Ranopril

Patient Information Leaflet

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

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

DO NOT USE IN PREGNANT WOMEN
Table of Contents

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

1. What Ranopril is and what it is used for

Ranopril contains lisinopril (an angiotensin-converting enzyme inhibitor, ACE inhibitor), which inhibits the activity of the enzyme that converts angiotensin I into angiotensin II, a substance that causes blood vessel constriction and increases blood pressure.
Inhibition of angiotensin-converting enzyme leads to reduced levels of angiotensin II in blood plasma, decreased aldosterone secretion, reduction in blood pressure in patients with hypertension, and alleviation of heart failure symptoms. 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 Ranopril does not lead to accumulation in plasma. The drug is not metabolized in the body and is excreted unchanged in urine.
Ranopril is indicated for:

• Treatment of essential and renovascular hypertension, either as monotherapy or in combination with antihypertensive drugs from other classes;
• Treatment of heart failure, either as monotherapy or in combination with diuretics and digitalis glycosides;
• Treatment of hemodynamically stable patients in the early phase (within 24 hours) of acute myocardial infarction, to prevent the development of left ventricular dysfunction and heart failure;
• Treatment of patients with diabetes and hypertension and coexisting renal complications with microalbuminuria.

2. Important information before using Ranopril

When not to use Ranopril:

• 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 angioedema (a type of swelling) while taking angiotensin-converting enzyme (ACE) inhibitors, manifesting as swelling of the face, lips, tongue and (or) throat, difficulty in swallowing or breathing (feeling of suffocation);
• if the patient has hereditary or idiopathic angioedema;
• in women who are pregnant or breastfeeding;
• 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 or has recently taken a combination medicine containing sacubitril and valsartan (used to treat chronic heart failure in adults), as this increases the risk of angioedema (rapid swelling of the subcutaneous tissue, e.g. in the throat area).

Warnings and precautions
Before starting treatment with Ranopril, discuss this with your doctor, pharmacist or nurse.
Ranopril should be taken at the doses prescribed by the doctor throughout the entire treatment period, even if it is very long.
Do not change the dose or method of administration on your own, without a doctor's advice, especially in cases 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 blood electrolyte levels (e.g. potassium).

Inform your doctor if the patient is taking any of the following medicines, as the risk of angioedema may increase (sudden swelling of subcutaneous tissue, e.g. in the throat area):

• mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus – medicines most commonly used to prevent rejection of transplanted organs or in cancer treatment);
• racecadotril – a medicine used to treat diarrhoea;
• vildagliptin – a medicine used to treat diabetes.

Inform your doctor about all other medicines you are currently taking or have recently taken, including those available without a prescription.
In particular, inform your doctor about taking antidiabetic medicines – oral agents 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 (low blood pressure), which may manifest as dizziness, vision disturbances or fainting, inform your doctor before starting Ranopril if you are taking diuretics.
Also inform your doctor about any symptoms or disorders, particularly those affecting the kidneys, vomiting, diarrhoea, dialysis treatment or a salt-free diet.
Inform your doctor about any history of hypersensitivity (allergic) reactions, especially if they involved swelling of the face, lips, tongue and (or) throat, or difficulty in breathing or swallowing.
While taking Ranopril or another medicine from the ACE inhibitor class, angioedema (swelling of the face, limbs, lips, tongue, larynx and (or) throat) may occur. In such a case, discontinue the medicine immediately and consult your doctor.
If hypotension occurs, manifesting as 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 treatment with Ranopril.
In patients with ischemic heart disease or significant narrowing of the arteries supplying the brain, excessive lowering of blood pressure may lead to myocardial infarction or cerebral ischemia.
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 occurred during low-density lipoprotein apheresis using dextran sulfate. This procedure 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 advise against the procedure.
Inform your doctor about taking Ranopril before undergoing general anaesthesia for surgical procedures.
At the beginning of treatment with Ranopril, excessive lowering of blood pressure may occur, which may subside during continued treatment and manifest as excessive fatigue and dizziness. If such symptoms occur, lie down with your legs raised, and if symptoms do not subside after several minutes, contact your doctor.
To assess treatment effectiveness 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 bruising occur, contact your doctor as soon as possible, as they may be related to a significant decrease in white blood cells or platelets.

Children and adolescents
Ranopril has been studied in children. For additional information, consult your doctor.
Lisinopril is not recommended for children under 6 years of age or for children with severe kidney function impairment.

Ranopril and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. Ranopril may affect the action of other medicines, and other medicines may affect the action of Ranopril.
In particular, inform your doctor if the patient is taking any of the following medicines:

• mTOR inhibitors (e.g. temsirolimus, syrolimus, everolimus – medicines most commonly used to prevent rejection of transplanted organs or in cancer treatment), racecadotril (used to treat diarrhoea) or vildagliptin (used to treat diabetes), as the risk of angioedema may increase (sudden swelling of subcutaneous tissue, e.g. in the throat area);
• potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole, a combination of trimethoprim and sulfamethoxazole – 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), as this increases the risk of hyperkalemia (high blood potassium levels). Your doctor may recommend dose adjustments and/or additional precautions if you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to use Ranopril" and "Warnings and precautions").

It is particularly important for your doctor to know about the use of the following when determining the appropriate dose of Ranopril: other antihypertensive medicines, diuretics (water pills), potassium-containing preparations (including salt substitutes), antidiabetic medicines (including oral antidiabetics or insulin), lithium (a medicine used to treat certain types of depression) and certain medicines used to treat pain and joint diseases.
Ranopril used together with diuretics may enhance the blood pressure-lowering effect.
Indomethacin and other non-steroidal anti-inflammatory drugs (e.g. acetylsalicylic acid) may reduce the antihypertensive effect of Ranopril.
Concomitant administration of Ranopril and lithium salts may reduce lithium excretion. Your doctor will recommend regular monitoring of serum lithium levels and, if necessary, lower doses of lithium.

Pregnancy and breastfeeding
If the patient is pregnant, 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
The use of Ranopril in pregnant women is contraindicated.
ACE inhibitors, including Ranopril, may cause fetal injury or death if taken 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, as advised, change the treatment regimen.
Women who are pregnant or planning to become pregnant should inform their doctor before starting Ranopril.
Women of childbearing potential taking lisinopril should use effective contraception.

Breastfeeding
It is not known whether lisinopril passes into human milk. The use of Ranopril in breastfeeding women is contraindicated.

Driving and operating machinery
Individual responses to the medicine may vary. Some adverse reactions reported during the use of Ranopril may affect the ability to drive or operate machinery (see section 4).

Ranopril contains mannitol
Mannitol may have a mild laxative effect.

3. How to use Ranopril

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
Ranopril should be taken once daily, at the same time each day.
Tablets may be taken before, during, or after meals. Food does not affect the action of the medicine.

Essential hypertension
In essential arterial hypertension, the usual initial dose is 10 mg once daily, with a maintenance dose of 20 mg once daily. The maximum single daily dose is 80 mg.
For patients already treated with diuretics, the doctor will usually recommend discontinuation or reduction of the diuretic dose 2–3 days before starting Ranopril therapy. The recommended initial dose is 5 mg.

Renovascular hypertension
For patients with renovascular hypertension, bilateral renal artery stenosis, or stenosis of the artery of a solitary kidney, the initial dose ranges from 2.5 mg to 5 mg once daily. The doctor may subsequently recommend a higher dose.

Heart failure
In heart failure, the initial dose is 2.5 mg once daily, with a maintenance dose ranging from 5 mg to 20 mg once daily.
If diuretics cannot be discontinued, or in dehydrated patients, patients with sodium deficiency, or renal impairment, the doctor should prescribe a lower dose of lisinopril, adjusted according to the severity of renal impairment (creatinine clearance).

Acute phase of myocardial infarction
In the acute phase of myocardial infarction, in hemodynamically stable patients (without cardiogenic shock), the doctor should prescribe the first dose of 5 mg within 24 hours of the infarction. After another 24 hours, the same dose (5 mg) should be administered, and after 48 hours from the onset of infarction, a dose of 10 mg of lisinopril. Treatment should then continue with a single daily dose of 10 mg for 6 weeks.
If there are no contraindications, the doctor will also recommend the 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 lisinopril once daily, both at the beginning of treatment and during the following three days. If hypotension occurs (systolic blood pressure below 100 mmHg), the doctor 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 doctor should recommend discontinuation of Ranopril.

Diabetic nephropathy
In patients with hypertension and insulin-independent diabetes (type 2), the usual single initial daily dose of Ranopril is 10 mg. The maintenance daily dose should be adjusted so as to reduce diastolic blood pressure in the sitting position to values currently recommended 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 hypertension
The doctor will determine the dose appropriate for the child, which 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.

Taking more Ranopril than recommended
If a patient takes more Ranopril than prescribed, they should immediately contact a doctor. Medical observation is necessary. The most likely symptom of overdose is excessive lowering of blood pressure and associated dizziness.

Missing a dose of Ranopril
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, the patient should resume taking the medicine regularly at the dose recommended by the doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Ranopril is generally well tolerated. Common side effects include dizziness,
headache, diarrhoea, vomiting, kidney function disorders, cough, and dizziness related to
a sudden drop in blood pressure when standing up quickly (orthostatic symptoms). Other
side effects that occur not infrequently include myocardial infarction or
cerebrovascular incident, probably secondary to excessive lowering of blood pressure in patients at high risk,
palpitations (feeling of strong heartbeat), rapid heart rate (tachycardia), reduced blood flow in the fingers and toes,
manifesting as a change in their colour, accompanied by a sensation of coldness or numbness (Raynaud's phenomenon),
nasal mucosal inflammation, abdominal pain, indigestion, nausea, rash, itching, weakness,
mood disturbances, sleep disturbances, tingling, tickling sensation, pricking or burning sensation (paresthesia),
impotence, fatigue, dizziness, taste disturbances, increased blood urea concentration,
increased serum creatinine concentration, increased liver enzyme activity,
elevated blood potassium levels (hyperkalemia).

Other side effects occurring rarely include: decreased haemoglobin concentration, reduced proportion of red blood cells (decreased haematocrit value), disorientation, dryness of the oral mucosa, hypersensitivity/angioedema (swelling of the face, limbs, lips, tongue, glottis and (or) larynx), urticaria, hair loss (alopecia), excessive urea, creatinine and other nitrogenous end products of protein and amino acid metabolism in the blood (uraemia), acute renal failure, gynaecomastia, increased serum bilirubin concentration, low blood potassium levels (hypokalaemia).

Other side effects may also occur very rarely and some of them may be severe. Examples of such side effects include yellowing of the skin and (or) eyes (jaundice), oliguria or anuria, and severe abdominal pain. Other very rare side effects include: bone marrow suppression, anaemia, low platelet count (thrombocytopenia), reduced total white blood cell count (leukopenia), low neutrophil count (neutropenia), marked reduction in granulocytes (agranulocytosis), haemolytic anaemia, enlarged lymph nodes (lymphadenopathy), autoimmune disease, low blood sugar (hypoglycaemia), airway constriction (bronchospasm), sinusitis, pancreatitis, intestinal wall oedema (intestinal angioedema), liver inflammation (hepatocellular or cholestatic), liver failure, excessive sweating, blistering of the skin and mucous membranes (bullous eruption), blistering and peeling of the skin (toxic epidermal necrolysis), Stevens-Johnson syndrome, erythema multiforme.

The following side effects have also been reported, but their frequency cannot be determined from the available data (frequency unknown): gout, decreased libido, depression, somnolence, stroke, fainting, angina pectoris, cardiac arrhythmias, shortness of breath, pulmonary infiltrates, laryngitis, bronchitis, nasal mucosal congestion, sore throat, anorexia, constipation, bloating, photosensitivity, pseudolymphoma of the skin, urinary tract infection, chest pain, redness, syndrome of inappropriate antidiuretic hormone secretion (SIADH), blurred vision, back pain, joint pain, muscle cramps and shoulder pain.

A syndrome involving one or more of the following symptoms has been reported: fever, vasculitis, muscle pain, joint pain or arthritis, positive antinuclear antibody (ANA) titre, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or other skin symptoms.

For additional information on side effects, please consult your doctor or pharmacist.
If any side effects or worrying symptoms occur, inform your doctor or pharmacist.

Discontinue Ranopril and seek immediate medical attention from a doctor in any of the following cases:

• if swelling of the face, lips, tongue, glottis and (or) throat occurs, which may cause
  difficulty in breathing or swallowing

• if swelling of the 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 side effects
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting of side effects helps to provide more information on the safety of the medicine.

5. How to store Ranopril

The medicine should be stored at a temperature below 25 °C. Protect from moisture.
The medicine should be stored in a place invisible and inaccessible to children.
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.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Ranopril contains
The active substance is lisinopril (in the form of lisinopril dihydrate). One tablet of Ranopril contains 5 mg, 10 mg or 20 mg of lisinopril (as lisinopril dihydrate).

• Other ingredients are: mannitol, anhydrous calcium hydrogen phosphate, maize starch, pregelatinized maize starch, magnesium stearate, yellow iron oxide, red iron oxide (Ranopril 20 mg).

What Ranopril looks like and contents of the pack
Ranopril 5 mg tablets
Light yellow, capsule-shaped, biconvex, uncoated tablets with an embossed "5" on one side of the break line and a deep score line on the other side of the tablet.
Ranopril 10 mg tablets
Light yellow, capsule-shaped, biconvex, uncoated tablets with an embossed "1" and "0" on one side of the break line and a deep score line on the other side of the tablet.
Ranopril 20 mg tablets
Light peach-coloured, capsule-shaped, biconvex, uncoated tablets with an embossed "2" and "0" on one side of the break line and a deep score line on the other side of the tablet.
Pack contains 28 tablets.

Marketing Authorisation Holder
Ranbaxy (Poland) Sp. z o.o.
Idzikowskiego Street 16
00-710 Warsaw, Poland

Manufacturer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH, Hoofddorp,
The Netherlands