Lisinoratio 20

Package leaflet: Information for the patient

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
Lisinoratio 20 (LISINOPRIL-TEVA 20 mg)
20 mg, tablets
Lisinoprilum
Lisinoratio 20 and LISINOPRIL-TEVA 20 mg are different brand names of the same medicinal product.
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet so that you can read it again if necessary.
• Consult your doctor or pharmacist if you have any doubts.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Lisinoratio 20 is and what it is used for
2. Important information before taking Lisinoratio 20
3. How to take Lisinoratio 20
4. Possible side effects
5. How to store Lisinoratio 20
6. Contents of the pack and other information

1. What Lisinoratio 20 is and what it is used for

Lisinopril, the active substance in Lisinoratio 20, belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (or ACE inhibitors, from the English name of the angiotensin-converting enzyme). ACE inhibitors work by reducing the tension in blood vessels, thereby lowering arterial blood pressure. The medicine acts protectively on the heart and blood vessels.
Lisinoratio 20 is used for:

• treatment of essential and renovascular hypertension as monotherapy (as a single medicine) or in combination with other antihypertensive medicines,
• treatment of heart failure as monotherapy or in combination with diuretics and, in certain cases, with digitalis preparations,
• treatment of hemodynamically stable patients in the early (24 h) phase after myocardial infarction to prevent the development of left ventricular dysfunction and heart failure,
• treatment of patients with hypertension and type 2 diabetes and early nephropathy.

2. Important information before using Lisinoratio 20

When not to use Lisinoratio 20:

• if the patient is allergic to lisinopril, any of the other ingredients of this medicine (listed in section 6), or to any other medicine in the class of angiotensin-converting enzyme (ACE) inhibitors,
• if the patient has ever experienced a condition called angioedema (rapid swelling of the skin and mucous membranes) caused by previous treatment with an angiotensin-converting enzyme inhibitor,
• in case of congenital or idiopathic (spontaneous) angioedema,
• after the 3rd month of pregnancy (Lisinoratio 20 should also be avoided in early pregnancy – see section “Pregnancy”),
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren,
• if the patient is taking or has taken a combination medicine containing sacubitril and valsartan (used in the treatment of chronic (long-term) heart failure in adults), as this increases the risk of angioedema (rapid swelling of subcutaneous tissue, e.g. in the throat area).

Warnings and precautions
Before starting treatment with Lisinoratio 20, discuss the following with your doctor, pharmacist, or nurse:

• if the patient is taking any of the following medicines, as the risk of angioedema may increase:
• racecadotril, a medicine used to treat diarrhoea,
• medicines used to prevent organ transplant rejection and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus),
• vildagliptin, a medicine used to treat diabetes,
• when using diuretics or a low-salt diet,
• if the patient has gastrointestinal disorders (diarrhoea and vomiting),
• if the patient has ever had an allergic reaction while taking other medicines in the class of angiotensin-converting enzyme inhibitors, including swelling of the face, lips, tongue and (or) throat, with difficulty breathing or swallowing,
• in patients undergoing desensitization therapy against stinging insect venom,
• if the patient has ischaemic heart disease or narrowing of arteries supplying the brain,
• in case of heart failure,
• in case of kidney or liver function disorders,
• in case of bilateral renal artery stenosis or stenosis of the artery supplying blood to the single kidney,
• if the patient taking ACE inhibitors undergoes dialysis (some types of dialysis membranes may be unsuitable),
• if the patient has vascular collagenosis,
• in case of aortic or mitral valve stenosis or increased thickness of the heart muscle (hypertrophic cardiomyopathy),
• if the patient is in the early phase after a heart attack,
• if the patient has high cholesterol levels and is undergoing a procedure called “LDL apheresis”,
• during surgical procedures under general anaesthesia,
• in case of diabetes,
• when using lithium,
• if the patient is of Black race, as lisinopril may be less effective in individuals of this race. Also, in Black patients, the adverse reaction called “angioedema” (a severe allergic reaction) may occur more frequently.
• in case of suspected or planned pregnancy. Lisinoratio 20 is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child – see section “Pregnancy and breastfeeding”,
• if the patient is taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (AIIRA), also known as a sartan – for example, valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes,
• aliskiren.

Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood levels of electrolytes (e.g. potassium).
See also the section “When not to use Lisinoratio 20”.
Lisinoratio 20 and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
In particular, inform your doctor if you are taking:

• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole – used in bacterial infections; cyclosporine – an immunosuppressive medicine used to prevent organ transplant rejection; and heparin – a medicine used to thin the blood to prevent clots),
• other medicines used to treat high blood pressure,
• diuretics,
• non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid at doses exceeding 3 g per day,
• lithium salts,
• medicines commonly used to prevent organ transplant rejection and in cancer treatment (sirolimus, everolimus, and other medicines belonging to the class of so-called mTOR inhibitors); see section “Warnings and precautions”,
• medicines that suppress the immune system (immunosuppressants, such as cytotoxic medicines, systemic corticosteroids),
• agents used in general anaesthesia,
• tricyclic antidepressants, antipsychotics, or anaesthetics,
• medicines stimulating the sympathetic nervous system (sympathomimetics),
• antidiabetic medicines,
• gold-containing medicines, such as sodium aurothiomalate, administered by injection,
• racecadotril (an antidiarrhoeal medicine),
• vildagliptin (an antidiabetic medicine).

Your doctor may recommend adjusting the dose and/or taking additional precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections “When not to use Lisinoratio 20” and “Warnings and precautions”).

Lisinoratio 20 with food and drink
Lisinoratio 20 may be taken with food and drink.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.
Pregnancy
Inform your doctor if you suspect or are planning pregnancy. Your doctor will usually advise stopping Lisinoratio 20 before a planned pregnancy or immediately after pregnancy is confirmed, and will recommend an alternative medicine. Lisinoratio 20 is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
Inform your doctor if you are breastfeeding or intend to breastfeed. Lisinoratio 20 is not recommended during breastfeeding, especially when breastfeeding a newborn or premature infant. Your doctor may recommend using another medicine.
Driving and operating machinery
Treatment with Lisinoratio 20 may cause dizziness or fatigue.

3. How to use Lisinoratio 20

This medicine should always be used as directed by a physician. If in doubt, consult a doctor or pharmacist.
Lisinoratio 5 (5 mg), Lisinoratio 10 (10 mg), and Lisinoratio 20 (20 mg) are available on the market.
Since food does not affect the absorption of lisinopril from tablets, the medicine may be taken regardless of meals.
Lisinopril should be administered once daily, at the same time each day.

Essential hypertension in patients not taking diuretics
The recommended initial dose for patients with essential hypertension is 10 mg. The usual effective maintenance dose ranges from 20 mg to 40 mg once daily at the same time each day.
The maintenance dose should be adjusted according to blood pressure values measured just before the next dose is due. The blood pressure-lowering effect may diminish as the time for the next dose approaches, regardless of the dose size, although this is most commonly observed with the 10 mg dose. In some patients, the desired reduction in blood pressure occurs after two to four weeks of maintenance therapy.
The maximum dose used in long-term controlled clinical trials was 80 mg per day; however, its use did not result in increased therapeutic efficacy.
Treatment should be initiated with a lower dose in patients:

• with renal impairment (see table: Dosing in renal impairment),
• who cannot discontinue diuretic therapy,
• with fluid and electrolyte imbalances, regardless of the cause. Prior to initiating treatment, fluid deficits should be corrected and serum electrolyte imbalances should be normalized,
• with renovascular hypertension.

Essential hypertension in patients taking diuretics
Symptomatic hypotension may occur at the start of lisinopril therapy, particularly in patients taking diuretics. Lisinoratio 20 should therefore be used cautiously, as there is an increased risk of fluid and electrolyte imbalances or renal dysfunction. Diuretic therapy should be discontinued 2–3 days before starting lisinopril.
If monotherapy with lisinopril is ineffective, diuretic therapy may be restarted (most commonly hydrochlorothiazide at a single daily dose of up to 12.5 mg). In hypertensive patients who cannot discontinue diuretic therapy prior to starting lisinopril, treatment with lisinopril should begin under close medical supervision with a reduced initial daily dose of 5 mg. In such cases, blood pressure should be monitored until the expected reduction is achieved and for an additional hour. The maintenance dose should be adjusted based on blood pressure values.

Renovascular hypertension
In some patients with renovascular hypertension, especially those with bilateral renal artery stenosis or stenosis of the artery supplying the only functioning kidney, excessive reduction in blood pressure may occur after administration of lisinopril. Renal function disturbances or even renal failure may occur. Therefore, a lower initial dose of 2.5 mg or 5 mg is recommended. The daily dose may then be gradually increased, adjusted to blood pressure values.

Hypertension in children aged 6 to 16 years
The recommended initial dose is 2.5 mg once daily for patients with body weight from 20 to 50 kg, and 5 mg once daily for patients with body weight ≥50 kg. The dose should be individually adjusted up to a maximum of 20 mg daily for patients weighing 20–50 kg and 40 mg daily for patients weighing ≥50 kg. In clinical studies involving children and adolescents, doses exceeding 0.61 mg/kg or 40 mg were not administered.
In children with reduced renal function, consideration should be given to reducing the initial dose or prolonging the interval between doses.

Heart failure
In patients with heart failure, the initial daily dose administered in the morning is 2.5 mg. Maintenance doses usually range from 5 mg to 20 mg once daily. In clinical studies, doses were increased every 4 weeks in patients requiring stronger therapy. Dose increases of lisinopril should not exceed 10 mg at a time. The dose should be adjusted according to the therapeutic response, assessed by the severity of heart failure symptoms. Lisinopril may be used in combination with diuretics and digitalis preparations.
In patients at increased risk of symptomatic hypotension, e.g., those with hyponatremia, hypovolemia, or receiving high doses of diuretics, imbalances should be corrected prior to initiating lisinopril therapy, and if possible, the diuretic dose should be reduced. The effect of the first dose of lisinopril on blood pressure should be monitored. In patients with low systolic blood pressure (<100 mmHg), the initial dose should be administered under strict medical supervision. The greatest reduction in blood pressure occurs approximately 6–8 hours after the initial dose. Monitoring of cardiovascular function, particularly blood pressure, should continue until blood pressure values stabilize.

Dose adjustment in patients with heart failure, renal dysfunction, or hyponatremia
In patients with heart failure, hyponatremia (serum sodium concentration <130 mEq/L), or moderate to severe renal impairment (creatinine clearance <30 mL/min or serum creatinine >3 mg/dL), low initial doses of 2.5 mg daily should be used under strict medical supervision.

Early phase of myocardial infarction
In hemodynamically stable patients, treatment with lisinopril should be initiated within 24 hours of the onset of myocardial infarction. The first single daily dose of lisinopril is 5 mg administered orally. After 24 hours from the first dose, 5 mg should be given, and after 48 hours, 10 mg. Subsequently, lisinopril should be continued at a dose of 10 mg once daily for 6 weeks. In combination with lisinopril, medications commonly used in myocardial infarction should be administered (if not contraindicated in the individual patient): anticoagulants, antiplatelet agents, and beta-blockers. Patients with low systolic blood pressure (≤120 mmHg) should initially receive a lower daily dose of lisinopril of 2.5 mg during the first days or for the first 3 days after myocardial infarction.
If hypotension (systolic blood pressure ≤100 mmHg) occurs during the 6-week treatment period with lisinopril, the maintenance dose should be reduced to 5 mg or 2.5 mg daily.
If prolonged and severe hypotension occurs (systolic blood pressure <90 mmHg lasting longer than 1 hour), Lisinoratio 20 should be discontinued.
Maintenance therapy lasts for 6 weeks. In patients who develop symptoms of heart failure, treatment with Lisinoratio 20 should be continued using the dosing regimen appropriate for heart failure. Lisinoratio 20 may be used in combination with intravenous or transdermal nitroglycerin.

Dose adjustment in patients with acute myocardial infarction and renal dysfunction
In patients with acute myocardial infarction and renal dysfunction (serum creatinine concentration >2 mg/dL), treatment with lisinopril should be initiated with great caution.
Dosing guidelines for lisinopril have not been established in patients with acute myocardial infarction and concomitant severe renal failure.

Diabetic nephropathy
In patients with hypertension, type 2 (insulin-independent) diabetes, and early nephropathy, the initial dose is 10 mg once daily, which may be increased to 20 mg daily if necessary, aiming to achieve a seated diastolic blood pressure <90 mmHg. In patients with renal dysfunction (creatinine clearance <80 mL/min), the initial dose of Lisinoratio 20 should be adjusted according to creatinine clearance (see Table 1).

Dosing in patients with renal impairment
Since lisinopril is excreted in urine, the daily dose should be adjusted according to creatinine clearance in patients with renal impairment (see table below). The maintenance dose and/or the interval between doses should be adjusted based on blood pressure values.

Table 1. Dose adjustment in patients with impaired renal function

* See section: "Warnings and precautions".
The maximum daily maintenance dose of lisinopril in patients with renal impairment is 40 mg.
Lisinopril is removed from plasma during hemodialysis. Patients undergoing dialysis should receive the appropriate daily dose of lisinopril after the dialysis session.

Dosage in elderly patients
The pharmacological effect of lisinopril administered at the same doses in elderly and younger patients is very similar; however, it has been shown that maximum serum concentrations of lisinopril in elderly patients are approximately twice as high as in younger patients. Doses of lisinopril in elderly patients should be increased very cautiously.

Dosage in children
Experience regarding the efficacy and safety of lisinopril in the treatment of hypertension in children above 6 years of age is limited. There is no experience with the use of lisinopril in indications other than hypertension. The use of lisinopril in children for indications other than hypertension is not recommended.
The use of lisinopril is not recommended in children under 6 years of age or in children with severe renal impairment (GFR < 30 ml/min/1.73 m²).

Use of a higher than recommended dose of Lisinoratio 20
If an overdose is taken, contact a doctor or pharmacist, or go to a hospital immediately. Symptoms that may occur include: hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, bradycardia, palpitations, dizziness, anxiety, and cough.

Missed dose of Lisinoratio 20
Do not take a double dose to make up for a missed dose.

Discontinuation of Lisinoratio 20
If in doubt about using the medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects have been reported during treatment with Lisinoratio 20 and other angiotensin inhibitors, with the following frequencies:

Common (occur in 1 to 10 out of 100 patients)

• headache;
• dizziness or lightheadedness, especially when standing up quickly;
• cough;
• diarrhoea;
• vomiting;
• kidney-related disorders.

Uncommon (occur in 1 to 10 out of 1,000 patients)

• mood changes;
• changes in skin colour of fingers or toes (bluish discoloration followed by redness), or numbness or tingling in fingers;
• taste disturbances;
• sleep disorders;
• drowsiness;
• peripheral dizziness;
• difficulty falling asleep;
• stroke;
• palpitations, rapid heartbeat;
• Raynaud's syndrome;
• nasal mucosal inflammation;
• nausea, stomach pain or indigestion;
• skin rash or itching;
• impotence;
• fatigue or weakness;
• significant drop in blood pressure may occur in patients with the following conditions: ischaemic heart disease; aortic stenosis (narrowing of the artery carrying blood from the heart), renal artery stenosis, or heart valve stenosis; hypertrophy of the heart muscle. In case of hypotension, patients may experience dizziness or lightheadedness, especially when standing up quickly;
• changes in blood test results assessing liver and kidney function;
• myocardial infarction.

Rare (occur in 1 to 10 out of 10,000 patients)

• feeling of disorientation (confusion);
• syndrome of inappropriate antidiuretic hormone secretion (SIADH);
• dryness of the oral mucosa;
• hypersensitivity and/or angioedema: angioedema of the face, limbs, lips, tongue, glottis and/or larynx;
• urticaria;
• hair loss;
• psoriasis (skin disease);
• smell disturbances;
• gynaecomastia (breast enlargement in males);
• decreased haemoglobin concentration, decreased haematocrit;
• increased serum bilirubin concentration, hyponatraemia (low blood sodium);
• uraemia, acute renal failure.

Very rare (occur in less than 1 out of 10,000 patients)

• bone marrow suppression, anaemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, haemolytic anaemia, lymphadenopathy, autoimmune disease;
• bronchospasm, sinusitis, allergic alveolitis/eosinophilic pneumonia;
• low blood glucose (hypoglycaemia);
• pneumonia. Symptoms include: cough, shortness of breath and high temperature (fever);
• yellowing of the skin or whites of the eyes (jaundice);
• pancreatitis;
• intestinal angioedema;
• hepatitis – parenchymal or cholestatic, jaundice;
• liver failure;
• increased sweating;
• bullous eruption;
• toxic epidermal necrolysis;
• Stevens-Johnson syndrome;
• erythema multiforme;
• cutaneous pseudolymphoma;
• decreased urine output or anuria.

Unknown frequency (cannot be estimated from available data)

• symptoms of depression;
• fainting.

The following symptoms have also been reported: anorexia, constipation, bloating, and a syndrome involving one or more of the following symptoms occurring alone or together: fever, vasculitis, muscle pain, joint pain and/or arthritis, positive antinuclear antibody (ANA) titre, increased ESR, eosinophilia and leukocytosis, rash, photosensitivity, and other skin symptoms.
Safety data from clinical trials indicate that lisinopril is generally well tolerated in the treatment of hypertension in children and adolescents. The safety profile in this patient group is comparable to that in adults.
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, consult a doctor or pharmacist.
Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309; website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to provide more information on the safe use of this medicine.

5. How to store Lisinoratio 20

Keep this medicine out of sight and reach of children.
Do not store above 25°C. Store in the original packaging.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Translation of some information on the immediate packaging:
Ch.-B./Verwendbar bis siehe Aufdruck – Batch number and expiry date see imprint
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Lisinoratio 20 contains

• The active substance is lisinopril (in the form of lisinopril dihydrate).
• Other components of the medicine are: mannitol, calcium hydrogen phosphate dihydrate, corn starch, magnesium stearate, and pregelatinized corn starch.

What Lisinoratio 20 looks like and contents of the pack
White, oval tablet with the imprint “LSN 20” on one side and a central break line on the other side.
Packaging: 30 tablets.
For more detailed information, please contact the responsible party or the parallel importer.
Marketing Authorisation Holder in Germany, the country of export:
TEVA GmbH
Graf-Arco-Str. 3
89079 Ulm, Germany
Manufacturer:
Pharmachemie B.V.
Swensweg 5, Postbus 552
2003 RN Haarlem
The Netherlands
TEVA Pharmaceutical Works Private Limited Company
Pallagi út 13
H-4042 Debrecen, Hungary
Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing Authorisation Number in Germany, the country of export: 57016.03.00
Parallel Import Authorisation Number: 83/23