Alapril

Patient Information Leaflet

Alapril 5 mg tablets, 20 mg tablets

Lisinopril
Please read all of this leaflet carefully before taking this medicine, as 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 other people, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Alapril is and what it is used for

Alapril contains the active substance lisinopril. This belongs to a group of medicines called 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.
Alapril is indicated:

• for the treatment of high blood pressure (hypertension);
• for the treatment of heart failure, a condition in which the heart does not adequately pump blood around the body;
• in combination with other therapeutic measures, for the preventive treatment of left ventricular dysfunction or heart failure and to improve survival, in patients with stable blood flow who have had a heart attack (acute myocardial infarction) within the first 24 hours.

2. What you should know before taking Alapril

Do not take Alapril if:

• you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• you have previously experienced, after taking an ACE inhibitor, a hypersensitivity reaction (allergic reaction) causing a rash similar to hives, accompanied by swelling of the hands, feet, ankles, or even of the face, lips, tongue and/or throat, leading to difficulty swallowing or breathing (angioedema);
• you suffer from hereditary angioedema (due to familial predisposition), a very rare but serious genetic disorder that may cause sudden swelling of the face, arms, legs, hands, feet, genitals, digestive tract, or airways;
• you suffer from idiopathic angioedema, i.e. angioedema of unknown cause;
• you are in the second or third trimester of pregnancy (see section “Pregnancy and breastfeeding”);
• you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
• you are taking or have recently taken 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).

If you are taking any of the following medicines, 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.

Warnings and precautions
Talk to your doctor or pharmacist before taking Alapril if:

• you are at risk of a significant drop in blood pressure due to excessive fluid loss, for example if you are taking medicines that increase urine production (diuretics), or are on a low-salt diet, or have experienced vomiting or diarrhoea. A drop in blood pressure may also occur if you have renin-dependent high blood pressure;
• you are undergoing dialysis (blood purification therapy);
• you have low blood pressure (hypotension), which may manifest as weakness or dizziness. Excessive lowering of blood pressure can be dangerous, especially in patients with impaired blood flow to the heart (ischaemic heart disease) or brain (ischaemic cerebrovascular disease);
• you have heart failure and your blood pressure is normal or low. Treatment with Alapril may cause further hypotension. This is more likely if you have severe heart failure;
• you suffer from heart valve disease, narrowing (stenosis) of the heart valve (mitral valve), narrowing (stenosis) of the aortic artery, or thickening of the heart walls (hypertrophic cardiomyopathy);
• you have a kidney disease (renal failure) or narrowing (stenosis) of one or both renal arteries;
• you have high blood sugar levels (diabetes);
• you require a blood separation treatment (apheresis), e.g. for high cholesterol levels. Your doctor may temporarily stop Alapril treatment to prevent a possible severe allergic reaction;
• you are undergoing dialysis;
• you are receiving or are scheduled to receive treatment to reduce the effects of an allergy, such as an insect sting (desensitisation treatment). If you take Alapril during this treatment, you may develop a severe allergic reaction;
• any member of your family has ever experienced (for any reason) a hypersensitivity reaction (allergic reaction) causing swelling of the hands, feet, ankles, face, lips, tongue and/or throat;
• you experience changes in blood cell counts (white blood cells, red blood cells, platelets) or a significant decrease in a certain type of infection-fighting white blood cells (agranulocytosis), especially if you have a connective tissue disease (collagenosis) affecting blood vessels or are taking medicines that suppress the immune system (immunosuppressants);
• you are scheduled for surgery requiring anaesthesia;
• you are of black race, as Alapril may be less effective and you may be at increased risk of angioedema;
• you have developed a persistent dry cough for a prolonged period after starting treatment with an ACE inhibitor. Discuss this with your doctor;
• you have high potassium levels in the blood (hyperkalaemia – see section “Alapril and other medicines”);
• you are in the first trimester of pregnancy or during breastfeeding (see section “Pregnacy and breastfeeding”);
• you are taking any of the following medicines used to treat 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 lithium (see section “Alapril and other medicines”).

Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals. See also the information under the section "Do not take Alapril".
Stop taking Alapril and contact 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;
• yellowing of the skin or whites of the eyes (jaundice), indicating possible liver problems;
• increased levels of transaminases (liver enzymes) in the blood.

Children and adolescents
The use of Alapril is not recommended in children due to lack of data on safety and efficacy.
Other medicines and Alapril
Inform your doctor if you are taking, have recently taken, or might take any other medicine.
In particular, talk to your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines:

• potassium supplements (including salt substitutes), diuretics (including potassium-sparing diuretics), and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole used to treat bacterial infections; ciclosporin, an immunosuppressive medicine used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood and prevent clot formation);
• other medicines for the treatment of high blood pressure;
• non-steroidal anti-inflammatory drugs (NSAIDs), used to treat joint inflammation (arthritis) or muscle pain;
• lithium, used to treat manic-depressive disorders; concomitant use is not recommended, but if combination therapy is necessary, your doctor may monitor your blood lithium levels;
• an mTOR inhibitor (e.g. temsirolimus), used to treat certain types of cancer;
• alteplase, used to treat acute myocardial infarction and acute ischaemic stroke;
• insulin or other oral antidiabetic medicines, such as vildagliptin. Blood glucose levels should be closely monitored during the first weeks of Alapril treatment, especially in patients with kidney problems;
• antipsychotics and tricyclic antidepressants, used to treat mental disorders;
• gold-containing medicines, such as sodium aurothiomalate, which may be administered by injection and used to treat arthritis;
• an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "Do not take Alapril" and "Warnings and precautions"). Your doctor may need to adjust your dose and/or take other precautions;
• anaesthetics;
• medicines acting on the autonomic nervous system (sympathomimetics), such as ephedrine, pseudoephedrine, salbutamol, found in some nasal decongestants, cough and cold remedies, and asthma medicines;
• high doses of acetylsalicylic acid (aspirin);
• nitrates (such as nitroglycerin) or other vasodilators, used to treat heart conditions;
• medicines used to suppress the immune system response (immunosuppressants);
• allopurinol, used to treat gout;
• procainamide, used to treat heart rhythm disorders.

Alapril with food and drinks
Food and drinks do not affect the absorption of Alapril. You may take Alapril before, during, or after meals.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Alapril is not recommended during the first three months of pregnancy. Do not take Alapril 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 you to stop taking Alapril and prescribe an alternative treatment.
Breastfeeding
Alapril is not recommended during breastfeeding. Inform your doctor if you are breastfeeding or intend to breastfeed. Your doctor may prescribe an alternative treatment during breastfeeding, especially if your baby is a newborn or premature.
Driving and using machines
Alapril may cause dizziness or unusual tiredness; therefore, exercise particular caution before driving or operating machinery.

3. How to take Alapril

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Instructions for use
Swallow the tablet with a small amount of water.
Take the tablets at the same time each day. You may choose whether to take the tablets before, during, or after meals.
Pay particular attention when taking your first dose of Alapril, as you may experience a greater drop in blood pressure than occurs later during treatment, especially if you suffer from high blood pressure. This may cause dizziness or a feeling of lightheadedness. If this happens, lying down may help.
This is more likely to occur if you are taking another medicine that promotes diuresis (a diuretic). In such a case, your doctor will instruct you to stop taking the diuretic 2 or 3 days before starting treatment with Alapril.
Use in adults
For the treatment of high blood pressure (arterial hypertension):
The recommended initial dose is 10 mg once daily. Your doctor will gradually increase the dose to achieve the best possible control of your blood pressure. The recommended maintenance dose is 20 mg once daily. The maximum dose studied in humans during long-term treatment is 80 mg once daily.
For the treatment of heart failure:
The recommended initial dose is 2.5 mg once daily. Your doctor will gradually increase the dose every 2–4 weeks, or more rapidly if deemed necessary.
The maintenance dose ranges from 5 to 20 mg once daily.
For the treatment of patients who have had a heart attack (myocardial infarction):
The recommended dose is 5 mg within 24 hours of the heart attack, followed by 5 mg on the following day.
The maintenance dose is 10 mg once daily. Your doctor may adjust the dosage according to your blood pressure values.
You must take the medicine for at least 6 weeks.
Use in children and adolescents
Alapril is not recommended for use in children due to lack of data on safety and efficacy.
Use in elderly patients and patients with renal impairment
If you are elderly, have kidney problems, or are taking diuretics, your doctor may prescribe a lower dose than the recommended one. Your doctor may adjust the dose based on your blood pressure response to treatment.
If you take more Alapril than you should
In case of accidental ingestion or overdose of Alapril, contact your doctor immediately or go to the nearest hospital.
An overdose may cause one or more of the following symptoms: low blood pressure (hypotension), reduced blood and oxygen supply to tissues (circulatory shock), disturbances in the concentration of electrolytes in blood and body fluids, kidney problems (renal failure), increased breathing rate (hyperventilation), increased heart rate (tachycardia), palpitations, dizziness, anxiety, and cough.
If you forget to take Alapril
Do not take a double dose to make up for the missed dose. Continue taking Alapril according to your usual schedule.
If you stop taking Alapril
Do not stop taking the tablets, even if you feel well, unless otherwise instructed by your doctor.
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 Alapril 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 itching of the skin, accompanied by localized swelling;
• yellowing of the skin and whites of the eyes (jaundice);
• increased levels of liver enzymes.

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.
Common side effects (may affect up to 1 in 10 people)

• dizziness;
• headache (cephalalgia);
• posture-related effects (orthostatic), including low blood pressure (hypotension);
• cough;
• diarrhoea, vomiting;
• kidney problems (renal dysfunction).

Uncommon side effects (may affect up to 1 in 100 people)

• mood changes; numbness or tingling of limbs, arms and legs (paraesthesia); loss of balance (dizziness); altered taste; drowsiness, insomnia and unusual dreams, hallucinations;
• myocardial infarction or diseases affecting the nervous and circulatory systems (cerebrovascular events), following hypotension in individuals at higher risk; sensation of pounding heartbeat (palpitations); increased heart rate (tachycardia); change in skin colour (bluish followed by redness) and/or numbness or tingling of fingers and toes (Raynaud's disease);
• inflammation of the nasal mucosa (rhinitis);
• feeling unwell (nausea); stomach pain or indigestion;
• skin rash; itching; hypersensitivity reactions with sudden swelling of hands, feet, ankles, face, lips, tongue and/or throat, leading to difficulty swallowing and breathing (angioedema);
• inability to achieve an erection (erectile dysfunction);
• feeling of fatigue; loss of strength (asthenia);
• increased blood levels of nitrogen, creatinine, liver enzymes and potassium.

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

• 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);
• mental confusion, disturbances in the sense of smell;
• dry mouth;
• nodular skin rash (urticaria); hair loss (alopecia); chronic, i.e. persistent and long-lasting, inflammation of the skin (psoriasis);
• increased blood urea levels (uraemia); severe kidney problems (renal failure);
• breast development in men (gynaecomastia);
• syndrome of inappropriate antidiuretic hormone secretion (SIADH);
• increased blood levels of bilirubin;
• reduced sodium levels in the blood (hyponatraemia).

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

• reduced bone marrow function; deficiency of red blood cells (anaemia); reduced platelet count (thrombocytopenia); decreased white blood cell count (neutropenia, leucopenia); reduction in white blood cells (agranulocytosis); destruction of red blood cells (haemolytic anaemia) – increasing the likelihood of infections; enlarged lymph nodes (lymphadenopathy); diseases causing the body to mount an immune response against itself (autoimmune diseases);
• low blood sugar levels (hypoglycaemia);
• narrowing of the bronchi (bronchospasm); sinusitis; allergic inflammation of lung alveoli (alveolitis); pneumonia caused by accumulation of white blood cells in the lung;
• inflammation of the pancreas (pancreatitis); intestinal angioedema; inflammation of the liver (hepatitis), affecting either liver cells or bile ducts (hepatocellular and cholestatic hepatitis); yellowing of the skin and whites of the eyes (jaundice); liver problems (hepatic failure);
• sweating; autoimmune disease affecting the skin and/or mucous membranes (pemphigus); severe skin disease characterized by destruction of the skin epithelium and mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis); inflammation causing erythematous skin lesions associated with blood vessel inflammation (erythema multiforme); transient enlargement of cutaneous lymph nodes (cutaneous pseudolymphoma);
• reduced (oliguria) or absent (anuria) urine output.

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• depressive symptoms; transient loss of consciousness (fainting);
• fluid accumulation in the extremities (peripheral oedema);
• chest pain;
• joint pain;
• fever.

Other side effects
A complex disorder including one or more of the following symptoms has been reported:

• fever;
• inflammation of blood vessels (vasculitis);
• muscle pain (myalgia);
• joint inflammation (arthralgia/arthritis);
• positive test for antinuclear antibodies;
• elevated erythrocyte sedimentation rate;
• elevated levels of eosinophils and leucocytes in the blood;
• skin rash;
• sensitivity to light (photosensitivity);
• other dermatological manifestations.

Reporting of side effects
If you get any side effects, including ones 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 Alapril

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.
The stated expiry date applies to the medicine stored in its original intact packaging and kept under proper storage conditions.
This medicine requires no 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 Alapril contains
The active substance is lisinopril dihydrate.
5 mg tablets
Each 5 mg Alapril tablet contains 5.445 mg of lisinopril dihydrate (equivalent to 5 mg of anhydrous lisinopril).
The other components are: mannitol, calcium hydrogen phosphate, maize starch, pregelatinized starch, magnesium stearate.
20 mg tablets
Each 20 mg Alapril tablet contains 21.78 mg of lisinopril dihydrate (equivalent to 20 mg of anhydrous lisinopril).
The other components are: mannitol, calcium hydrogen phosphate, maize starch, pregelatinized starch, magnesium stearate, red iron oxide, yellow iron oxide.

Description of the appearance of Alapril and contents of the pack
Alapril is presented as tablets contained in PVC/aluminum blisters.
Alapril 5 mg tablets are available in packs containing 14 or 28 tablets.
Alapril 20 mg tablets are available in packs containing 14 or 28 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization 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 (LO), Italy.