lupus erythematosus (an autoimmune disease that causes skin inflammation), redness of the skin with scaling (erythrodermia), appearance of small blisters filled with fluid on the skin (pemphigus).
• decreased urine output (oliguria), kidney disease (interstitial nephritis);
• enlargement of the breasts in men (gynaecomastia);
• increases in liver enzymes, increased levels of bilirubin in the blood (bilirubinemia).

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

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

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

• excessive release of an antidiuretic hormone that can 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));
• skin and lip cancer (non-melanoma skin cancer).

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

• fever, inflammation of the membranes lining the body cavities such as chest and abdomen (serositis), inflammation of blood vessels (vasculitis), muscle pain or muscle inflammation (myalgia/myositis), joint pain or inflammation (arthralgia/arthritis), positive test for the presence of 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 effects, including those not listed in this leaflet,
please inform your doctor or pharmacist. You can also report side effects directly
through the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can contribute to providing 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 which is stated on the packaging after the
word “Scad”. The expiry date refers to the last day of the month.
This medicine does not require any particular storage conditions.
Store in the original packaging.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Gentipress contains

• The active ingredients are enalapril maleate and hydrochlorothiazide. Each tablet contains 20 mg of enalapril maleate and 6 mg of hydrochlorothiazide;
• The other ingredients are sodium bicarbonate, lactose hydrate, corn starch, pregelatinized starch, indigotine (E132), magnesium stearate.

Description of the appearance of Gentipress and contents of the pack
Gentipress tablets are blue with rounded edges and a triangular shape, with 734 imprinted on one side and a triangle on the other, contained in aluminum blister packs with a PVC laminate containing 10, 14, 28, 30, 50, 56, 98, 100 or 300 tablets, or in aluminum single-dose blister packs containing 28 tablets.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milano

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