ENALAPRIL/HYDROCHLOROTHIAZIDE COMBIX 20/12.5 mg TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER.

Enalapril/Hydrochlorothiazide Combix 20/12.5 mg tablets EFG

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. Storing Enalapril/Hydrochlorothiazide Combix.
6. Further information

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

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

Enalapril belongs to a group of medicines called angiotensin-converting enzyme inhibitors (ACE inhibitors). It works by widening the blood vessels, which lowers blood pressure.

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

Together, enalapril and hydrochlorothiazide help to lower high blood pressure.

Your doctor has prescribed enalapril/hydrochlorothiazide to treat high blood pressure (hypertension) because it is not adequately controlled with enalapril or an 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 ingredients of this medicine.
• If you are allergic to sulfonamide-derived medicines. Ask your doctor if you are not sure what sulfonamide-derived medicines are.
• If you have previously been treated with a medicine from the same group of medicines as enalapril/hydrochlorothiazide (ACE inhibitor) and have had allergic reactions with swelling of the face, lips, tongue, and/or throat with 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 that causes inflammation in the face and respiratory tract, and abdominal colic).
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults, as the risk of angioedema (rapid swelling under the skin in areas such as the throat) is high.
• If you have severe kidney disease. If you have anuria (do not urinate).
• If you have severe liver disease.
• If you have diabetes or kidney failure and are being treated with a blood pressure-lowering medicine that contains aliskiren.
• If you are pregnant for more than 3 months (second and third trimester of pregnancy) or are breastfeeding (see sections "Pregnancy" and "Breastfeeding"). (It is also recommended to avoid enalapril/hydrochlorothiazide at the beginning of pregnancy - see section Pregnancy).
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, in particular its long-term use at high doses, may increase the risk of certain 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 are not sure whether you should start taking enalapril/hydrochlorothiazide, consult your doctor.

Be especially careful with Enalapril/Hydrochlorothiazide Combix:

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

• If you have a heart condition that involves narrowing of the heart valves (mitral or aortic stenosis) or other factors that reduce blood flow from the left ventricle of the heart (hypertrophic obstructive cardiomyopathy).
• If you have disorders that reduce fluid volume or sodium levels in the body (e.g., severe vomiting, diarrhea, or if you are being treated with high doses of diuretics).
• If you have blood disorders.
• If you have diabetes and are taking medicines to treat diabetes, including insulin, as your doctor may need to adjust the dose of your diabetes medicines. Diabetes can cause high potassium levels in the blood, which can be serious.
• If you have liver problems.
• If you have kidney problems (including kidney transplant), as they can cause high potassium levels in the blood, which can be serious.
• If you are undergoing dialysis.
• If you follow a low-salt diet, take potassium supplements, or take potassium-sparing medicines (medicines that increase potassium levels) or salt substitutes that contain potassium.
• If you experience an allergic reaction with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing, as well as dizziness; in this case, stop treatment and consult your doctor immediately. You should be aware that black patients are more sensitive to this type of reaction to ACE inhibitors.
• If you are taking any of the following medicines, the risk of angioedema may increase (rapid swelling under the skin in areas such as the throat):
• Racecadotril (a medicine used to treat diarrhea),
• Medicines used to prevent organ transplant rejection and cancer (e.g., temsirolimus, sirolimus, everolimus), Vildagliptin, a medicine used to treat diabetes.
• If you are about to undergo a treatment called LDL apheresis, or a desensitization treatment to reduce the effect of an allergy to bee or wasp stings.
• If you have low blood pressure (you may notice dizziness or lightheadedness, especially when standing up. In these cases, lying down may help).
• If you are taking any of the following medicines used to treat high blood pressure (hypertension):
• • An angiotensin II receptor antagonist (ARA) (also known as "sartans" - e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
  • Aliskiren
• If you experience a decrease in vision or eye pain, they could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in eye pressure, and can occur within a few hours to a week after taking enalapril/hydrochlorothiazide.
• If you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking enalapril/hydrochlorothiazide, seek medical attention immediately.

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 heading "Do not take Enalapril/Hydrochlorothiazide Combix".

• Before undergoing surgery or anesthesia (even at the dentist), inform your doctor or dentist that you are taking this medicine, as there may be a sudden drop in blood pressure associated with anesthesia.

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

You must inform your doctor if you think you are pregnant (or might be). Enalapril/hydrochlorothiazide is not recommended at the beginning of pregnancy and should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if used from the third month of pregnancy onwards (see section Pregnancy).

Using other medicines:

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription, homeopathic medicines, herbal remedies, 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 stop treatment with one of them.

It is especially important that you 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 the information under the headings "Do not take Enalapril/Hydrochlorothiazide Combix" and "Be especially careful with Enalapril/Hydrochlorothiazide Combix")
• Other anti-hypertensive medicines (that lower high blood pressure), such as vasodilators, beta-blockers, diuretics.
• Potassium supplements (including salt substitutes),
• potassium-sparing diuretics and other medicines that may increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporin, 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.
• Narcotics (medicines used to treat severe pain).
• Medicines used to treat diabetes, such as insulin or oral anti-diabetics (e.g., metformin).
• Medicines used to treat pain or certain inflammations, such as non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, including selective cyclooxygenase-2 (COX-2) inhibitors.
• Sympathomimetic medicines (medicines used to treat certain heart and blood vessel disorders and some cold medicines).
• Pressor amines, such as noradrenaline.
• Muscle relaxants, such as tubocurarine.
• Thrombolytic medicines (that prevent blood clot formation).
• Calcium salts and vitamin D.
• Ion exchange resins (medicines used to lower cholesterol levels in the blood), such as cholestyramine and colestipol.
• Anti-arrhythmic medicines (used to prevent and control heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medicines (medicines that slow down gastric emptying), such as atropine (used before general anesthesia or to prevent spasms) or biperiden (used in patients with Parkinson's disease).
• Medicines used to treat gout, such as probenecid, sulfinpyrazone, and allopurinol.
• Antiviral medicines (used to treat viral infections), such as amantadine.
• Cytotoxic medicines (used to treat cancer), such as cyclophosphamide and methotrexate.
• Immunosuppressant medicines (used to prevent organ transplant rejection), such as cyclosporin.
• Antibiotics (medicines used to treat 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 can be taken before or after meals.

Alcohol may increase the blood pressure-lowering effect of this medicine.

Pregnancy and Breastfeeding:

Consult your doctor or pharmacist before using a medicine.

Pregnancy

You must inform your doctor if you think you are pregnant (or might be). Normally, your doctor will 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 a different medicine instead of enalapril/hydrochlorothiazide. Enalapril/hydrochlorothiazide is not recommended at the beginning of pregnancy and should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if used from the third month of pregnancy onwards (see section Pregnancy).

Breastfeeding

Tell your doctor if you are breastfeeding or about to start breastfeeding. While taking enalapril/hydrochlorothiazide, breastfeeding is not recommended in newborns (first few weeks after birth), and especially in premature babies. In the case of an older baby, your doctor should advise you on the benefits and risks of taking enalapril/hydrochlorothiazide, compared to other treatments, while breastfeeding.

Use in children and adolescents:

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

Use in elderly patients:

In studies where enalapril and hydrochlorothiazide were taken together, the effect of the medicines and tolerability were similar in young adult and elderly patients with high blood pressure.

Use in athletes

Athletes are informed that this medicine contains a component that may produce a positive result in doping tests.

Driving and using machines:At the beginning of treatment, symptoms of fatigue and drowsiness or a feeling of instability may occur. It is therefore advisable not to perform tasks that require special attention, such as driving and using hazardous machinery, until the response to the medicine is satisfactory.

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

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

Interference with diagnostic tests

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

3. How to take Enalapril/Hydrochlorothiazide Combix

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

Remember to take your medicine.

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

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

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

The initial dose may cause a greater drop in blood pressure than will occur after continued treatment. You may notice dizziness or lightheadedness, and lying down may help. If you are concerned, consult your doctor.

Patients with impaired renal function:

If you have kidney disease, your doctor will indicate the most suitable dose.

Method of administration

This medicine is administered orally.

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

Enalapril/hydrochlorothiazide can 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, consult your doctor or pharmacist immediately, or contact the Toxicology Information Service, Telephone: 91-562 04 20, indicating the medicine and the amount taken.

It is recommended to take the package and leaflet of the medicine to the 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 production, and/or rapid heartbeat.

If you forget to take Enalapril/Hydrochlorothiazide Combix:

You should take enalapril/hydrochlorothiazide as indicated by your doctor. Do not take a double dose to make up for forgotten doses. Just take the next dose as usual.

If you stop taking Enalapril/Hydrochlorothiazide Combix

Your doctor will indicate the duration of your treatment with enalapril/hydrochlorothiazide. Do not stop treatment before, even if you feel better.

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

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them.

The recorded adverse effects are detailed below according to the following frequencies:

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

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

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

Rare: (occur in at least 1 in 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 the available data)

Blood and lymphatic system disorders:

uncommon: decrease in red blood cells (oxygen-transporting blood cells)

rare: reduction of a type of white blood cells (neutrophils), decrease in hemoglobin (protein in red blood cells that transports oxygen), decrease in platelet count, decrease in hematocrit (proportion of red blood cells in the blood), decrease in white blood cell count, bone marrow depression (decrease in the body's ability to form blood cells), lymph node inflammation, immune system diseases.

Endocrine disorders:

unknown frequency: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolic and nutritional disorders:

frequent: high potassium levels in the blood, increased cholesterol, increased triglycerides, increased uric acid in the blood

uncommon: low glucose and magnesium levels in the blood, gout

rare: increased glucose in the blood

very rare: high calcium levels in the blood

Nervous system disorders:

frequent: headache, syncope, altered taste

uncommon: confusion, somnolence, insomnia, tingling sensation, vertigo

rare: paralysis (due to low potassium levels).

Psychiatric disorders:

frequent: depression

uncommon: nervousness, decreased libido

rare: abnormal dreams, sleep disorders.

Eye disorders:

very frequent: blurred vision.

unknown frequency: 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: ringing in the ears.

Cardiac and vascular disorders:

very frequent: dizziness

frequent: low blood pressure associated with fainting, cardiac rhythm disorders, chest pain, tachycardia (rapid heartbeats)

uncommon: flushing, palpitations (rapid and irregular sensation of heartbeats), myocardial infarction or stroke, possibly secondary to excessive decrease in blood pressure in high-risk patients (see section Take special care with Enalapril/Hydrochlorothiazide Combix)

rare: changes in skin color of fingers, hands, and feet, nose, or ears (Raynaud's phenomenon).

Respiratory, thoracic, and mediastinal disorders:

very frequent: cough,

frequent: difficulty breathing

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

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

very rare: acute respiratory distress (signs include severe difficulty breathing, fever, weakness, and confusion

Gastrointestinal disorders:

very frequent: nausea,

frequent: diarrhea, abdominal pain,

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

rare: infection or inflammation of the mouth mucosa, tongue inflammation

very rare: intestinal angioedema (inflammation of the intestinal wall).

Hepatobiliary disorders:

rare: liver failure, liver necrosis (which can be fatal), liver inflammation, suppression or cessation of bile secretion, yellowing of the skin or eyes, inflammation of the gallbladder (particularly in patients with pre-existing bile duct stones).

Skin and subcutaneous tissue disorders:

frequent: skin rash (exanthema)

hypersensitivity/angioedema: swelling of the face, limbs, lips, tongue, glottis, and/or larynx

uncommon: excessive sweating, itching, urticaria, hair loss

rare: skin redness, severe blistering or bleeding in the skin (Stevens-Johnson syndrome), severe skin rash with skin and hair loss, skin peeling, appearance of red spots on the skin, skin alteration, skin redness, blistering on the skin, Stevens-Johnson syndrome.

unknown frequency: 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, sun sensitivity, or other skin manifestations may also occur.

Musculoskeletal, connective tissue, and bone disorders:

frequent: muscle cramps,

uncommon: joint pain.

Renal and urinary disorders:

uncommon: renal dysfunction (alteration of kidney function), renal failure, presence of proteins in the urine

rare: inadequate urine secretion, kidney cell inflammation.

Reproductive system and breast disorders:

uncommon: impotence.

rare: increased breast size in men.

General disorders and administration site conditions:

very frequent: fatigue.

frequent: tiredness, chest pain

uncommon: general malaise, fever.

Investigations:

frequent: high potassium levels in the blood, increased serum creatinine

uncommon: increased blood urea, low sodium levels in the 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 that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Enalapril/Hydrochlorothiazide Combix

Do not store above 25°C.

Store in the original package.

Keep this medicine out of the sight and reach of children

Expiration date:Do not use this medicine after the expiration date indicated on the package. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the packages and medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of packages and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Enalapril/Hydrochlorothiazide Combix:

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

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

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

Appearance of the product and package contents:

It is presented in the form of tablets. The tablets are round, yellow, and scored on one side. Each package contains 28 or 30 tablets, and the clinical package is 500 tablets.

Marketing authorization holder and manufacturer:

Holder:

Combix Laboratories, S.L.U.

Badajoz Street 2, Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturers:

INDUSTRIA QUÍMICA Y FARMACÉUTICA VIR, S.A.

Laguna Street 66-68-70, 28923 ALCORCÓN (Madrid) Spain

MEDICINE SUBJECT TO MEDICAL PRESCRIPTION

This leaflet was approved in: January 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es