Enapren

PACKAGE LEAFLET

Package leaflet: information for the user

Enapren 5 mg or 20 mg tablets

enalapril maleate
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, consult 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, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Enapren is and what it is used for

Enapren contains an active substance called enalapril maleate. This active substance belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors).
Enapren is used:

• to treat high blood pressure (hypertension)
• to treat heart failure (weakening of heart function). It can reduce the need for hospitalisation and may help some patients live longer
• to prevent signs of heart failure. These signs include: shortness of breath, tiredness after light physical activity such as walking, or swelling of the ankles and feet. This medicine works by widening your blood vessels. This lowers your blood pressure. The medicine usually starts to work within one hour, and the effect lasts for at least 24 hours. Some people may need several weeks of treatment before the full effect on blood pressure can be seen.

2. What you should know before taking Enapren

Do not take Enapren

• if you are allergic to enalapril maleate or to any of the other ingredients of this medicine (listed in section 6)
• if you previously had an allergic reaction to a medicine of the same type as this one, called an ACE inhibitor
• if you previously experienced swelling of the face, lips, mouth, tongue, or throat causing difficulty in swallowing or breathing (angioedema) of unknown or hereditary origin
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren
• if you are more than 3 months pregnant. (It is also preferable to avoid using Enapren during early pregnancy – see section Pregnancy.)
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, because the risk of angioedema (rapid swelling under the skin, for example in the throat) is increased

Do not take this medicine if you have any of the above conditions. If you are unsure,
speak with your doctor or pharmacist before taking this medicine.
Warnings and precautions
Talk to your doctor or pharmacist before taking Enapren:

• if you have a heart condition
• if you have a condition affecting the blood vessels in the brain
• if you have a blood disorder such as low number or absence of white blood cells (neutropenia/agranulocytosis), low platelet count (thrombocytopenia), or reduced number of red blood cells (anemia)
• if you have a liver problem
• if you have a kidney problem (including kidney transplant), follow a low-salt diet, are taking potassium supplements, potassium-sparing agents, potassium-containing salt substitutes, or other medicines that may increase potassium levels in the blood (e.g., heparin [a medicine used to prevent blood clots], products containing trimethoprim such as co-trimoxazole [medicines used to treat infections]). This may lead to increased potassium levels in the blood, which can be serious. Your doctor may need to adjust your dose of Enapren or monitor your blood potassium levels. See also information in section “Other medicines and Enapren”
• if you are on dialysis
• if you have recently experienced excessive vomiting or severe diarrhea
• if you have diabetes. Close monitoring for low blood glucose levels is necessary, especially during the first month of treatment. Blood potassium levels may also be higher
• if you previously had an allergic reaction with swelling of the face, lips, tongue, or throat causing difficulty in swallowing or breathing. You should know that black patients are at higher risk for these types of reactions to ACE inhibitors
• if you have low blood pressure (you may notice this as dizziness or feeling faint, especially when standing up)
• if you have a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma), are undergoing immunosuppressive therapy, or are taking allopurinol, procainamide, or their combinations
• if you are taking any of the following medicines, the risk of angioedema may be increased:
  • racecadotril, a medicine used to treat diarrhea
  • medicines used to prevent organ transplant rejection or for cancer (e.g., temsirolimus, sirolimus, everolimus)
  • vildagliptin, a medicine used to treat diabetes
• if you are taking any of the following medicines for high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA) (also known as sartans – for example valsartan, telmisartan, irbesartan, etc.), particularly if you have kidney problems related to diabetes
  • aliskiren

Your doctor may check your kidney function, blood pressure, and levels of electrolytes
(e.g., potassium) in your blood at regular intervals.
See also the information under “Do not take Enapren”.
You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming
pregnant). This medicine is not recommended during early pregnancy and must not be taken if you are
more than 3 months pregnant, as it may cause severe harm to the unborn child if taken during this time (see section Pregnancy).
You should know that in black patients, this medicine reduces blood pressure less effectively than in non-black patients.
If you are unsure whether any of the above conditions apply to you, consult your doctor or pharmacist
before taking this medicine.
If you are about to undergo a procedure
If you are about to undergo any of the following procedures, inform your doctor that you are taking
Enapren:

• any type of surgery or anesthesia (including dental anesthesia)
• a treatment that removes cholesterol from the blood called “LDL apheresis”
• desensitization treatment to reduce the effects of an allergy to bee or wasp stings. If any of the above conditions apply to you, talk to your doctor or dentist before the procedure.

Other medicines and Enapren
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines. This is because Enapren may interfere with the way some medicines work. Also, some other medicines may interfere with the way Enapren works. Your doctor may need to adjust the dose and/or take other precautions.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also information under “Do not take Enapren” and “Warnings and precautions”)
• other medicines to lower blood pressure, such as beta-blockers or diuretics
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; heparin, a medicine used to thin the blood to prevent clotting). See also information in section “Warnings and precautions”
• medicines for diabetes (including oral antidiabetics and insulin)
• lithium (a medicine used to treat certain types of depression)
• medicines for depression called “tricyclic antidepressants”
• medicines for mental disorders called “antipsychotics”
• some cough and cold medicines and weight-reducing medicines containing a so-called “sympathomimetic agent”
• some medicines for pain or arthritis, including gold salts therapy
• an mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus: medicines used to treat certain types of cancer or to prevent rejection of a transplanted organ by the body’s immune system). See also information in section “Warnings and precautions”
• a medicine containing a neprilysin inhibitor such as sacubitril (available as a fixed-dose combination with valsartan), racecadotril, or vildagliptin. The risk of angioedema (swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing) may be increased. See also information in sections “Do not take Enapren” and “Warnings and precautions”
• non-steroidal anti-inflammatory medicines, including COX-2 inhibitors (medicines that reduce inflammation and may be used to help relieve pain)
• aspirin (acetylsalicylic acid)
• medicines used to dissolve blood clots (thrombolytics)
• alcohol. If you are unsure whether any of the above conditions apply to you, speak with your doctor or pharmacist before taking Enapren.

Enapren with food and drink
Enapren can be taken with or without food. Most people take Enapren with a glass of water.
Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before taking this medicine. Your doctor will usually advise you to stop taking Enapren before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. This medicine is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause severe harm to the unborn child if taken after the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to start breastfeeding. Breastfeeding is not recommended for newborns (first weeks after birth), especially premature infants, while taking this medicine. For older infants, your doctor will advise you on the benefits and risks of taking this medicine during breastfeeding compared to other treatments.
Driving and using machines
Dizziness or drowsiness may occur while taking this medicine. If this happens, do not drive or operate tools or machinery.
Enapren contains lactose
Enapren contains lactose, which is a type of sugar. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Enapren contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take Enapren

Always take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.

• It is very important to keep taking this medicine for as long as prescribed by your doctor.
• Do not take more tablets than prescribed.
• The break line is intended to facilitate splitting the tablet if you have difficulty swallowing it whole.

High blood pressure

• The usual initial dose ranges from 5 to 20 mg once daily.
• Some patients may need to start treatment with a lower dose.
• The usual maintenance dose is 20 mg once daily.
• The maximum maintenance dose is 40 mg once daily.

Heart failure

• The usual initial dose is 2.5 mg once daily.
• Your doctor will gradually increase the dose until the appropriate dose for you is reached.
• The usual maintenance dose is 20 mg per day, taken in one or two doses.
• The maximum maintenance dose is 40 mg per day, divided into two doses.

Patients with kidney problems
The dose of the medicine will vary depending on the function of your kidneys:

• moderate kidney problems - 5 to 10 mg per day,
• severe kidney problems - 2.5 mg per day,
• if you are on dialysis - 2.5 mg per day. On days when you are not undergoing dialysis, the dose may be adjusted according to your blood pressure.

Elderly patients
The dose will be determined by your doctor and will be based on the degree of kidney function.
Use in children
Experience with the use of Enapren in children with high blood pressure is limited. If the child is
able to swallow tablets, the dose will be determined based on the child's weight and blood pressure.
The usual initial doses are:

• weight between 20 kg and 50 kg - 2.5 mg per day,
• weight above 50 kg - 5 mg per day. The dose may be adjusted according to the child's needs:
• a maximum dose of 20 mg per day may be used in children weighing between 20 kg and 50 kg,
• a maximum dose of 40 mg per day may be used in children weighing above 50 kg.

This medicine is not recommended for newborns (first weeks of life) and children with
kidney problems.
If you take more Enapren than you should
If you take more Enapren than you should, inform your doctor or go to hospital immediately. Take
the medicine pack with you. The following effects may occur: feeling of light-headedness or dizziness. This is due to a sudden or excessive drop in blood pressure.
If you forget to take Enapren

• If you forget to take a tablet, skip the missed dose.
• Take the next dose as usual.
• Do not take a double dose to make up for the missed dose.

If you stop taking Enapren
Do not stop treatment with this medicine unless your doctor tells you to.
If you have any doubts about how to use 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. The following side effects may occur with this medicine:
Stop taking Enapren and contact a doctor immediately if you notice any of the following:

• swelling of the face, lips, tongue or throat, which may cause difficulty breathing or swallowing
• swelling of the hands, feet or ankles
• development of a rash with raised red patches (urticaria).

You should be aware that black patients have a higher risk of developing these types of reactions. If you notice any of these symptoms, stop taking Enapren and contact a doctor immediately.
When you start taking this medicine, you may feel faint or dizzy. If this happens, lying down may help. This is caused by a drop in blood pressure. The symptoms should improve as you continue taking the medicine. If you are concerned, please contact your doctor.

Other side effects include:
Very common (may affect more than 1 in 10 people)

• dizziness, weakness or feeling unwell
• blurred vision
• cough

Common (may affect up to 1 in 10 people)

• confusion due to low blood pressure, changes in heart rate, rapid heartbeat, angina or chest pain
• headache, depression, fainting (syncope), altered taste sensation
• shortness of breath
• diarrhoea, abdominal pain
• tiredness (fatigue)
• skin rash, allergic reactions with swelling of the face, lips, tongue or throat causing difficulty breathing or swallowing
• high levels of potassium in the blood, increased levels of creatinine in the blood (both usually detected by laboratory tests)

Uncommon (may affect up to 1 in 100 people)

• flushing
• sudden drop in blood pressure
• rapid or irregular heartbeat (palpitations)
• heart attack (possibly due to very low blood pressure in some high-risk patients, including those with circulatory problems affecting the heart or brain)
• stroke (possibly due to very low blood pressure in high-risk patients)
• anaemia (including aplastic and haemolytic anaemia)
• confusion, insomnia or drowsiness, nervousness
• sensation of tingling or numbness of the skin
• vertigo (sensation of dizziness)
• ringing in the ears (tinnitus)
• runny nose, sore throat or hoarseness
• slowed movement of food through the intestine (ileus), inflammation of the pancreas
• feeling unwell (nausea), indigestion, constipation, loss of appetite
• irritated stomach (gastric irritation), dry mouth, ulcer
• muscle cramps
• impaired kidney function, kidney failure
• increased sweating
• itching or urticaria
• hair loss
• general feeling of being unwell, high body temperature (fever)
• impotence
• high levels of protein in the urine (detected by laboratory test)
• low levels of sugar or sodium in the blood, high levels of urea in the blood (all detected by blood tests)

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

• “Raynaud’s phenomenon”, in which hands and feet may become very cold and white due to reduced blood flow
• changes in blood values such as decreased number of white blood cells and red blood cells, decreased haemoglobin, decreased number of platelets
• bone marrow depression
• swelling of the glands in the neck, armpits or groin
• autoimmune diseases
• unusual dreams or sleep disturbances
• accumulation of fluid or other substances in the lungs (detected by X-ray)
• inflammation of the nose
• inflammation of the lungs causing breathing difficulties (pneumonitis)
• inflammation of cheeks, gums, tongue, lips, throat
• decreased urine output
• target-like skin rash (erythema multiforme)
• “Stevens-Johnson syndrome” and “toxic epidermal necrolysis” (serious skin conditions causing redness, peeling of the skin, blistering or raw areas), exfoliative dermatitis/erythroderma (severe skin rash with peeling or shedding of the outer layer of skin), pemphigus (small fluid-filled blisters on the skin)
• liver or gallbladder problems such as reduced liver function, inflammation of the liver, jaundice (yellowing of the skin or eyes), high levels of liver enzymes or bilirubin (detected by blood tests)
• breast enlargement in men (gynaecomastia)

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

• swelling in the intestine (intestinal angioedema)

Not known (frequency cannot be estimated from the available data)

• excessive production of antidiuretic hormone, causing fluid retention, leading to weakness, tiredness or confusion
• a complex of symptoms has been reported which may include some or all of the following: fever, inflammation of blood vessels (serositis/vasculitis), muscle pain (myalgia/myositis), joint pain (arthralgia/arthritis). Skin rash, photosensitivity or other skin manifestations may also occur.

Reporting of side effects
If you experience any side effects, 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 Enapren

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister pack and carton after the word "EXP". The expiry date refers to the last day of that month.
Do not store above 25°C. Keep in the original packaging to protect the medicine from moisture.
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 Enapren contains

• The active substance is enalapril maleate (5 mg or 20 mg).
• The other ingredients are monohydrate lactose, sodium bicarbonate, corn starch, pregelatinized corn starch, magnesium stearate. The 20 mg tablets also contain red iron oxide (E172) and yellow iron oxide (E172).

Description of the appearance of Enapren and contents of the pack
Enapren is available in the following pack sizes:
ENAPREN 5 mg – aluminium blister packs containing 2, 14, 20, 28, 28 x 1, 30, 49 x 1,
50, 56, 98 or 100 tablets.
ENAPREN 20 mg – aluminium blister packs containing 10, 14, 20, 28, 28 x 1, 30, 49 x 1,
50, 56, 60, 84, 90, 98, 100 or 500 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Organon Italia S.r.l.
Piazza Carlo Magno, 21
00162 Rome
Italy

Manufacturers
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium

N.V. Organon
Kloosterstraat 6
5349 AB Oss
The Netherlands

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following brand names:
Austria, Belgium, Finland, France, Greece, Luxembourg, The Netherlands, Portugal, Spain, Sweden:
RENITEC
Germany:
XANEF
Italy:
ENAPREN
United Kingdom (Northern Ireland), Ireland:
INNOVACE