Prinzide

Package leaflet: Information for the patient

Prinzide 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 adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Prinzide is and what it is used for

Prinzide 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 a greater amount of urine, thereby reducing
blood volume.
Prinzide is used for the treatment of high blood pressure (essential hypertension) in
patients in whom lisinopril alone is not sufficient to adequately control it.

2. What you need to know before taking Prinzide

Do not take Prinzide if:

• you are allergic to the active substances lisinopril or hydrochlorothiazide, or to any of the other components 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 the face, lips, tongue and/or throat, leading to difficulty 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 (Prinzide should also be avoided in early 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 have severe kidney problems (creatinine clearance < 30 ml/min);
• you have 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, for example in the throat).

Warnings and precautions
Talk to your doctor or pharmacist before taking Prinzide 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), following a low-salt diet, or after vomiting or diarrhoea. A drop in blood pressure may also occur if you have renin-dependent high blood pressure;
• you have low blood pressure (hypotension), which may cause weakness or dizziness. A significant drop in blood pressure can be dangerous, especially for patients with impaired blood flow to the heart (ischaemic heart disease) or brain (ischaemic cerebrovascular disease);
• 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 severe heart problems and your kidney function depends on the renin-angiotensin-aldosterone system; treatment with ACE inhibitors may be associated with reduced urine output (oliguria), increasing levels of nitrogen in the blood, and rarely, severe kidney problems and/or death. Your doctor will exercise caution when prescribing ACE inhibitor therapy;
• you have liver problems or suffer from a disease that could lead to destruction of liver cells (progressive hepatopathy);
• you are scheduled for surgery requiring anaesthesia;
• 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 may advise you to stop taking hydrochlorothiazide before the test;
• you suffer from gout, an inflammatory joint condition causing pain and swelling;
• you have 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 require blood separation treatment (apheresis), for example for high cholesterol levels. Your doctor may temporarily stop Prinzide treatment to prevent possible allergic reactions;
• you are undergoing or planning to undergo treatment to reduce the effects of an allergy, for example following an insect sting (desensitisation therapy). If you are

taking Prinzide during this treatment, you may experience a severe allergic reaction;

• you develop a persistent dry cough for a prolonged period after starting Prinzide treatment. Discuss this with your doctor;
• you experience changes in blood cell counts (white blood cells, red blood cells, platelets) or a significant drop in a specific type of infection-fighting white blood cells (agranulocytosis), especially if you have connective tissue disease (collagenosis) involving blood vessels or are taking immunosuppressive medicines;
• you have narrowing (stenosis) of the aortic or mitral valve, or thickening of the heart walls (hypertrophic cardiomyopathy);
• you are pregnant (or suspect or are planning pregnancy) or breastfeeding (see section “Pregnancy and breastfeeding”);
• if you are of African origin, you may be more likely to develop angioedema (characterised by swelling of the face, lips, tongue, throat, or sudden breathing difficulties);
• you experience vision changes or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure, which may occur from a few hours to weeks after taking Prinzide. 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 and lip cancers. Protect your skin from sun and UV exposure while taking Prinzide;
• 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 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.
• you have previously experienced respiratory or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking Prinzide, consult a doctor immediately.

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

Stop taking Prinzide and inform your doctor immediately if you experience:

• difficulty breathing, possibly accompanied by swelling of the face, lips, tongue and/or throat;
• swelling of the face, lips, tongue and/or throat, which may also cause difficulty swallowing;
• swelling of the hands, feet or ankles;
• severe skin itching accompanied by localized swelling.

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

Elderly
In clinical studies, the efficacy and tolerability of combined lisinopril and hydrochlorothiazide were found to be similar in elderly and younger hypertensive patients.

Other medicines and Prinzide
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Do not take Prinzide with sacubitril/valsartan (a medicine for heart failure) due to increased risk of angioedema (rapid swelling under the skin, for example in the throat). See section “Do not take Prinzide”.
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 (e.g. trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; heparin, a medicine used to thin the blood and prevent clots);
• 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 may cause 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 increase urine elimination (diuretics);
• lithium, used to treat bipolar disorder;
• indomethacin, 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, which may increase calcium levels in the blood;
• injectable gold (used to treat rheumatoid arthritis, a chronic joint inflammation);
• sympathomimetics (medicines acting mainly on the sympathetic nervous system, which controls internal organs, especially blood circulation and the heart);
• allopurinol, used to treat gout;
• 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), for treating fungal infections;
• corticosteroids, such as cortisone, beclometasone, used, for example, for inflammation or asthma;
• carbenoxolone, for treating gastrointestinal ulcers;
• adrenocorticotropic hormone, which acts by stimulating the adrenal glands;
• medicines for high cholesterol, such as cholestyramine and colestipol;
• sotalol (a medicine for heart rhythm disorders, antiarrhythmics);
• adrenaline or noradrenaline, known as pressor amines;
• an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections “Do not take Prinzide” and “Warnings and precautions”). Your doctor may need to adjust your dose and/or take additional precautions.

Prinzide with food, drinks and alcohol
Prinzide should not be taken with alcohol, as this may increase the blood pressure-lowering effects of Prinzide.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Prinzide is not recommended during the first three months of pregnancy. Do not take Prinzide if you are more than three months pregnant, as it may cause serious harm to the unborn baby if used beyond the third month of pregnancy. If you think you may be pregnant or are planning a pregnancy, inform your doctor, who may advise stopping Prinzide and prescribe an alternative treatment.
Prinzide is not recommended during breastfeeding. Inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor may prescribe an alternative treatment during breastfeeding, especially if your baby is a newborn or premature.

Driving and using machines
Prinzide may reduce your ability to drive or operate machinery. This is more likely at the beginning of treatment, after dose adjustments, or when taken with alcohol. These effects depend on your individual sensitivity. If you are affected, do not drive or operate machinery.
Dizziness or fatigue may occur during treatment with Prinzide.

For athletes
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Prinzide

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 dose.
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 Prinzide, in order to avoid excessive lowering of blood pressure during the initial phase of treatment.

Use in children and adolescents
The use of Prinzide 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 impairment
Your doctor may consider adjusting the dose.

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

Treatment in case of overdose with Prinzide
In case of overdose with Prinzide, your doctor will discontinue treatment with Prinzide and administer physiological saline solution via intravenous injection to increase blood volume and prevent excessive lowering of blood pressure. You will be rehydrated to compensate for fluid loss, and mineral salts will be administered to correct electrolyte imbalances in your body fluids.
If you have recently ingested an excessive dose of Prinzide, you will receive treatments in hospital to remove the medicine from your body: induction of vomiting, gastric lavage, blood purification (hemodialysis).

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

If you stop taking Prinzide
If you have any questions about the use of 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 Prinzide and contact your doctor immediately if you experience:

• difficulty breathing, even accompanied by swelling of the face, lips, tongue and/or throat;
• swelling of the face, lips, tongue and/or throat, which may also cause difficulty swallowing;
• 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:

• dizziness.

Other less frequent 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).

Even less common:

• diarrhoea, vomiting, feeling of discomfort (nausea);
• dry mouth;
• skin rash;
• joint inflammation causing pain and swelling (gout);
• sensation of heart pounding (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;
• transient loss of consciousness (syncope).

Rarely:

• swelling of the face, hands and feet, lips, tongue, throat and/or larynx (angioedema);
• clinically significant changes in laboratory parameters.

Occasionally:

• increase in blood sugar levels (hyperglycaemia);
• increase in blood uric acid levels (hyperuricaemia);
• increase in blood potassium levels (hyperkalaemia);
• decrease in blood potassium levels (hypokalaemia);
• increase in blood nitrogen levels;
• increase in blood creatinine levels.

Frequently:

• decrease 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.

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;
• sensation of tingling (paraesthesia);
• drowsiness, postural hypotension;
• yellow discoloration of vision (xanthopsia);
• reduced bone marrow function (when the bone marrow fails to produce a sufficient 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 lupus symptoms (an immune system disease presenting with 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);
• pustular, vesicular and bullous skin rash (exanthema);
• difficulty breathing, even due to lung inflammation (pneumonitis) or presence of fluid in the lungs (pulmonary oedema);
• severe allergic reaction (anaphylactic reaction), skin rash;
• increase in blood sugar levels (hyperglycaemia);
• presence of sugar in urine (glucosuria);
• increase in 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;
• increase in blood cholesterol and triglyceride levels;
• muscle spasms and muscle weakness;
• agitation, depression, sleep disturbances;
• temporary blurred vision;
• kidney problems (renal dysfunction);
• inflammation of the kidneys (interstitial nephritis);
• sudden onset of reduced distance vision (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);
• cancer of the skin and lips (non-melanoma skin cancer).

Other side effects:

• Skin disease causing red spots of variable size (purpura);
• Kidney failure;
• In very rare cases, Stevens-Johnson syndrome may occur, a skin disease characterised by blistering, redness and peeling.

In isolated cases:

• increase in blood calcium levels (hypercalcaemia).

Possible:

• changes in heart rhythm (cardiac arrhythmias).

Very rare frequency:

• acute respiratory distress (signs include severe shortness of breath, fever, weakness and confusion).

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

• dizziness;
• headache (cephalalgia);
• transient 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 diseases, e.g. stroke;
• sensation of heart pounding (palpitations);
• increased heart rate (tachycardia);
• Raynaud's syndrome (pain in fingers of hands and feet turning first pale, then bluish, and finally reddish);
• 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;
• increase in blood nitrogen levels;
• increase in blood creatinine levels;
• increase in blood potassium levels (hyperkalaemia).

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

• decrease in haemoglobin, decrease in 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);
• increase in 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";
• decrease in blood sodium levels (hyponatraemia).

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

• reduced bone marrow function (when the bone marrow fails to produce a sufficient 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 with 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 compared to normal (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 eosinophil and leucocyte counts in the blood;
• 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 Prinzide

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 any medicine 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 Prinzide contains

• The active substances are lisinopril dihydrate and hydrochlorothiazide. Each 20 mg + 12.5 mg tablet of Prinzide 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 phosphate dibasic, yellow iron oxide, maize starch, pregelatinized starch, magnesium stearate.

Description of the appearance of Prinzide and contents of the pack
Prinzide 20 mg + 12.5 mg is available in packs containing 14 yellow, hexagonal tablets,
imprinted with '140' on one side and smooth on the other. The tablets are contained in PVC and
aluminum blisters.

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

Manufacturers
Doppel Farmaceutici S.r.l.
Via Volturno, 48
20089 Quinto de' Stampi, Rozzano (MI), Italy.
Vamfarma S.r.l.
Via Kennedy, 5
26833 Comazzo (Lodi), Italy.