Nalapres: detailed information

Package leaflet: Information for the patient

Nalapres 20 mg + 12.5 mg tablets

Lisinopril and 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 only. Do not give it to others, even if their symptoms are the same as yours, as it could 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 Nalapres is and what it is used for
What you need to know before taking Nalapres
How to take Nalapres
Possible side effects
How to store Nalapres
Contents of the pack and other information

1. What Nalapres is and what it is used for

Nalapres is a medicine that contains two active substances: lisinopril and hydrochlorothiazide.
Lisinopril is an antihypertensive agent, meaning it lowers blood pressure. It belongs to a group of medicines known as Angiotensin-Converting Enzyme (ACE) inhibitors. These medicines work by dilating blood vessels. This allows blood to flow more easily and reduces the effort required by the heart to pump blood throughout the body.
Hydrochlorothiazide is a diuretic belonging to a group of medicines called thiazides. It works by stimulating the kidneys to produce more urine, thereby reducing blood volume.
Nalapres is used for the treatment of high blood pressure (essential hypertension) in patients in whom lisinopril alone is not sufficient to adequately control blood pressure.

2. What you should know before taking Nalapres

Do not take Nalapres if:

you are allergic to the active substances lisinopril or hydrochlorothiazide, or to any of the other ingredients of this medicine (listed in section 6);
you are not passing urine (anuria);
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 of the face, lips, tongue and/or throat, leading to difficulty in swallowing or breathing (angioedema);
you have been diagnosed with a condition known as hereditary angioedema (a condition that makes you more prone to the swelling described above);
you are allergic to medicines used to treat infections (sulfonamides);
you are in the second or third trimester of pregnancy (it is best to avoid Nalapres even in the early stages of pregnancy) (see section “Pregnancy and breastfeeding”);
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
you suffer from severe kidney problems (creatinine clearance < 30 ml/min);
you suffer from severe liver problems;
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, such as in the throat);

Warnings and precautions
Talk to your doctor or pharmacist before taking Nalapres.
Pay particular attention during treatment with Nalapres if:

you are at risk of excessive drop in blood pressure due to excessive loss of salts and/or fluids, for example if you are taking medicines that increase urine production (diuretics), or are on a low-salt diet, or following vomiting or diarrhoea; you have low blood pressure (hypotension), which may manifest as weakness or lightheadedness. A significant drop in blood pressure can be dangerous, especially for patients with heart blood flow disorders (ischaemic heart disease) or brain blood flow disorders (ischaemic cerebrovascular disease);
you have narrowing (stenosis) of the aortic or mitral valve, or suffer from hypertrophic cardiomyopathy (a condition characterised by thickening of the heart muscle);
your kidney function is moderately impaired or you have narrowing (stenosis) of one or both renal arteries, are undergoing dialysis (blood purification therapy), or have had a kidney transplant;
you have liver problems or suffer from a disease that could lead to destruction of liver cells (progressive hepatopathy);
you are undergoing surgery requiring anaesthesia; you are undergoing or about to undergo treatment to reduce the effects of an allergy, such as insect stings (desensitisation treatment);
you have high blood sugar levels (diabetes); you are at risk of increased potassium levels in the blood;
you need to undergo tests to assess parathyroid gland function. Consult your doctor, who will advise you to stop taking hydrochlorothiazide before this test;
you suffer from gout, an inflammatory joint condition causing pain and swelling;
you suffer from an autoimmune disease (when the immune system produces antibodies that attack the body's own organs and tissues) causing skin inflammation (systemic lupus erythematosus);
you have high cholesterol levels and require a treatment called apheresis;
you develop a persistent dry cough for a prolonged period after starting treatment with Nalapres. Discuss this with your doctor;
you experience changes in blood cell counts (white blood cells, red blood cells, and platelets), or a significant drop in a certain type of white blood cells sensitive to infections (agranulocytosis), especially if you suffer from connective tissue disease (collagenosis) affecting blood vessels;
you are pregnant (or suspect or are planning pregnancy) or breastfeeding (see section “Pregnancy and breastfeeding”);
if you are of Black origin, you may be more likely to develop angioedema (characterised by swelling of the face, lips, tongue, throat, or sudden breathing difficulty);
you experience vision changes or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which may occur from a few hours to several weeks after taking Nalapres. If untreated, these may lead to permanent vision loss. If you previously had an allergy to penicillin or a sulfonamide, you may be at higher risk of developing this condition;
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 sun exposure and UV rays while taking Nalapres;
you are taking any of the following medicines used to treat high blood pressure:
an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan), especially 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 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.

Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals. See also information in the section “Do not take Nalapres”.
Stop taking Nalapres and inform your doctor immediately if you experience:

difficulty breathing or swallowing, possibly accompanied by swelling of the face, lips, tongue and/or throat;
swelling of the hands, feet or ankles;
severe skin itching accompanied by localised swelling.

Children and adolescents
Do not give Nalapres to children, as there is no data on its safety and efficacy.
Elderly
In clinical studies, the efficacy and tolerability of lisinopril and hydrochlorothiazide taken together were found to be the same in elderly and younger hypertensive patients.
Other medicines and Nalapres
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Do not take Nalapres with sacubitril/valsartan (a medicine for treating heart failure) due to increased risk of angioedema (rapid swelling under the skin, such as in the throat). See section “Do not take Nalapres”.
In particular, inform your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines:

substances that increase potassium levels in the blood, such as potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase blood potassium levels (such as trimethoprim and cotrimoxazole used to treat bacterial infections; ciclosporin, an immunosuppressant medicine used to prevent organ transplant rejection; heparin, a medicine used to thin the blood and prevent clot formation);
medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus). See section “Warnings and precautions”;
racecadotril, a medicine used to treat diarrhoea;
medicines that induce torsades de pointes, a dangerous type of heart rhythm disorder;
medicines for mood disorders, such as tricyclic antidepressants and antipsychotics;
cytostatic agents (used to reduce tumour growth);
medicines that promote urine elimination (diuretics);
lithium, used to treat bipolar disorder; indometacin, a medicine that helps relieve pain;
tubocurarine, a medicine used for muscle relaxation;
non-steroidal anti-inflammatory drugs (NSAIDs), used to treat joint inflammation (arthritis) or muscle pain;
calcium salts that may increase blood calcium levels;
injectable gold (used to treat rheumatoid arthritis, a chronic joint inflammation);
sympathomimetics (medicines acting mainly on the sympathetic nervous system, which controls internal organs, primarily blood circulation and the heart);
other medicines used to lower blood pressure;
cardiac glycosides (e.g. digoxin), as there may be an increased risk of toxicity;
barbiturates, which have a sedative effect on the central nervous system, used, for example, to treat epilepsy;
medicines with anaesthetic and sleep-inducing effects (narcotics);
insulin or other oral antidiabetic medicines such as vildagliptin;
amphotericin B (administered intravenously), used to treat fungal infections;
corticosteroids, such as cortisone, beclometasone, used, for example, in cases of inflammation, asthma;
carbenoxolone, used to treat gastrointestinal ulcers;
adrenocorticotropic hormone, which acts by stimulating the adrenal glands;
medicines for treating high cholesterol levels, such as colestyramine and colestipol;
sotalol (a medicine for heart rhythm disorders, antiarrhythmics);
allopurinol, used to treat gout;
adrenaline or noradrenaline, known as pressor amines;
an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also information in sections “Do not take Nalapres” and “Warnings and precautions”). Your doctor may consider it necessary to adjust the dose and/or take other precautions.

Nalapres with food, drinks and alcohol
Do not take Nalapres with alcohol, as this may increase the blood pressure-lowering effects of Nalapres.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take Nalapres during the first three months of pregnancy and later in pregnancy, as it may cause serious harm to the unborn child. If you think you are pregnant or are planning a pregnancy, inform your doctor, who may advise you to stop using Nalapres and prescribe an alternative treatment.
Do not take Nalapres while breastfeeding. Inform your doctor if you are breastfeeding or intend to breastfeed. Your doctor may prescribe an alternative treatment during breastfeeding, especially if your baby is a newborn or premature.
Driving and using machines
Nalapres may impair your ability to drive or operate machinery. This is more likely at the beginning of treatment, during dose adjustments, or when taken with alcohol. These effects depend on your individual sensitivity. If you are affected, do not drive or operate machinery.
During treatment with Nalapres, you may experience dizziness or fatigue.
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 Nalapres

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is 1 tablet daily.
If necessary, your doctor may increase the dose to 2 tablets daily, taken as a single administration.
If you are taking another medicine that promotes diuresis, your doctor will instruct you to stop taking the diuretic 2 or 3 days before starting treatment with Nalapres, in order to avoid excessive lowering of blood pressure during the initial phase of treatment.

Use in children and adolescents
The use of Nalapres is not recommended in children due to lack of data on safety and efficacy.

Use in the elderly
No dose adjustment is necessary.

Patients with renal problems
Your doctor may consider adjusting the dose.

If you take more Nalapres than you should
In case of accidental ingestion or overdose of Nalapres, contact your doctor immediately or go to the nearest hospital, where you will receive treatments aimed at removing the medicine from your body.
Treatment in case of overdose with Nalapres is directed at managing symptoms caused by excessive intake. These include: low blood pressure, decreased levels of potassium, sodium, and chloride in the blood, and dehydration.

If you forget to take Nalapres
Do not take a double dose to make up for the missed dose; follow your doctor's instructions.

If you stop taking Nalapres
If you have any doubts about using 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 Nalapres and contact your doctor immediately if you experience:

difficulty breathing or swallowing, possibly accompanied by swelling of the face, lips, tongue and/or throat;
swelling of the hands, feet or ankles;
severe skin itching, accompanied by localised swelling.

If any of the side effects listed below worsen, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.
Most frequently reported side effect:

sensation of dizziness (vertigo).

Other less common side effects:

headache (cephalalgia);
dry cough;
feeling of fatigue;
sudden drop in blood pressure upon changing from a lying or sitting position to standing (orthostatic hypotension).

Still less common:

diarrhoea, vomiting, feeling unwell (nausea);
dry mouth;
skin rash;
joint inflammation causing pain and swelling (gout);
sensation of pounding heartbeat (palpitations);
chest pain;
muscle cramps, weakness, numbness or tingling of limbs, arms and legs (paraesthesia), loss of strength (asthenia);
inability to achieve an erection (erectile dysfunction);
severe kidney failure;
temporary loss of consciousness (syncope).

Rarely:

swelling of the face, hands and feet, lips, tongue, throat and/or larynx (angioedema);
clinically significant laboratory test abnormalities.

Occasionally:

increased blood sugar levels (hyperglycaemia);
increased blood uric acid levels (hyperuricaemia);
increased blood potassium levels (hyperkalaemia);
decreased blood potassium levels (hypokalaemia);
increased blood nitrogen levels;
increased blood creatinine levels.

Frequently:

reduction in the substance contained in red blood cells responsible for oxygen transport in the body (haemoglobin) and in the corresponding number of red blood cells in the blood (haematocrit). Rarely:
increase in liver enzymes, increase in blood bilirubin levels.

Side effects related to hydrochlorothiazide with frequency “not known” (frequency cannot be estimated from the available data):

loss or reduced appetite (anorexia);
stomach irritation;
constipation, diarrhoea;
yellowing of the skin and whites of the eyes (jaundice), mainly due to liver disease;
inflammation of the pancreas (pancreatitis);
inflammation of the salivary glands (sialadenitis);
sensation of dizziness (vertigo);
sensation of tingling (paraesthesia);
drowsiness, postural hypotension;
yellow discoloration of vision (xanthopsia);
reduced bone marrow function (when bone marrow fails to produce an adequate number of blood cells (aplastic anaemia)); reduced platelet count (thrombocytopenia); decreased number of white blood cells (leucopenia); decrease in a certain type of white blood cells sensitive to infections (neutropenia/agranulocytosis); destruction of red blood cells (haemolytic anaemia) – increasing the likelihood of infections;
sensitivity to light (photosensitivity);
fever, weakness;
activation or worsening of symptoms of lupus (an autoimmune disease characterised by fatigue, joint pain, skin rashes, swelling, redness, weight gain or loss, etc.), lupus-like skin reactions;
toxic epidermal necrolysis (a severe skin lesion characterised by skin irritation, blistering and areas of skin detachment);
nodular skin rash (urticaria);
inflammation of blood vessels (vasculitis), which may lead to tissue death (necrosis), inflammation of skin vessels (cutaneous vasculitis);
difficulty breathing, including due to lung inflammation (pneumonitis) or presence of fluid in the lungs (pulmonary oedema);
severe allergic reaction (anaphylactic reaction), skin rash;
increased blood sugar levels (hyperglycaemia);
presence of sugar in urine (glucosuria);
increased blood uric acid levels (hyperuricaemia), gout;
electrolyte imbalances including decreased levels of sodium, potassium, magnesium and chloride (hyponatraemia, hypomagnesaemia, hypokalaemia, hypochloraemic alkalosis) in the blood;
increased blood cholesterol and triglyceride levels;
muscle spasms and muscle weakness;
restlessness, depression, sleep disturbances;
temporary blurred vision;
kidney problems (renal dysfunction);
inflammation of the kidneys (interstitial nephritis);
sudden-onset difficulty seeing distant objects (acute myopia), decreased vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma);
skin and lip cancer (non-melanoma skin cancer).

Other side effects:

Skin disease causing red spots of variable size (purpura);
Kidney failure.

Side effects related to lisinopril
Common (may affect up to 1 in 10 people):

dizziness;
headache (cephalalgia);
temporary loss of consciousness (syncope);
sudden drop in blood pressure upon changing from a lying or sitting position to standing (orthostatic hypotension);
cough;
diarrhoea, vomiting;
kidney problems (renal dysfunction).

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

tingling of limbs, arms and legs (paraesthesia);
vertigo;
altered taste;
sleep disturbances;
mood changes;
myocardial infarction or cerebrovascular disorders, such as stroke;
sensation of pounding heartbeat (palpitations);
increased heart rate (tachycardia);
Raynaud's syndrome (pain in fingers of hands and feet turning first pale, then bluish and finally red);
rhinitis (irritation or inflammation of nasal mucosa);
nausea, abdominal pain and indigestion;
increase in liver enzymes, increase in blood bilirubin levels;
skin rash, itching;
inability to achieve an erection (erectile dysfunction);
loss of strength (asthenia);
feeling of fatigue;
increased blood nitrogen levels;
increased blood creatinine levels;
increased blood potassium levels (hyperkalaemia).

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

decreased haemoglobin, decreased haematocrit;
mental confusion;
dry mouth;
swelling of the face, hands and feet, lips, tongue, throat and/or larynx (angioedema);
urticaria;
alopecia (hair loss);
psoriasis (chronic inflammatory, non-infectious and non-contagious skin disease);
increased blood urea levels (uraemia);
kidney problems (acute renal failure);
gynaecomastia (development of breasts in men);
inadequate production of a hormone that reduces the amount of urine produced by the kidneys, called “antidiuretic hormone”;
decreased blood sodium levels (hyponatraemia).

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

reduced bone marrow function (when bone marrow fails to produce an adequate number of blood cells); reduced platelet count (thrombocytopenia); decreased number of white blood cells (leucopenia); decrease in a certain type of white blood cells sensitive to infections (neutropenia, agranulocytosis); reduction or destruction of red blood cells (anaemia, haemolytic anaemia) – increasing the likelihood of infections;
lymphadenopathy;
alteration of the body's defence system (autoimmune disease);
low blood sugar levels (hypoglycaemia);
bronchospasm (narrowing of the bronchi causing severe breathing difficulty due to reduced airflow);
sinusitis;
breathing difficulty caused by an allergic reaction including allergic alveolitis/eosinophilic pneumonia;
inflammation of the pancreas (pancreatitis);
intestinal angioedema (swelling of intestinal walls which may cause severe abdominal pain, vomiting and diarrhoea);
inflammation of the liver or bile ducts (hepatocellular and cholestatic hepatitis), liver failure;
yellowing of the skin and whites of the eyes (jaundice);
abnormal sweating (diaphoresis);
severe skin disorders including pemphigus (a blistering skin disease), toxic epidermal necrolysis and Stevens-Johnson syndrome (severe skin lesions characterised by erythema, blistering and areas of skin detachment) and erythema multiforme (a condition characterised by red spots on the skin with "target-like" appearance associated with itching), cutaneous pseudolymphoma*;
reduced or absent urination (oliguria/anuria).

Frequency not known (cannot be estimated from the available data):

depressive symptoms;
hot flushes.

* A complex disorder has been reported, including one or more of the following symptoms:

fever;
inflammation of blood vessels;
muscle pain (myalgia);
joint pain or inflammation (arthralgia/arthritis);
positive test for antinuclear antibodies;
elevated erythrocyte sedimentation rate;
elevated blood eosinophil and leucocyte concentrations;
skin rash;
sensitivity to light (photosensitivity);
other dermatological manifestations.

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. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Nalapres

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 word "Exp".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Nalapres contains

The active substances are lisinopril dihydrate and hydrochlorothiazide. Each 20 mg + 12.5 mg tablet of Nalapres contains 21.8 mg of lisinopril dihydrate (equivalent to 20 mg of anhydrous lisinopril) and 12.5 mg of hydrochlorothiazide.
The other components are: mannitol, calcium hydrogen phosphate, yellow iron oxide, maize starch, pregelatinized starch, magnesium stearate.

Description of the appearance of Nalapres and package contents
Nalapres 20 mg + 12.5 mg is available in packs of 14 yellow, hexagonal tablets,
marked “140” on one side and smooth on the other. The tablets are contained in PVC/aluminum blisters.
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, Rozzano (Milan), Italy
Vamfarma S.r.l.
Via Kennedy, 5
Comazzo (Lodi), Italy