Enalapril and hydrochlorothiazide Hexal AG: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE USER

ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG 20 mg + 6 mg tablets

Generic medicine
Please read all of this leaflet carefully before you start 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, 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, because it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG is and what it is used for
What you need to know before taking ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
How to take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
Possible side effects
How to store ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
Contents of the pack and other information

1. What Enalapril Hydrochlorothiazide Hexal AG is and what it is used for

Enalapril belongs to a group of medicines called "angiotensin-converting enzyme inhibitors" (ACE inhibitors) and lowers blood pressure by widening blood vessels.
Hydrochlorothiazide belongs to a group of medicines called "diuretics" and reduces blood pressure by increasing diuresis (urine output).
ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG contains a combination of enalapril and hydrochlorothiazide and is used to treat hypertension when treatment with enalapril alone has proven insufficient.
Your doctor may also prescribe this medicine instead of a similar combination of separate doses of enalapril and hydrochlorothiazide.
This fixed-dose combination is not suitable for initial therapy.
Contact your doctor if you do not feel better or if you feel worse.

2. What you need to know before taking Enalapril Hydrochlorothiazide Hexal AG

Do not take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG

if you are allergic to enalapril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6);
if you are allergic to other medicines in the same class as this medicine (ACE inhibitors) or to other sulfonamide-derived drugs (mostly antibiotics such as sulfamethoxazole);
if you have previously been treated with a medicine in the same class as this one (ACE inhibitors) and experienced allergic reactions with swelling of the face, lips, tongue, and/or throat, accompanied by difficulty swallowing or breathing. Do not take this medicine if you have had such reactions without a known cause, or if any of your blood relatives have previously experienced such allergic reactions (you have been diagnosed with hereditary or idiopathic angioedema);
if you suffer from severe kidney problems;
if you have problems urinating;
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
if you suffer from severe liver disorders;
if you are more than 3 months pregnant (it is also advisable to avoid Enalapril Hydrochlorothiazide Hexal AG in early pregnancy – see section on Pregnancy).

Warnings and precautions
Talk to your doctor or pharmacist before taking Enalapril Hydrochlorothiazide Hexal AG:

if you suffer from narrowing of the arteries (arteriosclerosis), or cerebrovascular disorders such as stroke or transient ischemic attack (TIA, also known as "mini-stroke");
if you suffer from a disease characterized by reduced blood supply to the heart muscle, usually due to coronary artery disease (ischemic heart disease);
if you suffer from heart failure;
if you have low blood pressure, are on a low-salt diet, or are taking diuretics;
if you have abnormal levels of water and electrolytes in your body (fluid/electrolyte imbalance), characterized by nausea, abdominal cramps and/or vomiting, headache, edema (swelling), muscle weakness and/or tremors, among others;
if you suffer from a heart muscle disease (hypertrophic cardiomyopathy), narrowing of the aorta (the main artery carrying blood from the heart, known as aortic stenosis), or other forms of cardiac outflow obstruction;
if you are scheduled to undergo LDL apheresis (removal of cholesterol from the blood using special equipment);
if you are scheduled to undergo desensitization therapy for insect venom, such as bee or wasp stings;
if you have diabetes and are taking antidiabetic medicines (you should monitor your blood for low glucose levels, especially during the first month of treatment);
if you suffer from gout, have high levels of uric acid in the blood, or are being treated with allopurinol;
if you are about to undergo anesthesia (including dental anesthesia);
if you have recently experienced prolonged and severe vomiting and/or severe diarrhea;
if you are scheduled to undergo tests to assess your parathyroid function;
if you suffer from or have suffered from kidney or liver problems, narrowing of the renal arteries (renal artery stenosis), have only one functioning kidney, or are undergoing hemodialysis;
if you suffer from collagen vascular diseases such as systemic lupus erythematosus (SLE) or scleroderma, which may be associated with skin rash, joint pain, and fever;
if you are receiving immunosuppressive therapy or are taking procainamide, used among others for treating cardiac arrhythmias;
if you have previously had skin cancer or develop unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV rays while taking Enalapril Hydrochlorothiazide Hexal AG;
if you suffer from allergies or asthma;
if you are taking lithium, a medicine used to treat certain psychiatric disorders;
if you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin, for example in the throat) is increased:
sirolimus, everolimus, temsirolimus, and other medicines belonging to the mTOR inhibitor class (used to prevent organ transplant rejection);
if 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), especially if you have kidney problems related to diabetes;
aliskiren.

Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g., potassium) in your blood at regular intervals.
See also the section "Do not take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG".

Inform your doctor if you think you may be pregnant (or could become pregnant). ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG is not recommended during early pregnancy and must not be used after the first trimester, as it may seriously harm the unborn child (see "Pregnancy"). ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG is generally not recommended in the following cases; therefore, consult your doctor before taking this medicine:
if you have recently undergone a kidney transplant;
if you have high levels of potassium in your blood, your potassium levels should be monitored during treatment. Risk factors for elevated potassium levels include impaired kidney function, age (>70 years), dehydration, acute heart failure, acidification of the blood (metabolic acidosis), diabetes (diabetes mellitus), concomitant use of potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, or use of medicines that increase blood potassium levels. You may also develop low potassium levels, characterized by high blood pressure, cardiac arrhythmias, etc. (e.g., due to drug interactions, excessive urinary loss, etc.).

Also refer to the section "Other medicines and ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG" below.
For athletes: using this medicine without therapeutic need constitutes doping and may lead to false positives in anti-doping tests.
Elderly patients (>70 years) or malnourished individuals should exercise particular caution when using this medicine.
This medicine may be less effective in Black patients.
If you experience any of the following symptoms while taking this medicine, inform your doctor immediately:

you feel dizzy after taking the first dose. Some people react to the first dose or an increased dose with symptoms such as dizziness, weakness, fainting, and nausea;
you develop sudden swelling of the lips, face, and neck, which may also affect hands and feet, or experience shortness of breath or hoarseness: these are symptoms of a condition called angioedema, which can occur at any stage of treatment. ACE inhibitors cause a higher incidence of angioedema in Black patients compared to non-Black patients;
you develop fever, sore throat, or mouth ulcers (these may be symptoms of an infection caused by a decrease in white blood cells);
you develop yellowing of the skin or whites of the eyes (jaundice), which may indicate a liver disorder;
you develop a dry, persistent cough. Cough has been reported with ACE inhibitors, but it may also be a symptom of another upper respiratory tract disorder;
sudden onset of myopia;
if you experience a decrease in vision or eye pain with redness and sudden blurring of vision. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure (glaucoma), which may occur from a few hours to weeks after taking Enalapril Hydrochlorothiazide Hexal AG. This may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing this condition.

Children and adolescents
The use of Enalapril Hydrochlorothiazide Hexal AG is not recommended in children and adolescents.
Other medicines and ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
You must not take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG at the same time as the following medicines:

potassium supplements or potassium-containing salt substitutes;
diuretics used to treat hypertension, such as furosemide, or potassium-sparing diuretics such as spironolactone, eplerenone, triamterene, or amiloride; other medicines that may increase potassium levels in the body (including heparin and cotrimoxazole, also known as trimethoprim/sulfamethoxazole);
other medicines used to treat high blood pressure;
anesthetics and medicines used for mental disorders or depression (tricyclic antidepressants), medicines used to treat psychosis or sedatives;
lithium (a medicine used to treat psychiatric disorders);
painkillers and anti-inflammatory medicines, such as acetylsalicylic acid (>300 mg/day) or indomethacin;
gold salt injections (sodium aurothiomalate), an injectable medicine used for rheumatoid arthritis;
medicines such as ephedrine (used in some cough and cold remedies), noradrenaline, or adrenaline, used for low blood pressure, shock, heart failure, asthma, or allergies;
medicines that lower blood sugar levels, such as insulin or oral antidiabetics;
colestyramine resin and colestipol, active ingredients used to lower blood lipid levels;
corticosteroids, anti-inflammatory substances similar to hormones;
corticotropin (ACTH), mainly used to assess proper adrenal gland function;
muscle relaxants (e.g., tubocurarine chloride, medicines used to relax muscles during surgery);
cancer treatments such as cyclophosphamide or methotrexate;
immunosuppressive medicines, used to prevent rejection after organ or bone marrow transplantation, such as cyclosporine;
cardiac glycosides (e.g., digoxin, medicines used to strengthen the heart);
laxatives, medicines used to facilitate defecation;
barbiturates, drugs acting as central nervous system depressants leading to sedation;
opioid analgesics, strong painkillers without anti-inflammatory effects;
carbenoxolone, a medicine used to treat intestinal tract inflammation;
medicines usually used to prevent rejection of transplanted organs (sirolimus, everolimus, and other mTOR inhibitors). See section "Warnings and precautions".

Your doctor may consider it necessary to adjust your dose and/or take other precautions:
If you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "Do not take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG" and "Warnings and precautions").

ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG and alcohol
Drinking alcohol while taking this medicine may enhance the blood pressure-lowering effect (and may therefore cause, among other things, dizziness upon standing).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
If you think you are pregnant or could be pregnant, inform your doctor. Your doctor will usually advise you to stop treatment with ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG before conception or as soon as pregnancy is confirmed, and will recommend an alternative medicine.
ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG is not recommended during pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the fetus if taken beyond the third month.

Breastfeeding
Inform your doctor if you are breastfeeding or plan to start breastfeeding. ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG is not recommended for breastfeeding mothers.

Driving and using machines
Some patients taking this medicine have reported dizziness and fatigue. If you experience either of these symptoms, avoid driving or operating machinery (see also section "4. Possible side effects").

ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Enalapril Hydrochlorothiazide Hexal AG

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is:
Adults
The usual dose is one tablet once daily.
Renal impairment
Your doctor will carefully adjust the dose of enalapril and hydrochlorothiazide.
If you are being treated with diuretics
Previous treatment with diuretics should be discontinued 2–3 days before starting therapy with this medicine.
Method of administration
The tablets should be swallowed with a glass of water.
This medicine can be taken with or without food.
The break line is only intended to help you split the tablet if you have difficulty swallowing it whole.
If you take more ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG than you should
If you (or someone else) have taken an excessive number of tablets, or if you suspect that a child has swallowed one or more tablets, seek immediate medical help. An overdose may cause low blood pressure, excessive increase or decrease in heart rate, palpitations (the sensation of abnormally rapid or irregular heartbeat), shock, labored breathing, cough, feeling unwell, cramps, dizziness, drowsiness and confusion or anxiety, excessive urination (passing urine) or inability to urinate. Show this patient information leaflet, any remaining tablets, and the medicine packaging to the hospital staff or doctor so they can identify which tablets have been taken.
If you forget to take ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
Do not take a double dose to make up for the missed tablet; simply take the next dose at your usual time.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.
If you stop taking ENALAPRIL HYDROCHLOROTHIAZIDE HEXAL AG
Treatment for high blood pressure is long-term therapy, and stopping treatment should be discussed with your doctor. Stopping or interrupting treatment may cause an increase in blood pressure.
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.
If you experience any of the following side effects, stop taking this medicine and
contact your doctor immediately or go to the nearest hospital emergency department:

a severe allergic reaction called angioedema (skin rash, itching, swelling of the extremities, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing). This is a serious and common side effect. You may require urgent medical treatment or hospitalisation;
jaundice (yellowing of the skin and whites of the eyes). This is a potentially serious but rare side effect, indicating liver problems (liver inflammation, liver failure, which may be fatal). You may require urgent medical treatment or hospitalisation;
sudden onset of myopia. The frequency of this side effect is unknown (cannot be estimated from the available data).
Decreased vision or eye pain with redness due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma). If you suddenly develop a painful red eye, contact your doctor immediately; treatment may be required to prevent permanent vision loss. The frequency of this side effect is unknown (cannot be estimated from the available data). This medicine commonly causes a reduction in blood pressure, which may be associated with a sensation of light-headedness and weakness. In some patients, these symptoms may occur after the first dose or with any dose increase. If you experience these symptoms, contact your doctor immediately.

This medicine may cause a reduction in the number of white blood cells in the blood, which may lower your resistance to infections. If you develop an infection with symptoms such as fever and severe deterioration in your general condition, or fever with signs of local infection such as sore throat/pharyngitis/mouth inflammation, or urinary symptoms, contact your doctor immediately. A blood test will be performed to check for a possible reduction in white blood cells (agranulocytosis). It is important that you inform your doctor that you are taking this medicine.

This medicine rarely causes severe allergic reactions with high fever, skin rash with circular skin lesions (erythema multiforme), Stevens-Johnson syndrome and toxic epidermal necrolysis (serious skin conditions with redness, peeling and blistering of the skin). If these symptoms occur, you must contact your doctor immediately.

Very commonly, cough has been reported with the use of this medicine and other ACE inhibitors. This cough may persist for a long time and may also be a symptom of another upper respiratory tract disorder. If you develop this symptom, contact your doctor.

The following side effects have also been reported:

Very common: may affect more than 1 in 10 people

blurred vision
dizziness
nausea
weakness
cough

Common: may affect up to 1 in 10 people

headache, depression
low levels of potassium in the blood, which may cause muscle weakness, cramps or irregular heartbeat
high levels of cholesterol or fats in the blood, high levels of uric acid in the blood
fainting, angina or chest pain, changes in heart rhythm, excessively fast heartbeat (tachycardia)
shortness of breath
diarrhoea, abdominal pain, altered taste
skin rash
fatigue
high levels of potassium in the blood, which may cause heart rhythm abnormalities
increased levels of creatinine in the blood
low blood pressure, even associated with changes in posture (e.g. a sensation of light-headedness or weakness when standing up from a lying position)

Uncommon: may affect up to 1 in 100 people

reduction in the number of red blood cells in the blood, which may cause paleness, weakness or difficulty breathing (anaemia)
heart attack or stroke (“mini-stroke”), probably due to excessively low blood pressure in high-risk patients (patients with impaired blood flow to the heart and/or brain)
low levels of magnesium in the blood
hypoglycaemia (low blood sugar levels – see “Warnings and precautions” in section 2)
confusion, drowsiness, insomnia, nervousness, tingling or numbness, vertigo
palpitations (awareness of a fast, strong or irregular heartbeat)
runny nose, sore throat, hoarseness, breathing difficulties, dyspnoea
intestinal obstruction, inflammation of the pancreas causing severe pain in the abdomen and back (pancreatitis), vomiting, indigestion, constipation, loss of appetite, stomach irritation, dry mouth, peptic ulcer
sweating, itching, urticaria, hair loss
kidney problems, including kidney failure, presence of protein in the urine
impotence
hot flushes, tinnitus, malaise, fever
muscle cramps
low levels of sodium in the blood, which may cause fatigue and confusion, muscle cramps, seizures or coma, dehydration and low blood pressure, which in turn may cause dizziness when standing up
increased levels of urea in the blood

Rare: may affect up to 1 in 1,000 people

reduction in the number of white blood cells, making infections more likely, reduction in the count of other blood cells including platelets, changes in blood composition, poor bone marrow production, swollen glands in the neck, armpits or groin, autoimmune disease, in which the body attacks itself
strange dreams, sleep disorders
muscle weakness, sometimes due to low potassium (paresis)
Raynaud's syndrome, a blood vessel disorder which may cause tingling in the fingers and toes, which subsequently turn pale, then bluish and then red
lung disorders, including pneumonia, inflammation of the nasal mucosa causing a runny nose (rhinitis)
mouth ulcers, inflammation of the tongue
liver disorders, inflammation of the gallbladder
severe skin rashes with skin and hair loss (exfoliative dermatitis), cutaneous lupus erythematosus (an autoimmune disease), red skin rash with skin peeling (erythroderma), small fluid-filled blisters on the skin (pemphigus), purple or red spots on the skin (purpura)
reduced urine output
inflammation of the kidneys (interstitial nephritis)
breast enlargement in men
increased levels of liver enzymes and waste substances produced by the liver
increased blood sugar levels

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

intestinal swelling
high levels of calcium in the blood (see “Other medicines and ENALAPRIL IDROCLOROTIAZIDE HEXAL AG” in section 2)

Not known: frequency cannot be estimated from the available data

inappropriate secretion of antidiuretic hormone (known as SIADH), causing among others the following general symptoms: confusion, nausea, mood changes, seizures and loss of consciousness
a complex side effect has been reported which may include some or all of the following signs: fever, severe inflammation, inflammation of blood vessels, muscle pain and/or joint pain, changes in blood composition and increased erythrocyte sedimentation rate (a test to detect inflammation), rash, photosensitivity and other skin effects
skin and lip cancer (non-melanoma skin cancer)

Other side effects observed with hydrochlorothiazide doses higher than 6 mg (12.5 mg or 25 mg)

Muscle cramps (common)
Uric acid crystals in the joints (gout) (uncommon)
Decreased sexual desire (uncommon)
Flatulence (uncommon)
Joint pain (uncommon)

Reporting of suspected adverse reactions

If you experience any side effect, 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 http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enalapril Hydrochlorothiazide Hexal AG

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 and outer packaging after EXP.. The expiry date refers to the last day of that month.
Do not store above 30°C. Store in the original packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What ENALAPRIL IDROCLOROTIAZIDE HEXAL AG contains
The active substances are enalapril maleate and hydrochlorothiazide.
Each tablet contains 20 mg of enalapril maleate and 6 mg of hydrochlorothiazide.
The other components are: monohydrate lactose, magnesium stearate, maize starch, sodium hydrogen carbonate, and talc.

Description of the appearance of ENALAPRIL IDROCLOROTIAZIDE HEXAL AG and contents of the pack
ENALAPRIL IDROCLOROTIAZIDE HEXAL AG is presented as white, oval, biconvex tablets, with a break line on one side and the marking “EN20” on the other side.
The tablets are packaged in aluminum/aluminum blisters and placed in a carton box.
ENALAPRIL IDROCLOROTIAZIDE HEXAL AG is available in packs containing 14, 20, 28, 30, 49, 49x1, 50, 50x1, 98, 100, and 100x1 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder
HEXAL AG – Industriestrasse, 25 – 83607 Holzkirchen (Germany)
Representative in Italy:
Sandoz Spa – Largo U. Boccioni, 1 – 21040 Origgio (VA)

Manufacturer:

Salutas Pharma GmbH - Otto von Guericke Allee 1 - 39179 Barleben (Germany)
HEXAL A/S - Kanalholmen 8-12 - 2650 Hvidovre (Denmark)

This medicinal product has been authorized in the EEA Member States under the following names:
Austria: Enac plus Hexal 20 mg/6 mg - Tabletten
Denmark: Enahexal comp 20 mg/6 mg
Germany: EnaHEXAL comp 20 mg/6 mg Tabletten
Italy: ENALAPRIL IDROCLOROTIAZIDE HEXAL AG
Netherlands: Enalaprilmaleaat/Hydrochloorthiazide Sandoz 20/6, tabletten 20/6 mg
Sweden: Linatil comp mite 20 mg/6 mg Tablett