Enalapril + Hydrochlorothiazide 20mg/12.5mg Tablets – patient leaflet, side effects, dosage

1. What Enalapril + Hydrochlorothiazide is and what it is used for

Enalapril + Hydrochlorothiazide tablets contain a combination of enalapril maleate and hydrochlorothiazide.

Enalapril belongs to a group of medicines called angiotensin converting enzyme inhibitors (ACE inhibitors), which work by widening your blood vessels.

Hydrochlorothiazide belongs to a group of medicines known as water tablets (diuretics), which increase the volume of urine you produce.

The effect of these medicines is to lower your blood pressure. Enalapril + Hydrochlorothiazide is used to treat high blood pressure (hypertension). Taking both medicines that Enalapril + Hydrochlorothiazide contains can increase their effect compared to taking just one.

This fixed dose combination is not suitable for initial therapy.

2. What you need to know before you take Enalapril + Hydrochlorothiazide

Do not take Enalapril + Hydrochlorothiazide

• if you are allergic to enalapril, hydrochlorothiazide or any of the other ingredients of this medicine (see Section 6 “Contents of the pack and other information”)
• if you are allergic to other ACE inhibitors e.g. ramipril or to sulfonamide-derived medicines (mostly antibiotics e.g. sulfamethoxazole)
• if you or your family have previously suffered from swelling of the extremities, face, lips, throat, mouth or tongue (angioedema)
• if you have severe kidney problems
• if you are not passing urine (anuria)
• if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren
• if you have a condition known as renal artery stenosis (narrowing of the arteries
• that supply the blood to your kidneys)
• if you have severe liver problems or a neurological disorder as a result of severe liver problems (hepatic encephalopathy)
• if you are more than 3 months pregnant. (It is also better to avoid Enalapril + Hydrochlorothiazide in early pregnancy (see “pregnancy” section)
• if you are taking sacubitril/valsartan, a medicine used to treat heart failure

Warnings and precautions

Talk to your doctor before taking this medicine:

• if you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase of pressure in your eye and can happen within hours to a week of taking Enalapril + Hydrochlorothiazide. This can lead to permanent vision loss, if not treated. If you earlier have had a penicillin or sulfonamide allergy, you can be at higher risk of developing this
• if you have had skin cancer or if you develop an unexpected skin lesion during the treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of some types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Enalapril + Hydrochlorothiazide
• if you have narrowing of the arteries (atherosclerosis), cerebrovascular problems such as a stroke or transient ischaemic attack (TIA, a "mini-stroke")
• if you have heart failure
• if you have low blood pressure, are on a salt restricted diet or have recently suffered from excessive vomiting and/or diarrhoea
• if you have abnormal levels of water and minerals in your body (fluid/electrolyte imbalance)
• if you have heart muscle disease (hypertrophic cardiomyopathy), a narrowing of the main artery carrying blood away from the heart, the aorta (aortic stenosis), or other forms of a heart problem called outflow obstruction
• if you have diabetes and are taking antidiabetic medicines, including insulin to
• control your diabetes (you should monitor your blood for low blood glucose levels, especially during the first month of treatment)
• if you suffer from gout, have high levels of uric acid in your blood
• if you are taking allopurinol, (used for the treatment of gout), or procainamide, (used to treat abnormal heart rhythms). If you develop an infection, you should let your doctor know immediately. Your doctor may take a blood sample from time to time to check your white blood cell count
• if you have kidney problems, have had a recent kidney transplantation, are a dialysis patient, only have one functioning kidney or are taking water tablets (diuretics)
• if you have blood disorders or liver problems
• if you are taking potassium supplements or potassium containing salt substitutes
• if you are taking other medicines that can affect the level of potassium in your blood, such as heparin (an anticoagulant)
• if you have high levels of potassium in the blood
• if you have collagen vascular disease such as systemic lupus erythematosus (SLE) or scleroderma, which may be associated with skin rashes, joint pain and fever
• if you are taking immunosuppressant therapy (used for the treatment of autoimmune disorders such as rheumatoid arthritis or following transplant surgery)
• if you are taking lithium, used for the treatment of some psychiatric illnesses (see “Other medicines and Enalapril + Hydrochlorothiazide” section)
• if you suffer from allergies or asthma
• if you think you are (or might become) pregnant. This medicine is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).

• if you are taking any of the following medicines used to treat high blood pressure:

  • an angiotensin II receptor blocker (ARBs) (also known as sartans - for example valsartan, telmisartan, irbesartan), in particular if you have diabetes-related kidney problems.
  • Aliskiren

• If you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin in area such as the throat) is increased:

  • sirolimus, everolimus and other medicines belonging to the class of mTOR inhibitors (used to avoid rejection of transplanted organs)

If you are about to have any of the following procedures, you should tell your doctor who is treating you that you are taking Enalapril + Hydrochlorothiazide:

• any surgery or receive anaesthetics (even at the dentist)
• a treatment called LDL apheresis, to remove cholesterol from your blood using a machine
• desensitisation treatment, to reduce the effect of an allergy to bee or wasp stings.

Routine tests

When you first start to take Enalapril + Hydrochlorothiazide, your doctor will monitor your blood pressure frequently to ensure you have been given the correct dose. In addition, for some patients the doctor may want to do some tests to measure your potassium, sodium, magnesium, creatinine and liver enzyme levels.

Tell your doctor if you have or will take an anti-doping test, as Enalapril + Hydrochlorothiazide contains an active ingredient that can produce a positive result.

Children

This medicine is not recommended for use in children.

Other medicines and Enalapril + Hydrochlorothiazide

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. This includes herbal medicines.

This applies in particular if you are also taking:

• Medicines which are most often used to avoid rejection of transplanted organs (temsirolimus, sirolimus, everolimus and other medicines belonging to the class of mTOR inhibitors). See section “Warnings and precautions”.
• Potassium supplements or salt substitutes containing potassium, diuretics (water tablets, in particular potassium-sparing), other drugs which can increase potassium in your body (such as heparin and co-trimoxazole also known as trimethoprim/sulfamethoxazole).

Medicines which may interact with or be affected by Enalapril + Hydrochlorothiazide:

• potassium-sparing water tablets (diuretics) such as spironolactone, eplerenone, triamterene or amiloride (see above)
• medicines used to increase frequency of urination (diuretics), including kaliuretic diuretics such as furosemide
• medicines used to treat angina and heart failure, such as nitroglycerine, nitrates and vasodilators (medicines used to widen the blood vessels)
• narcotic pain relievers such as morphine (opioid analgesics)
• tricyclic antidepressants, used to treat depression
• lithium, a medicine used to treat mood disorders (antipsychotic)
• non-steroidal anti-Inflammatory drugs (NSAIDs), medicines used to treat certain rheumatic disorders
• gold injection (sodium aurothiomalate), a medicine used to treat rheumatic arthritis
• medicines used to treat severe allergic reactions such as noradrenaline and ephedrine, used in some cough and cold remedies (sympathomimetics)
• medicines used to treat diabetes, such as insulin
• medicines used to treat anxiety or sleep disorders (barbiturates)
• medicines used to lower cholesterol such as cholestyramine or colestipol
• corticosteroids, medicines used to reduce inflammation
• ACTH, used to test whether your adrenal glands are working properly
• muscle relaxants such as tubocurarine
• medicines used to treat gout such as allopurinol, probenecide, sulfinpyrazone
• medicines used to treat cancer, such as cyclophosphamide or methotrexate
• medicines used to treat irregular heartbeats such as digoxin (cardiac glycosides)
• medicines used to treat irregular heart rhythms such as quinidine, procainamide, amiodarone, sotalol
• laxatives, medicines used to treat constipation
• carbenoxolone, used to treat oral ulcers
• a medicine containing a neprilysin inhibitor such as sacubitril (available as fixed-dose combination with valsartan) and racecadotril. See “Do not take Enalapril + Hydrochlorothiazide”.

Your doctor may need to change your dose and/or to take other precautions:

• If you are taking an angiotensin II receptor blocker (ARB) or aliskiren (see also information under the headings “Do not take Enalapril + Hydrochlorothiazide” and “Warnings and precautions”)

Taking Enalapril + Hydrochlorothiazide with food, drink and alcohol

• These tablets can be taken with or without food.

• Drinking alcohol together with this medicine may increase the blood pressure-lowering

  effect and may cause dizziness, light-headedness or fainting.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

• Your doctor will normally advise you to stop taking Enalapril + Hydrochlorothiazide before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Enalapril + Hydrochlorothiazide.
• Enalapril + Hydrochlorothiazide is not recommended during pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

• Enalapril + Hydrochlorothiazide is not recommended for mothers who are breast-feeding.
• Both enalapril and hydrochlorothiazide are excreted into breast milk.
• Hydrochlorothiazide can also reduce the amount of milk and cause other side effects.

Driving and using machines

Dizziness or weariness may occur. If you experience either of these symptoms, it may be necessary to avoid driving or operating machinery.

Enalapril + Hydrochlorothiazide contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Enalapril + Hydrochlorothiazide

Always take Enalapril + Hydrochlorothiazide exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

• The tablets can be taken with or without food.
• The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

The recommended dose is:

Adults

The usual dose is one tablet taken once a day. Your doctor may increase the dose to two tablets each day.

Older people

Your doctor may adjust the dose of Enalapril + Hydrochlorothiazide carefully.

Patients with kidney problems

Your doctor will adjust the dose of Enalapril + Hydrochlorothiazide carefully.

Use in children

Enalapril + Hydrochlorothiazide is not recommended for use in children.

If you take more Enalapril + Hydrochlorothiazide than you should

If you accidentally take too many tablets, contact the doctor, or nearest hospital emergency department immediately for advice. Remember to take this leaflet or any remaining tablets with you.

Symptoms of an overdose may include: shock, electrolyte imbalance, kidney failure, fast breathing (hyperventilation), faster/slower heartbeat (tachycardia, bradycardia), feeling your heartbeat (palpitations), dizziness, anxiety and cough.

If you forget to take Enalapril + Hydrochlorothiazide

Take it as soon as you remember, unless it is time for your next dose. If you miss a dose do not take a double dose to make up for a forgotten dose.,

If you stop taking Enalapril + Hydrochlorothiazide

It is important that you keep taking this medicine for as long as your doctor has told you to. Interruption or stopping your treatment could cause your blood pressure to increase.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects:

Stop taking this medicine and seek medical advice immediately if you develop the following symptoms:

• Allergic reactions: swelling of the face, throat or tongue, difficulty in breathing or dizziness
• Swelling of the arms and/or legs, lips, tongue or throat (angioneurotic oedema)
• Swelling of the intestines which may cause stomach pain, with or without being sick (intestinal angioedema) – see “Very rare side effects” section
• Jaundice (yellowing of the skin or the whites of the eyes)
• Fever, general ill feeling, itching, joint aches, multiple skin lesions (erythema multiforme)
• Severe blistering of the skin (toxic epidermal necrolysis), mouth, eyes and genitals (Stevens Johnson syndrome)
• Decrease in vision or pain in your eyes due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma)

Other side effects:

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

• Blurred vision
• Dizziness
• Cough
• Feeling sick (nausea)
• General weakness (asthenia)

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

• Abnormally low levels of potassium in blood (hypokalaemia)
• Increased levels of fats (cholesterol, triglycerides) and uric acid in the blood
• Headache
• Depression
• Fainting (syncope), tiredness (fatigue)
• Abnormal sense of taste
• Low blood pressure, sometimes causing dizziness or lightheadedness after a change in position i.e. when standing up from a lying or sitting position (hypotension, orthostatic hypotension)
• Chest pain (including angina), abnormal heart rhythm, faster heartbeat (tachycardia)
• Shortness of breath (dyspnoea)
• Diarrhoea, stomach pain
• Skin rashes (exanthema), swelling of the face, extremities, lips, tongue, and/or throat has been reported (see “Serious side effects” section)
• Muscle cramps
• Abnormally high levels of potassium in blood (hyperkalaemia)
• Kidney problems

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

• Looking pale and feeling tired (anaemia), severe reduction in blood cells which can cause weakness, bruising or make infections more likely (aplastic anaemia), reduction in red blood cells which can make the skin pale yellow and cause weakness or breathlessness (haemolytic anaemia)
• Low blood sugar levels (hypoglycaemia)
• Low level of magnesium in the blood (hypomagnesaemia)
• Pain and swelling in one or more joints (gout), joint pain (arthralgia)
• Confusion
• Sleepiness or difficulty in sleeping (insomnia)
• Nervousness
• Tingling or numbness in the hands or feet (paraesthesia)
• A sensation of whirling and loss of balance, feeling dizzy or giddy (vertigo)
• Ringing in the ears (tinnitus)
• Feeling your heartbeat (palpitations)
• Heart attack or stroke (in high risk patients)
• Difficulty breathing (bronchospasm), asthma, sore throat, hoarseness, dry mouth
• Stomach disturbances - intestinal obstruction (ileus), inflammation of the pancreas (pancreatitis), being sick (vomiting), indigestion (dyspepsia), constipation, loss of appetite, stomach irritation, peptic ulcer and wind (flatulence)
• Fever, flushing, excessive sweating (diaphoresis)
• Severe itching (pruritus), skin rashes with the formation of wheals (urticaria)
• Hair loss (alopecia)
• Kidney problems, kidney failure, protein in the urine, high blood urea
• Inability to maintain an erection (impotence)
• Generally feeling unwell (malaise)
• Abnormally low levels of salt (sodium) in blood (hyponatremia)

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

• Abnormal condition of the bone marrow in which it is unable to produce normal amounts of red and/or white blood cells and platelets leaving the immune system in a weakened state and vulnerable to infection (bone marrow depression) which may increase the risk of bleeding or bruising (thrombocytopenia) and/or make infections more likely (leucopenia, neutropenia, agranulocytosis, pancytopenia)
• Swollen/enlarged lymph nodes (lymphadenopathy)
• Illnesses that cause the immune system to attack the body (autoimmune diseases)
• Increased blood sugar levels (hyperglycaemia)
• Abnormal dreams, sleep disorders
• Partial loss of movement (due to low level of potassium)
• Poor circulation causing fingers & toes to be pale & numb (Raynaud's syndrome)
• Lung/breathing problems - inflammation of the lungs, excess collection of watery fluid in the lungs (pulmonary oedema), shortness of breath or difficulty in breathing (allergic alveolitis)
• Collective symptoms of cough, fever, difficulty breathing, and sweating at night (eosinophilic pneumonia)
• Runny nose (rhinitis)
• Mouth ulcers, inflammation of the tongue
• Liver damage and/or failure, inflammation of the liver (hepatitis)
• Inflammation of the gallbladder (cholecystitis)
• Skin conditions - peeling of the skin over large areas of the body (exfoliative dermatitis/erythroderma), skin rash caused by small blood vessels bleeding into the skin (purpura), blistering of the skin (pemphigus)
• Condition which causes joint pain, skin rashes and fever (cutaneous lupus erythematosus)
• Low output of urine (oliguria)
• Inflammation of the kidneys (interstitial nephritis)
• Excessive development of the male breast (gynaecomastia)
• Increase in the amount of enzymes and waste produced by the liver

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

• Increased level of calcium in the blood (hypercalcemia)
• Stomach pain or cramping, feeling and/or being sick (intestinal angioedema) – see “Serious side effects” section

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

• Skin and lip cancer (non-melanoma skin cancer)
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH). Anti-Diuretic Hormone (ADH) is produced by the brain and is stored in & released by the pituitary gland. ADH controls how your body releases and conserves water. SIADH occurs when ADH is produced somewhere other than the brain, which makes it difficult for your body to get rid of excess water. This causes a build-up of fluids as well as abnormally low sodium levels
• A symptom complex which may include some or all of the following: fever, inflammation of the serous tissues of the body, inflammation of the blood vessels, muscle pain/inflammation, joint pain, arthritis, a positive ANA (a test used to detect auto-immune disorders), elevated ESR (a blood test that measures how much inflammation is in the body), eosinophilia (frequent wheezing, breathlessness, abdominal pain, diarrhoea, fever, cough and rashes due to an increase in certain white blood cells). Rash. increased sensitivity of the skin to sunlight (photosensitivity) or other skin conditions may also occur

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine

5. How to store Enalapril + Hydrochlorothiazide

• Keep this medicine out of the sight and reach of children.

  Do not store above 30°C. Store in the original package in order to protect from moisture.

• Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What Enalapril + Hydrochlorothiazide contains:

Each tablet contains 20 mg of enalapril maleate and 12.5 mg of hydrochlorothiazide.

The other ingredients are: sodium hydrogen carbonate, maize starch, lactose monohydrate, calcium hydrogen phosphate dehydrate, talc, magnesium stearate.

What Enalapril + Hydrochlorothiazide looks like and contents of the pack:

Enalapril + Hydrochlorothiazide 20 mg/12.5 mg tablets are white, oval, biconvex, with a break-line on one side of the tablet and the stamp "E H" on the other side of the tablet.

Enalapril + Hydrochlorothiazide is available in:

Enalapril + Hydrochlorothiazide 20 mg/12.5 mg Tablets are available in pack of 10, 14, 20, 28, 30, 49, 50, 50x1, 60, 98 and 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation Holder:

Pharmapoint UK Ltd

30 Hatfeild Mead

Morden, Surrey

SM4 5PE

United Kingdom

Manufacturer:

Salutas Pharma GmbH

Otto-von-Guericke-Alle 1

39179 Barleben

Germany

Product Licence Number:

PL 45816/0001

This leaflet was last revised in 06/2023