Label: Information for the user.

Enalapril/Hidroclorotiazida Vir 20 mg/12.5 mg tablets EFG

This medication contains two active ingredients: enalapril and hidroclorotiazida, which belong to the group of anti-hypertensives and, through different mechanisms, reduce elevated blood pressure.

The enalapril component is a medication that belongs to a group of medications known as angiotensin-converting enzyme inhibitors (ACE inhibitors), which acts by dilating blood vessels, making it easier for the heart to pump blood to all parts of the body.

The hidroclorotiazida component belongs to a group of medications known as thiazide diuretics (medications that increase the elimination of urine).

Together, enalapril and hidroclorotiazida help to decrease elevated blood pressure.

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

Do not take Enalapril/Hidroclorotiazida Vir:

• If you are allergic to the active ingredients or any of the other components of this medication (listed in section 6).
• If you are allergic to sulfonamide derivatives. Ask your doctor if you are unsure what sulfonamide derivatives are.
• If you have previously been treated with a medication from the same group as Enalapril/Hidroclorotiazida Vir (angiotensin-converting enzyme inhibitors), and have had allergic reactions with swelling of the face, lips, tongue, and/or throat, difficulty swallowing or breathing.
• If you have had such allergic reactions without a known cause, or if you have been diagnosed with hereditary or idiopathic angioedema (a condition of the immune system that causes inflammation in the face and respiratory tract, and abdominal cramps).
• If you have severe kidney disease.
• If you are anuric (do not urinate).
• If you have severe liver disease.
• If you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskirén.
• If you are more than 3 months pregnant (It is also recommended to avoid Enalapril/Hidroclorotiazida Vir at the beginning of pregnancy - see Pregnancy section).
• If you are being treated with sacubitrilo/valsartán, a medication for heart failure.

If you are unsure whether you should start taking Enalapril/Hidroclorotiazida Vir, consult your doctor.

Warnings and precautions:

Consult your doctor or pharmacist before starting to take Enalapril/Hidroclorotiazida Vir.

Your doctor may need to adjust your dose of Enalapril/Hidroclorotiazida Vir or monitor your blood potassium levels in the following situations:

• If you have heart disease with narrowing of the heart valves (mitral or aortic stenosis) or other factors that reduce blood flow to the left chamber of the heart (hypertrophic obstructive cardiomyopathy).
• If you have conditions that reduce the volume of fluids or sodium levels in the body (e.g., intense vomiting, diarrhea, or if you are being treated with high doses of medications that increase urine production).
• If you have any blood abnormalities.
• If you have diabetes, and are taking medications to treat diabetes, including insulin, as you may need to adjust the dose of the diabetes medications. Diabetes can cause high potassium levels in the blood that can be severe.
• If you have liver problems.
• If you have kidney problems (including kidney transplant), as these can cause high potassium levels in the blood that can be severe.
• If you are undergoing dialysis. If you are following a low-sodium diet, taking potassium supplements, medications that conserve potassium (medications that increase potassium levels), potassium-containing salt substitutes, or other medications that may increase blood potassium levels, such as heparin (a medication used to prevent blood clots), trimethoprim/sulfamethoxazole (medications used to treat infections), or other medications that may increase blood potassium levels.
• If you experience an allergic reaction with swelling of the face, lips, tongue, and/or throat, difficulty swallowing or breathing. Note that patients of black race are more sensitive to this type of medication.
• If you are about to undergo a treatment called LDL apheresis (a procedure similar to dialysis, to remove LDL or bad cholesterol particles from the blood in cases where it is excessively elevated).
• If you are about to undergo desensitization treatment to reduce the effect of an allergy to bee or wasp stings.
• If you have low blood pressure, as the use of enalapril/hidroclorotiazida, especially in the initial doses, may cause a sudden drop in blood pressure (you may feel dizzy or lightheaded, especially in the initial doses and when standing up).
• Consult your doctor before starting to take enalapril/hidroclorotiazida if you have had skin cancer or if you develop an unexpected skin lesion during treatment. The treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking enalapril/hidroclorotiazida.
• If you are taking a medication that contains a neprilysin inhibitor such as sacubitrilo (available in a fixed-dose combination with valsartán), used in patients with heart failure, and racecadotrilo, used in patients with acute diarrhea. You may have a higher risk of experiencing an allergic reaction called angioedema.
• Inform your doctor if you are taking any of the following medications used to treat high blood pressure:
• • An angiotensin II receptor antagonist (ARA) (also known as "sartanes" - for example, valsartán, telmisartán, irbesartán), particularly if you have kidney problems related to diabetes.
  • Aliskirén

• If you experience a decrease in vision or eye pain, it may be a symptom of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, which can occur within a few hours to a week after taking Enalapril/Hidroclorotiazida Vir.
• 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 shortness of breath or severe difficulty breathing after taking Enalapril/Hidroclorotiazida Vir, seek medical attention immediately.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels in the blood (e.g., potassium) at regular intervals.

See also the information under the heading “Do not take Enalapril/Hidroclorotiazida Vir”.

Before undergoing surgery or anesthesia (including dental consultation), inform your doctor or dentist that you are taking enalapril/hidroclorotiazida, as you may experience a sudden drop in blood pressure due to the anesthesia.

Inform your doctor if you think you may be pregnant (or could be pregnant). Enalapril/hidroclorotiazida is not recommended at the beginning of pregnancy and should not be used if you are more than 3 months pregnant, as it may cause severe damage to your baby if used during this period (see Pregnancy section).

Children and adolescents:

The safety and efficacy of enalapril/hidroclorotiazida have not been established in this age group, so it is not recommended for use in children.

Use in elderly patients:

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

Other medications and Enalapril/Hidroclorotiazida Vir:Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. Your doctor may need to adjust your dose and/or take other precautions.

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

• An angiotensin II receptor antagonist (ARA) or aliskirén (see also the information under the headings “Do not take Enalapril/Hidroclorotiazida Vir” and “Warnings and precautions”).
• Anti-hypertensive medications (reduce elevated blood pressure), for example, vasodilators, beta-blockers, diuretics.
• Medications with potassium (including dietary salt substitutes) or other medications that may increase blood potassium levels, such as heparin (a medication used to prevent blood clots), trimethoprim/sulfamethoxazole (medications used to treat infections), or other medications that may increase blood potassium levels.
• Medications used to treat certain mental disorders, such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics.
• Opioids (medications used to treat intense pain).
• Medications used to treat diabetes, such as insulin or oral antidiabetic medications (e.g., metformin).
• Medications used to treat pain or certain inflammation, such as nonsteroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, including selective cyclooxygenase-2 (COX-2) inhibitors.
• Sympathomimetic medications (medications used in the treatment of certain heart and blood vessel disorders and some medications for colds).
• Amines, such as noradrenaline.
• Muscle relaxants, such as tubocurarine.
• Thrombolytic medications (that prevent blood clot formation).
• Calcium salts and vitamin D.
• Ionic exchange resins (medications used to reduce cholesterol in the blood), such as cholestyramine and colestipol.
• Antiarrhythmic medications (medications used to prevent and control heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medications (medications that decrease gastric emptying rate), such as atropine (used before general anesthesia or to prevent spasms) or biperiden (used in patients with Parkinson's disease).
• Medications used to treat gout, such as probenecid, sulfinpyrazone, and allopurinol.
• Antiviral medications (medications used to treat viral infections), such as amantadine.
• Cytotoxic medications (used to treat cancer), such as cyclophosphamide and methotrexate.
• Immunosuppressive medications (used to prevent rejection in organ transplants), such as cyclosporine.
• Antibiotics (medications used to treat certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases such as rheumatoid arthritis).
• The simultaneous administration of mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may increase the risk of an allergic reaction called angioedema.
• A medication containing a neprilysin inhibitor such as sacubitrilo (available in a fixed-dose combination with valsartán) and racecadotrilo may increase the risk of angioedema (swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing). See also the information in the sections “Do not take Enalapril/Hidroclorotiazida Vir” and “Warnings and precautions”.

Enalapril/Hidroclorotiazida Vir with food and beverages:

Enalapril/Hidroclorotiazida Vir can be taken with or without food.

Alcohol may increase the hypotensive effect of this medication.

Pregnancy and lactation:

Pregnancy

If you are pregnant or think you may be pregnant, consult your doctor before using this medication. Your doctor will usually advise you to stop taking Enalapril/Hidroclorotiazida Vir before becoming pregnant or as soon as you know you are pregnant and will advise you to take a different medication instead of Enalapril/Hidroclorotiazida Vir. Enalapril/Hidroclorotiazida Vir is not recommended during pregnancy and should not be used if you are more than 3 months pregnant, as it may cause severe damage to your baby if used during this period (see Pregnancy section).

Lactation

Inform your doctor if you are breastfeeding or plan to start breastfeeding. Enalapril/hidroclorotiazida is not recommended for mothers who are breastfeeding.

The two active ingredients of Enalapril/Hidroclorotiazida Vir, enalapril, and hydrochlorothiazide, pass into breast milk. If you are breastfeeding your baby or plan to do so, consult your doctor.

Use in athletes:

Inform athletes that this medication contains a component that may produce a positive result in doping control tests.

Driving and operating machinery:

It is unlikely that enalapril/hidroclorotiazida will affect your ability to drive or operate machinery. However, you may occasionally experience dizziness or fatigue during the treatment of high blood pressure, especially at the beginning. If you experience these effects, consult your doctor before engaging in these activities.

Enalapril/Hidroclorotiazida Vir contains lactose:

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

Interference with diagnostic tests:

If you need to undergo any diagnostic tests to evaluate parathyroid gland function, inform your doctor that you are taking enalapril/hidroclorotiazida, as it may alter the test results.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Remember to take your medication.

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

Take your medication every day, exactly as indicated by your doctor. It is very important that you continue taking this medication for the time your doctor prescribes. Do not take more tablets than the prescribed dose.

The recommended dose is one or two tablets administered once a day. Take enalapril/hydrochlorothiazide every day, exactly as indicated by your doctor. It is very important that you continue taking this medication for the time your doctor prescribes. Do not take more tablets than the prescribed dose.

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

Patients with altered kidney function:

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

Administration form

This medication is administered orally.

Take the tablets with the help of a glass of water.

This medication can be taken before or after meals

If you take more Enalapril/Hidrochlorothiazide Vir than you should

If you have taken more enalapril/hydrochlorothiazide than you should, consult your doctor, pharmacist, or call the Toxicological Information Service, Telephone: 91-562 04 20, indicating the medication and the amount taken.

It is recommended to bring the packaging and the medication leaflet to the healthcare staff.

The most likely symptoms would be: a feeling of dizziness or vertigo due to a sudden or excessive drop in blood pressure, and/or excessive thirst, disorientation, decreased urine production, and/or tachycardia.

If you forgot to take Enalapril/Hidrochlorothiazide Vir:

You should take this medication as your doctor prescribed. Do not take a double dose to compensate for the missed doses. Limit yourself to taking the next dose in the usual manner.

If you interrupt the treatment with Enalapril/Hidrochlorothiazide Vir

Your doctor will indicate the duration of your treatment.

Do not stop treatment before, even if you feel better.

Do not stop taking your medication unless your doctor tells you to.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The recorded side effects are listed below according to the following frequencies:

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

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

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

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

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

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

Malignant, benign, and unspecified neoplasms (including cysts and polyps):

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

Blood and lymphatic system disorders:

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

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

Endocrine disorders:

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

Metabolism and nutrition disorders:

Common: 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 levels in the blood

Very rare: high calcium levels in the blood

Nervous system disorders:

Common: headache, dizziness, altered taste

Uncommon: confusion, drowsiness, insomnia, numbness, vertigo

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 high pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma.

Ear and labyrinth disorders:

Uncommon: ringing in the ears.

Cardiac and vascular disorders:

Very common: dizziness

Common: hypotension associated with fainting, cardiac rhythm disorders, angina pectoris, tachycardia (rapid heartbeats)

Uncommon: flushing, palpitations (rapid and irregular heartbeats), myocardial infarction or stroke, possibly secondary to excessive hypotension in high-risk patients (see section Be careful with Enalapril/Hidroclorotiazida Vir)

Rare: changes in skin color of hands and feet, 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 distress (including pneumonia and pulmonary edema), inflammation of nasal mucosa, allergic alveolitis (inflammation of the alveolar lung by allergy)/eosinophilic pneumonia (disease in which a type of white blood cell, called eosinophils, accumulates in the lungs).

Very rare: Acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion

Gastrointestinal disorders:

Very common: nausea,

Common: diarrhea, abdominal pain,

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

Rare: infection or inflammation of the oral mucosa, inflammation of the tongue

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

Hepatobiliary disorders:

Rare: liver insufficiency, 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 formation of stones in the bile ducts).

Skin and subcutaneous tissue disorders:

Common: skin rash (exanthema), angioneuritic edema: swelling of the face, extremities, lips, tongue, glottis, and/or larynx

Uncommon: excessive sweating, itching, urticaria, hair loss

Rare: skin redness, severe blistering or hemorrhaging 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, vesicles on the skin.

A complex of symptoms has been reported that may include any or all of the following symptoms: fever, serositis, vasculitis, muscle and joint inflammation, positive antinuclear antibodies test, increased erythrocyte sedimentation rate, eosinophilia, and leukocytosis. It may also cause skin rash, sensitivity to sunlight, or other skin manifestations.

Musculoskeletal, connective tissue, and bone disorders:

Common: muscle cramps†

Uncommon: joint pain*.

Renal and urinary disorders:

Uncommon: renal dysfunction (alteration of kidney function), renal insufficiency, proteinuria

Rare: oliguria, renal cell inflammation.

Reproductive and breast disorders:

Uncommon: impotence.

Rare: breast enlargement in men.

General disorders and administration site conditions:

Very common: fatigue.

Common: fatigue, chest pain

Uncommon: general malaise, fever.

Investigations:

Common: high potassium levels in the blood, increases in serum creatinine

Uncommon: increases in blood urea, low sodium levels in the blood

Rare: increases in liver enzymes, increases in serum bilirubin.

*Only observed with 12.5 mg and 25 mg doses of hydrochlorothiazide, as found in Enalapril/Hidroclorotiazida Vir.

†The frequency of muscle cramps as "common" applies to the 12.5 mg and 25 mg doses of hydrochlorothiazide, as found in Enalapril/Hidroclorotiazida Vir, although the frequency of the event is "uncommon", and applies to the 6 mg dose of hydrochlorothiazide.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not store at a temperature above 25°C.

Store in the original packaging.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Enalapril/Hidroclorotiazida Vir 20/12,5 mg

The active principles are enalapril in the form of maleate and hidroclorotiazida. Each tablet contains 20 mg of enalapril and 12.5 mg of hidroclorotiazida.

• The other components (excipients) are: lactose monohydrate, sodium hydrogen carbonate (E-500), cornstarch, pregelatinized cornstarch, magnesium stearate (E-572) and yellow iron oxide (E-172).

Appearance of the product and contents of the packaging:

It is presented in packaging of 28 tablets. The tablets are yellow, round and scored on one face.

Holder of the marketing authorization and responsible for manufacturing:

Holderof the marketing authorization

Industria Química y Farmacéutica Vir, S.A.

C/ Laguna 66-70, Polígono Industrial Urtinsa II

28923 Alcorcón (Madrid)

Spain

Responsible for manufacturing:

Industria Química y Farmacéutica VIR, S.A.

C/ Laguna 66-70, Polígono Industrial Urtinsa II

28923 Alcorcón (Madrid)

Spain

or

Toll Manufacturing Services, S.L.

C/Aragoneses 2

28108 Alcobendas (Madrid).

Spain

This leaflet has been approved in:January 2022

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es