Enalapril/hydrochlorothiazide Combix 20/12.5 mg tablets EFG

Patient Information Leaflet

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Enalapril/Hydrochlorothiazide Combix 20/12.5 mg tablets EFG

Read the entire leaflet carefully before starting to take this medicine. 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 personally and you must not give it to others. It could harm them, even if their symptoms are the same as yours. If you consider any of the side effects you experience to be severe, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

In this leaflet:

1. What Enalapril/Hydrochlorothiazide Combix is and what it is used for.
2. Before taking Enalapril/Hydrochlorothiazide Combix.
3. How to take Enalapril/Hydrochlorothiazide Combix.
4. Possible side effects.
5. Storage of Enalapril/Hydrochlorothiazide Combix.
6. Further information.

1. What Enalapril/Hydrochlorothiazide Combix is and what it is used for

Enalapril/Hydrochlorothiazide Combix is a medicine containing two active substances: enalapril and hydrochlorothiazide.

Enalapril belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (ACE inhibitors). It works by dilating blood vessels, thereby lowering blood pressure.

Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics (medicines that increase urine output).

Together, enalapril and hydrochlorothiazide help reduce high blood pressure.

Your doctor has prescribed enalapril/hydrochlorothiazide to treat hypertension (high blood pressure) because it is not adequately controlled with enalapril or another ACE inhibitor alone.

2. Before taking Enalapril/Hydrochlorothiazide Combix

Do not take Enalapril/Hydrochlorothiazide Combix:

• If you are allergic (hypersensitive) to enalapril, hydrochlorothiazide, or any of the other components of this medicine.
• If you are allergic to sulfonamide-derived medicines. Ask your doctor if you are unsure what sulfonamide-derived medicines are.
• If you have previously been treated with a medicine from the same drug class as enalapril/hydrochlorothiazide (ACE inhibitors) and experienced allergic reactions with swelling of the face, lips, tongue, and/or throat, accompanied by difficulty swallowing or breathing (angioedema).
• If you have had such allergic reactions without a known cause, or if you have been diagnosed with hereditary or idiopathic angioedema (an immune system disorder causing swelling in the face and airways, and abdominal cramps).
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as the risk of angioedema (rapid swelling beneath the skin, such as in the throat) is high.
• If you have severe kidney disease. If you have anuria (you do not urinate).
• If you have severe liver disease.
• If you have diabetes or renal impairment and are being treated with a blood pressure-lowering medicine containing aliskiren.
• If you are more than 3 months pregnant (second and third trimesters of pregnancy) or breastfeeding (see sections “Pregnancy” and “Breastfeeding”). (It is also advisable to avoid enalapril/hydrochlorothiazide early in pregnancy – see Pregnancy section).
• If you have had skin cancer or develop an unexpected skin lesion 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.

If you are unsure whether you should start taking enalapril/hydrochlorothiazide, consult your doctor.

Take special care with Enalapril/Hydrochlorothiazide Combix:

In the following situations, your doctor may need to adjust your dose of enalapril/hydrochlorothiazida or monitor your blood potassium levels:

• If you have heart disease involving narrowing of the heart valves (mitral or aortic stenosis) or other factors reducing blood flow from the left chamber of the heart (obstructive hypertrophic cardiomyopathy).
• If you have conditions that reduce fluid volume or sodium levels in the body (e.g., severe vomiting, diarrhea, or if you are on high-dose diuretic therapy).
• If you have blood disorders.
• If you have diabetes and are taking antidiabetic medicines, including insulin, as dosage adjustments of your diabetes treatment may be necessary. Diabetes may cause high blood potassium levels, which can be serious.
• If you have liver problems.
• If you have kidney problems (including kidney transplant), as these may lead to high blood potassium levels, which can be serious.
• If you are undergoing dialysis.
• If you are on a salt-free diet, taking potassium supplements, potassium-sparing medicines (medicines that increase potassium levels), or salt substitutes containing potassium.
• If you develop an allergic reaction during treatment with swelling of the face, lips, tongue, and/or throat, difficulty swallowing or breathing, or dizziness; in this case, stop treatment immediately and consult your doctor. Note that black patients are more susceptible to this type of reaction to ACE inhibitors.
• If you are taking any of the following medicines, your risk of angioedema (rapid swelling beneath the skin, such as in the throat) may increase:
  • 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 about to undergo LDL apheresis treatment or desensitization therapy to reduce the effects of an allergy to bee or wasp stings.
• If you have low blood pressure (you may experience fainting or dizziness, especially with initial doses and when standing up. In such cases, lying down may help).
• If you are taking any of the following medicines for high blood pressure (hypertension):
  • An angiotensin II receptor antagonist (ARA) (also known as "sartans" – e.g., valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
  • Aliskiren.
• If you experience vision changes or eye pain, which could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, occurring within hours to a week after taking enalapril/hydrochlorothiazide.
• If you have previously experienced respiratory or lung problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide.
• If you develop severe shortness of breath or difficulty breathing after taking enalapril/hydrochlorothiazide, seek medical attention immediately.

Your doctor may regularly monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium).

See also the information under the heading “Do not take Enalapril/Hydrochlorothiazide Combix”.

• Before undergoing surgery or anesthesia (including at the dentist), inform the doctor or dentist that you are taking this medicine, as a sudden drop in blood pressure may occur in association with anesthesia.

Consult your doctor, even if any of the above circumstances have occurred to you in the past.

Inform your doctor if you think you are pregnant (or could be). Enalapril/hydrochlorothiazide 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 this stage (see Pregnancy section).

Use of other medicines:

Inform your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription, homeopathic remedies, herbal medicines, and other health-related products, as your doctor may need to adjust your dose and/or take other precautions, or it may be necessary to discontinue one of the treatments.

It is especially important to inform your doctor if you are using or have recently used any of the following medicines:

• An angiotensin II receptor antagonist (ARA) or aliskiren (see also information under the headings “Do not take Enalapril/Hydrochlorothiazide Combix” and “Take special care with Enalapril/Hydrochlorothiazide Combix”).
• Other antihypertensive medicines (lower high blood pressure), e.g., vasodilators, beta-blockers, diuretics.
• Potassium supplements (including salt substitutes).
• Potassium-sparing diuretics and other medicines that may increase blood potassium levels (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots).
• Medicines used to treat certain mental disorders such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics.
• Opioids (medicines used to treat severe pain).
• Medicines used to treat diabetes such as insulin or oral antidiabetics (e.g., metformin).
• Medicines used to treat pain or certain inflammations, such as non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid, and selective cyclooxygenase-2 (COX-2) inhibitors.
• Sympathomimetic medicines (used in treating certain heart and blood vessel disorders and some cold remedies).
• Pressor amines, such as noradrenaline.
• Muscle relaxants such as tubocurarine.
• Thrombolytic medicines (prevent blood clot formation).
• Calcium salts and vitamin D.
• Ion-exchange resins (used to lower blood cholesterol), such as cholestyramine and colestipol.
• Antiarrhythmics (used to prevent and control heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medicines (reduce gastric emptying rate), such as atropine (used before general anesthesia or to prevent spasms) or biperiden (used in patients with Parkinson’s disease).
• Medicines for gout treatment, such as probenecid, sulfinpyrazone, and allopurinol.
• Antivirals (for treating viral infections), such as amantadine.
• Cytotoxic medicines (used in cancer treatment), such as cyclophosphamide and methotrexate.
• Immunosuppressants (used to prevent organ transplant rejection), such as cyclosporine.
• Antibiotics (for treating certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases such as rheumatoid arthritis).

Taking Enalapril/Hydrochlorothiazide Combix with food and drinks:

Enalapril/hydrochlorothiazide may be taken before or after meals.

Alcohol may enhance the blood pressure-lowering (hypotensive) effect of this medicine.

Pregnancy and Breastfeeding:

Consult your doctor or pharmacist before using any medicine.

Pregnancy

Inform your doctor if you think you are pregnant (or could be). Your doctor will usually advise you to stop taking enalapril/hydrochlorothiazide before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Enalapril/hydrochlorothiazide is not recommended in early pregnancy and must not be taken after 3 months of pregnancy, as it may cause serious harm to your baby if used from the third month of pregnancy onward.

Breastfeeding

Inform your doctor if you are breastfeeding or planning to breastfeed. While taking enalapril/hydrochlorothiazide, breastfeeding is not recommended for newborns (first weeks after birth), especially premature infants. For older infants, your doctor should advise you on the benefits and risks of taking enalapril/hydrochlorothiazide compared to other treatments during breastfeeding.

Use in children and adolescents:

The safety and efficacy of enalapril/hydrochlorothiazide have not been established in this population group, and therefore its use is not recommended in children.

Use in elderly patients:

In studies combining enalapril and hydrochlorothiazide, the effects and tolerability of the medicines were similar in younger and older adult patients with high blood pressure.

Use in athletes:

Athletes are advised that this medicine contains a component that may lead to a positive result in doping control tests.

Driving and use of machines: At the beginning of treatment, symptoms such as fatigue, drowsiness, or dizziness may occur. Therefore, avoid tasks requiring special attention, such as driving or operating dangerous machinery, until your response to the medicine is satisfactory.

Important information about some of the components of Enalapril/Hydrochlorothiazide Combix:

This medicine contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Interference with diagnostic tests:

If you are scheduled for any diagnostic test to assess parathyroid gland function, inform your doctor that you are being treated with enalapril/hydrochlorothiazide, as it may alter test results.

3. How to take Enalapril/Hydrochlorothiazide Combix

Follow these instructions unless your doctor has given you different ones.

Remember to take your medicine.

Your doctor will decide the appropriate dose depending on your condition and whether you are taking other medicines.

Take enalapril/hydrochlorothiazide every day, exactly as directed by your doctor. It is very important to keep taking this medicine for the length of time recommended by your doctor. Do not take more tablets than the prescribed dose.

The usual dose is one tablet once daily. If necessary, your doctor may increase the dose to two tablets taken once daily.

The initial dose may cause a greater drop in blood pressure than occurs during continued treatment. You may feel faint or dizzy, and lying down may help. If you are concerned, consult your doctor.

Patients with impaired renal function:

If you have any kidney disease, your doctor will determine the most appropriate dose for you.

Method of administration

This medicine is administered orally.

Take the enalapril/hydrochlorothiazide tablets with a glass of water.

Enalapril/hydrochlorothiazide may be taken before or after meals.

If you take more Enalapril/Hydrochlorothiazide Combix than you should:

If you have taken more enalapril/hydrochlorothiazide than you should, contact your doctor or pharmacist immediately, or contact the Poison Information Service, Telephone: 91-562 04 20, stating the medicine and the amount taken.

It is recommended to bring the medicine package and leaflet to healthcare personnel.

The most likely symptoms in case of overdose are: dizziness or vertigo due to a sudden or excessive drop in blood pressure, and/or excessive thirst, disorientation, decreased urine output, and/or tachycardia.

If you forget to take Enalapril/Hydrochlorothiazide Combix:

You should take enalapril/hydrochlorothiazide exactly as directed by your doctor. Do not take a double dose to make up for a missed dose. Simply take the next dose as usual.

If you stop treatment with Enalapril/Hydrochlorothiazide Combix:

Your doctor will advise you on how long your treatment with enalapril/hydrochlorothiazide should last. Do not stop treatment early, even if you feel better.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

The adverse effects reported are listed below according to the following frequencies:

Very common: (occur in at least 1 in every 10 treated patients)

Common: (occur in at least 1 in every 100 and less than 1 in 10 treated patients)

Uncommon: (occur in at least 1 in every 1,000 and less than 1 in 100 treated patients)

Rare: (occur in at least 1 in every 10,000 and less than 1 in 1,000 treated patients)

Very rare: (occur in less than 1 in 10,000 treated patients)

Frequency not known: (cannot be estimated from available data)

Disorders of the blood and lymphatic system:

Uncommon: decrease in red blood cells (blood cells that carry oxygen)

Rare: reduction in a type of white blood cells (neutrophils), decrease in hemoglobin (the oxygen-carrying protein in red blood cells), decrease in the number of platelets in blood, decrease in hematocrit (proportion of red blood cells in blood), decrease in the number of white blood cells, bone marrow depression (reduced ability of the body to produce blood cells), lymph node inflammation, immune system disorders.

Endocrine disorders:

Frequency not known: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolism and nutrition disorders:

Common: elevated potassium levels in blood, increased cholesterol, increased triglycerides, increased blood uric acid

Uncommon: low blood glucose and magnesium levels, gout

Rare: increased blood glucose

Very rare: elevated calcium levels in blood

Nervous system disorders:

Common: headache, syncope, taste disturbance

Uncommon: confusion, drowsiness, insomnia, tingling sensation, dizziness

Rare: paralysis (due to low potassium levels)

Psychiatric disorders:

Common: depression

Uncommon: nervousness, decreased libido

Rare: abnormal dreams, sleep disorders

Eye disorders:

Very common: blurred vision

Frequency not known: decreased vision or eye pain due to increased pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma].

Ear and labyrinth disorders:

Uncommon: tinnitus (ringing in the ears)

Cardiac and vascular disorders:

Very common: dizziness

Common: drop in blood pressure associated with fainting, heart rhythm disorders, angina pectoris, tachycardia (rapid heartbeat)

Uncommon: flushing, palpitations (rapid or irregular heartbeat sensation), myocardial infarction or stroke, possibly secondary to excessive reduction in blood pressure in high-risk patients (see section "Take special care with Enalapril/Hydrochlorothiazide Combix")

Rare: changes in skin color of fingers, toes, nose, or ears (Raynaud's phenomenon)

Respiratory, thoracic and mediastinal disorders:

Very common: cough

Common: difficulty breathing

Uncommon: mucus secretion, sore throat and hoarseness, bronchospasm (difficulty breathing) and asthma

Rare: pulmonary infiltrates, respiratory discomfort (including pneumonia and pulmonary edema), nasal mucosa inflammation, allergic alveolitis (inflammation of the lung alveoli due to allergy)/eosinophilic pneumonia (a condition in which a type of white blood cells called eosinophils accumulate in the lungs)

Very rare: acute breathing difficulty (symptoms include severe shortness of breath, fever, weakness, and confusion)

Gastrointestinal disorders:

Very common: nausea

Common: diarrhea, abdominal pain

Uncommon: intestinal obstruction with severe pain, pancreatitis (inflammation of the pancreas), vomiting, digestive discomfort, constipation, loss of appetite, gastric irritation, dry mouth, peptic ulcer, flatulence (gas)

Rare: infection or inflammation of the mucous membrane of the mouth, inflammation of the tongue

Very rare: intestinal angioedema (inflammation of the intestinal wall)

Hepatobiliary disorders:

Rare: liver failure, hepatic necrosis (which may be fatal), liver inflammation, suppression or cessation of bile secretion, yellowing of the skin or eyes (jaundice), gallbladder inflammation (particularly in patients with pre-existing gallstones in the bile ducts)

Skin and subcutaneous tissue disorders:

Common: skin rash (exanthema)

Hypersensitivity/angioneurotic edema: swelling of the face, extremities, lips, tongue, glottis and/or larynx

Uncommon: excessive sweating, itching, urticaria (hives), hair loss

Rare: skin redness, severe blistering or bleeding in the skin (Stevens-Johnson syndrome), severe skin redness/rash with skin and hair loss, skin peeling, appearance of red spots on the skin, skin disorders, skin redness, blister formation on the skin, Stevens-Johnson syndrome

Frequency not known: Skin and lip cancer (non-melanoma skin cancer)

A symptomatic complex has been observed that may include some of the following reactions: fever, serositis, vasculitis, muscle inflammation/pain, joint inflammation/pain, positive antinuclear antibody test, increased erythrocyte sedimentation rate, eosinophilia, and leukocytosis. Skin rash, photosensitivity, or other skin manifestations may also occur.

Musculoskeletal, connective tissue and bone disorders:

Common: muscle cramps

Uncommon: joint pain

Renal and urinary disorders:

Uncommon: renal dysfunction (impaired kidney function), renal failure, presence of protein in urine

Rare: inadequate urine output, inflammation of kidney cells

Reproductive system and breast disorders:

Uncommon: impotence

Rare: enlargement of the breasts in men

General disorders and administration site conditions:

Very common: fatigue

Common: tiredness, chest pain

Uncommon: malaise, fever

Additional investigations:

Common: elevated potassium levels in blood, increased serum creatinine

Uncommon: increased blood urea, low sodium levels in blood

Rare: increased liver enzymes, increased serum bilirubin

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Enalapril/Hydrochlorothiazide Combix

Do not store above 25°C.

Keep in the original container.

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

Expiry: Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. Ask your pharmacist how to properly dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Enalapril/Hydrochlorothiazide Combix:

The active substances are enalapril in the form of maleate and hydrochlorothiazide.

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

The other components (excipients) are: monohydrate lactose, sodium hydrogen carbonate, corn starch, pregelatinized corn starch, magnesium stearate, and yellow iron oxide (E-172).

Appearance of the product and contents of the pack:

It is presented as tablets. The tablets are round, yellow in colour, and scored on one side. Each pack contains 28 or 30 tablets; the hospital pack contains 500 tablets.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder:

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturers:

INDUSTRIA QUÍMICA Y FARMACÉUTICA VIR, S.A.

C/. Laguna 66-68-70, 28923 ALCORCÓN (Madrid) Spain

MEDICINAL PRODUCT SUBJECT TO MEDICAL PRESCRIPTION

This leaflet was approved in: January 2022

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.es