Lisinoratio 5

Package leaflet: Information for the patient

Lisinoratio 5, 5 mg, tablets
Lisinoratio 10, 10 mg, tablets
Lisinoratio 20, 20 mg, tablets
Lisinoprilum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

DO NOT USE IN PREGNANT WOMEN
Contents of the leaflet

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

1. What Lisinoratio is and what it is used for

Lisinoratio contains lisinopril (an angiotensin-converting enzyme [ACE] inhibitor), which inhibits the activity of the enzyme that converts angiotensin I into angiotensin II, a substance that causes vasoconstriction and increases blood pressure.
Inhibition of angiotensin-converting enzyme leads to reduced plasma concentration of angiotensin II, decreased aldosterone secretion, lowering of blood pressure in patients with hypertension, and reduction of symptoms of heart failure. After oral administration, lisinopril is absorbed by approximately 25%; food does not affect drug absorption. Maximum serum concentration is reached after 6–8 hours. The elimination half-life of the drug is approximately 12 hours. Long-term administration of therapeutic doses of Lisinoratio does not lead to drug accumulation in plasma. The drug is not metabolized in the body and is excreted unchanged in urine.

Lisinoratio is indicated for:

• Treatment of essential and renovascular hypertension as monotherapy (as a single agent) or in combination with other antihypertensive drugs
• Treatment of heart failure as monotherapy or in combination with diuretics and, in selected cases, with digitalis preparations
• Treatment of hemodynamically stable patients in the early (within 24 hours) phase following acute myocardial infarction, to prevent the development of left ventricular dysfunction and heart failure
• Treatment of patients with hypertension and type 2 diabetes mellitus and associated renal complications with microalbuminuria

2. Important information before using Lisinoratio

When not to use Lisinoratio:

• if the patient is allergic to lisinopril or any of the other ingredients of this medicine
  (listed in section 6),
• if the patient has ever experienced a condition called angioedema due to previous treatment with an angiotensin-converting enzyme (ACE) inhibitor, characterized by swelling of the face, lips, tongue and (or) throat, difficulty swallowing, or breathing (feeling of breathlessness);
• in case of hereditary or idiopathic (spontaneous) angioedema,
• in pregnant or breastfeeding women;
• if the patient has diabetes or kidney function impairment and is being treated with a blood pressure-lowering medicine containing aliskiren,
• if the patient is taking a medicine containing a neprilysin inhibitor (e.g. sacubitril). Lisinoratio must not be used within 36 hours before or after treatment with sacubitril + valsartan, which contains a neprilysin inhibitor.

Warnings and precautions
Before starting Lisinoratio, discuss this with your doctor or pharmacist.
Lisinoratio should be taken at the doses prescribed by the doctor throughout the treatment period, even if this period is very long.
Do not change the dose or the way of taking the medicine on your own, without doctor's advice, especially in case of increased risk of kidney function disorders or in patients with heart failure.
Inform your doctor 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 function disorders related to diabetes,
• aliskiren.

The doctor may recommend regular monitoring of kidney function, blood pressure, and serum electrolyte levels (e.g. potassium).
See also the section "When not to use Lisinoratio".
Inform your doctor about all other medicines you are currently taking or have recently taken, including those available without a prescription. Inform your doctor about the use of antidiabetic medicines – oral or insulin, lithium salts (used, among others, in the treatment of depression), gold salts (used in the treatment of a specific type of joint pain or inflammation).
Due to the increased risk of hypotension, which may manifest as dizziness, vision disturbances, or fainting, inform your doctor before starting Lisinoratio if you are taking diuretics.
Also inform your doctor about any symptoms or disorders, particularly those affecting the kidneys, vomiting and diarrhoea, dialysis treatment, salt-free diet, or other medicines that may increase serum potassium levels (e.g. medicines containing trimethoprim).
Inform your doctor about any previous hypersensitivity (allergic) reactions, especially if they were associated with swelling of the face, lips, tongue and (or) throat, difficulty breathing or swallowing.
If hypotension occurs, manifesting as, for example, vision disturbances, dizziness, or fainting, lie down with your legs raised. If symptoms do not subside after several minutes, contact your doctor.
Exercise caution when using potassium-containing preparations (including dietary supplements) and potassium-sparing diuretics during Lisinoratio therapy.
In patients with ischemic heart disease or significant narrowing of arteries supplying the brain, excessive lowering of blood pressure may lead to myocardial infarction or cerebral ischemia.
While taking Lisinoratio or another ACE inhibitor, angioedema may occur [swelling of the face, extremities, lips, tongue, larynx and (or) throat]. In such a case, discontinue the medicine immediately and consult your doctor.
In patients taking ACE inhibitors and undergoing dialysis with high-flux dialysis membranes, a pseudoallergic reaction may occur. Inform your doctor about lisinopril use before dialysis. Similar reactions have been observed during low-density lipoprotein apheresis using dextran sulfate. This method should not be used in patients taking ACE inhibitors.
In patients taking lisinopril and undergoing desensitization to insect venom (Hymenoptera), a life-threatening pseudoallergic reaction may occur. Your doctor may recommend discontinuing the medicine during desensitization or avoiding the desensitization procedure.
Inform your doctor about taking Lisinoratio before general anaesthesia for surgical procedures.
At the beginning of treatment with Lisinoratio, excessive lowering of blood pressure may occur, which may subside during continued treatment, and may manifest as excessive fatigue and dizziness. If such symptoms occur, lie down with your legs raised; if symptoms do not subside after several minutes, contact your doctor.
To assess treatment efficacy and determine the lowest effective dose, your doctor may recommend frequent blood pressure measurements, especially at the beginning of treatment and after dose adjustments.
Your doctor may recommend frequent monitoring of serum electrolyte levels, especially in patients at increased risk of kidney failure or those taking potassium-sparing diuretics.
If symptoms such as fever, swollen lymph nodes, tonsillitis, nosebleeds, gum bleeding, or excessive tendency to develop skin petechiae occur, contact your doctor immediately, as they may be related to excessive reduction in white blood cell or platelet count.
Inform your doctor if you are taking a medicine containing a neprilysin inhibitor (e.g. sacubitril).
Inform your doctor if you are taking a medicine containing vildagliptin.

Children and adolescents
Experience regarding the efficacy and safety of lisinopril in treating hypertension in children over 6 years of age is limited. There is no experience with lisinopril use in indications other than hypertension. Lisinopril is not recommended for use in children for indications other than hypertension.
Lisinopril is not recommended for use in children under 6 years of age or in children with severe kidney function impairment.

Lisinoratio and other medicines
Generally, Lisinoratio can be taken with other medicines. However, inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use, as some medicines may affect the action of others.
Your doctor may recommend dose adjustments and/or additional precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to use Lisinoratio" and "When to exercise special caution with Lisinoratio").

For correct dose prescription of Lisinoratio, it is particularly important that the doctor knows about the use of: other blood pressure-lowering medicines, diuretics, potassium-containing preparations (including salt substitutes), or other medicines that may increase serum potassium levels (e.g. medicines containing trimethoprim), antidiabetic medicines (including oral antidiabetics or insulin), lithium (a medicine used in the treatment of certain types of depression), and certain medicines used to treat pain and joint diseases. Inform your doctor about taking an mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) or a medicine containing a neprilysin inhibitor (e.g. sacubitril) or vildagliptin (an antidiabetic medicine), as concomitant use with Lisinoratio may increase the risk of an allergic reaction called angioedema.
Concomitant use of Lisinoratio with diuretics may enhance the blood pressure-lowering effect.
Indomethacin and other non-steroidal anti-inflammatory drugs (e.g. acetylsalicylic acid) reduce the antihypertensive effect of Lisinoratio.
Concomitant administration of Lisinoratio and lithium salts may reduce lithium excretion. Your doctor will recommend regular monitoring of serum lithium levels and, if necessary, lower lithium doses.
Concomitant use of potassium supplements, potassium-containing salt substitutes, or potassium-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene) may lead to hyperkalemia (increased serum potassium levels).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Lisinoratio must not be used in pregnant women.
ACE inhibitors, including lisinopril, may cause fetal harm or death if used during the second or third trimester of pregnancy (i.e. from the fourth month of pregnancy until delivery). If pregnancy is detected during treatment, discontinue the medicine, contact your doctor, and change the treatment according to medical advice.
Women who are pregnant or planning to become pregnant should inform their doctor before starting Lisinoratio.
Women of childbearing potential taking lisinopril should use effective contraception.
Breastfeeding
It is not known whether lisinopril passes into human milk. If breastfeeding or planning to breastfeed, discuss this with your doctor.

Driving and operating machinery
Individual response to the medicine may vary. Some adverse effects reported during lisinopril use may affect the ability to drive or operate machinery (see section 4).

Lisinoratio contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to use Lisinoratio

This medicine should always be used as directed by your doctor. If in doubt, consult your doctor or pharmacist.
Since food does not affect the absorption of lisinopril from tablets, the medicine may be taken independently of meals.
Lisinopril should be administered once daily, at the same time each day.

Essential hypertension
The recommended initial dose for patients with essential hypertension is 10 mg once daily.
The usual effective maintenance dose ranges from 20 mg once daily. The maximum daily dose is 80 mg.
For patients already treated with diuretics, the physician usually recommends discontinuation or reduction of the diuretic dose 2–3 days before initiating treatment with Lisinoratio. The recommended starting dose is 5 mg.

Renovascular hypertension
In some patients with renovascular hypertension, especially those with bilateral renal artery stenosis or stenosis of the artery supplying the sole functioning kidney, the initial dose is 2.5 mg or 5 mg once daily. The physician may subsequently recommend increasing the dose.

Heart failure
For 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 daily.

In patients who cannot discontinue diuretics, or in dehydrated patients, patients with sodium deficiency, or those with renal impairment, the physician should prescribe a lower dose of lisinopril, adjusted according to the severity of renal impairment (creatinine clearance).

Acute phase of myocardial infarction
During the acute phase of myocardial infarction, in hemodynamically stable patients (in whom cardiogenic shock has not occurred), the physician should prescribe the first dose of 5 mg within 24 hours of the onset of infarction. After another 24 hours, the same dose (5 mg) should be administered, and after 48 hours from the onset of infarction, the dose should be increased to 10 mg of lisinopril. Treatment should then continue with a once-daily dose of 10 mg for 6 weeks. If there are no contraindications, the physician will also recommend concomitant use of other drugs commonly used in the treatment of myocardial infarction (anticoagulants, antiplatelet agents, and beta-blockers).

Patients with low systolic blood pressure (≤120 mmHg) should receive a lower initial dose of 2.5 mg of lisinopril daily, both at the beginning of treatment and for the following three days. If hypotension occurs (systolic blood pressure below 100 mmHg), the physician may recommend reducing the maintenance dose to 5 mg or 2.5 mg. If prolonged hypotension occurs (systolic blood pressure below 90 mmHg lasting longer than 1 hour), the physician should recommend discontinuation of Lisinoratio.

Diabetic nephropathy
In patients with hypertension and non-insulin-dependent (type 2) diabetes, the usual initial dose of Lisinoratio is 10 mg once daily. The maintenance daily dose should be adjusted to achieve the currently recommended diastolic blood pressure values in the sitting position for these patients.

Renal impairment
In patients with impaired renal function, dosage should be adjusted according to the severity of impairment based on creatinine clearance values, using the table below.

Then the doctor usually recommends gradually increasing the dose. The maximum single daily dose of lisinopril is 40 mg.

Use in children aged 6 to 16 years with arterial hypertension
The doctor will determine the dose appropriate for the child. It depends on body weight.
For children with body weight from 20 to < 50 kg, the recommended initial dose is 2.5 mg once daily.
For children with body weight ≥ 50 kg, the recommended initial dose is 5 mg once daily.

Use of a higher than recommended dose of Lisinoratio
If an excessive dose of Lisinoratio is taken, the patient should immediately consult a doctor. Medical observation is necessary. The most likely symptom of overdose is excessive lowering of arterial pressure and associated dizziness.

Missed dose of Lisinoratio
The medicine should be taken at the dose prescribed by the doctor.
If a dose is missed at the usual time, the patient should not take an extra dose. The next day, resume taking the medicine regularly at the dose recommended by the doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Lisinopril is generally well tolerated. Common adverse effects include dizziness, headache, diarrhoea, vomiting, renal dysfunction, cough, and dizziness related to sudden drop in blood pressure upon rapid standing (orthostatic symptoms).
Other adverse effects occurring not uncommonly include myocardial infarction or cerebrovascular incident, probably secondary to excessive blood pressure reduction in patients at high risk, sensation of rapid heartbeat (palpitations), fast heartbeat (tachycardia), reduced blood flow to fingers and toes, manifesting as colour change accompanied by cold sensation or numbness (Raynaud's phenomenon), nasal mucosal inflammation, abdominal pain, indigestion, nausea, rash, itching, loss of strength (weakness), mood disturbances, sleep disturbances, tingling, tickling sensation, pricking sensation or burning sensation (paresthesia), impotence, fatigue, dizziness, taste disturbances, increased blood urea concentration, increased serum creatinine concentration, increased liver enzyme activity, increased blood potassium concentration (hyperkalemia).
Other adverse effects occurring rarely include decreased haemoglobin concentration, decreased number of red blood cells (decreased haematocrit), disorientation, dryness of the oral mucosa, hypersensitivity/angioedema (swelling of the face, limbs, lips, tongue, larynx and (or) pharynx), urticaria, hair loss (alopecia), elevated levels of urea, creatinine and other nitrogenous end products of protein and amino acid metabolism in blood (uraemia), acute renal failure, gynaecomastia, increased serum bilirubin concentration, low blood sodium concentration (hyponatremia).
Other adverse effects may occur very rarely and some of them may be severe.
Examples of such adverse effects include yellowing of the skin and (or) eyes (jaundice), oliguria or anuria, and severe abdominal pain. Other adverse effects occurring very rarely include: bone marrow suppression, anaemia, low platelet count (thrombocytopenia), reduced total number of white blood cells (leukopenia), low number of one type of white blood cells – neutrophils (neutropenia), marked reduction in number of one type of white blood cells – granulocytes (agranulocytosis), haemolytic anaemia, enlarged lymph nodes (lymphadenopathy), autoimmune disease, low blood sugar concentration (hypoglycaemia), narrowing of airways (bronchospasm), sinusitis, pancreatitis, intestinal wall swelling (intestinal angioedema), liver inflammation (hepatocellular or cholestatic), liver failure, excessive sweating, blistering of skin and mucous membranes (bullous eruption), blistering and peeling of the skin (toxic epidermal necrolysis), Stevens-Johnson syndrome, erythema multiforme.
The following adverse effects have also been reported, but frequency cannot be determined from available data (frequency not known): gout, decreased libido, depression, somnolence, stroke, fainting, angina pectoris, cardiac arrhythmia, shortness of breath, pulmonary infiltrates, laryngitis, bronchitis, nasal mucosal congestion, sore throat, anorexia, constipation, flatulence, photosensitivity, pseudolymphoma of the skin, urinary tract infection, chest pain, erythema, syndrome of inappropriate antidiuretic hormone secretion (SIADH), blurred vision, back pain, joint pain, muscle cramps and shoulder pain.
A syndrome comprising one or more of the following symptoms has been reported: fever, vasculitis, muscle pain, joint pain or arthritis, positive titre of antinuclear antibodies (ANA), increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or other skin symptoms.
For additional information on adverse effects, consult your doctor or pharmacist.
If any adverse effects or worrying symptoms occur, inform your doctor or pharmacist.
Discontinue Lisinoratio and seek immediate medical advice in any of the following cases:

• if swelling of the face, lips, tongue, larynx and (or) pharynx occurs, which may cause difficulty in breathing or swallowing
• if swelling of hands, ankles or feet occurs
• if urticaria occurs

A greater reduction in blood pressure may occur after the first dose of the medicine than with subsequent doses. This may manifest as fainting or dizziness. If this occurs, the patient should lie down. In case of doubt, contact your doctor.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Lisinoratio

Keep this medicine out of the sight and reach of children.
Lisinoratio 5: No special storage instructions apply.
Lisinoratio 10, Lisinoratio 20: Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Lisinoratio contains

• The active substance is lisinopril.
• Other ingredients are: mannitol, calcium hydrogen phosphate dihydrate, maize starch, sodium croscarmellose, magnesium stearate. Lisinoratio 10 mg tablets additionally contain the colouring agent PB-24823 Pink [maize starch, iron(III) oxide, iron(II,III) oxide, iron(III) hydroxide]. Lisinoratio 20 mg tablets additionally contain the colouring agent PB-24824 Pink [maize starch, iron(III) oxide, iron(II,III) oxide, iron(III) hydroxide].

What Lisinoratio looks like and contents of the pack
Lisinoratio 5: white, round, biconvex tablets, with a score line on one side.
Lisinoratio 10: light pink, round, biconvex tablets, with a score line on one side.
Lisinoratio 20: pink, round, biconvex tablets, with a score line on one side.
Packaging:
30 tablets
Marketing Authorisation Holder:
ratiopharm GmbH, Graf-Arco-Strasse 3, 89079 Ulm, Germany
Manufacturer:
Merckle GmbH,
Ludwig-Merckle-Strasse 3,
89143 Blaubeuren,
Germany
Teva Operations Poland Sp. z o.o.
ul. Mogilska 80
31-546 Kraków, Poland
For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.
Teva Pharmaceuticals Polska Sp. z o.o.,
tel. +48 22 345 93 00