ENALAPRIL/HYDROCHLOROTHIAZIDE VIR 20/12.5 mg TABLETS

Introduction

Package Leaflet: Information for the User.

Enalapril/Hydrochlorothiazide Vir 20 mg/12.5 mg Tablets EFG

Contents of the pack:

1. What is Enalapril/Hydrochlorothiazide Vir and what is it used for.
2. What you need to know before you take Enalapril/Hydrochlorothiazide Vir.
3. How to take Enalapril/Hydrochlorothiazide Vir.
4. Possible side effects.
5. Storage of Enalapril/Hydrochlorothiazide Vir.
6. Pack contents and further information.

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

This medicine contains two active substances: enalapril and hydrochlorothiazide, which belong to the group of antihypertensives and, by different mechanisms, reduce high blood pressure.

The enalapril component is a medicine that belongs to a group of medicines 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 hydrochlorothiazide component belongs to the group of medicines known as thiazide diuretics (medicines that increase urine production).

Together, enalapril and hydrochlorothiazide help to decrease 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. What you need to know before you take Enalapril/Hydrochlorothiazide Vir

Do not take Enalapril/Hydrochlorothiazide Vir:

• If you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to sulphonamide-derived substances. Ask your doctor if you are not sure what sulphonamide-derived medicines are.
• If you have previously been treated with a medicine from the same group of medicines as Enalapril/Hydrochlorothiazide Vir (ACE inhibitors), and have had allergic reactions with swelling of the face, lips, tongue and/or throat with 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 (an immune system disease that causes inflammation in the face and respiratory tract, and abdominal colic).
• 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 (It is also best to avoid Enalapril/Hydrochlorothiazide Vir at the beginning of pregnancy - see section Pregnancy).
• If you are being treated with sacubitril/valsartan, a medicine for heart failure.

If you are not sure if you should start taking Enalapril/Hydrochlorothiazide Vir, consult your doctor.

Warnings and precautions

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

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

• If you have heart disease with narrowing of the heart valves (mitral or aortic stenosis) or other factors that reduce left ventricular outflow (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 any blood disorders.
• If you have diabetes and are taking medicines to treat diabetes, including insulin, as you 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 these can cause high potassium levels in the blood, which can be serious.
• If you are undergoing dialysis. If you follow a salt-free diet, take potassium supplements, potassium-sparing medicines (medicines that increase potassium levels), potassium-containing salt substitutes, or other medicines that can increase blood potassium levels, such as heparin (a medicine used to prevent blood clots), trimethoprim or cotrimoxazole, also known as trimethoprim/sulfamethoxazole (medicines used to treat infections).
• If you experience an allergic reaction with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing during treatment. You should be aware that black patients are more sensitive to this type of medicine.
• If you are about to undergo a treatment called LDL apheresis (a procedure similar to dialysis to remove bad cholesterol from the blood in cases where it is excessively high).
• If you are going to undergo desensitization treatment to reduce the effect of a bee or wasp sting allergy.
• If you have low blood pressure, as the use of enalapril/hydrochlorothiazide, especially in the first doses, can cause a sudden drop in blood pressure (you may notice dizziness or fainting, especially in the initial doses and when standing up).
• Consult your doctor before starting to take enalapril/hydrochlorothiazide 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 and UV exposure while taking enalapril/hydrochlorothiazide.
• If you are taking a medicine that contains a neprilysin inhibitor, such as sacubitril (available in a fixed-dose combination with valsartan), used in patients with heart failure, and racecadotril, used in patients with acute diarrhea. You may be at greater risk of experiencing an allergic reaction called angioedema.
• Tell your doctor if you are taking any of the following medicines used to treat high blood pressure:
• • An angiotensin II receptor antagonist (ARA) (also known as "sartans" - e.g., valsartan, telmisartan, irbesartan), especially if you have diabetes-related kidney problems.
  • 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 Vir.
• If you have had respiratory or lung 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 Vir, 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 Vir”.

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

You should tell 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 used if you are pregnant for more than 3 months, as it can cause serious harm to your baby if used during this period (see section Pregnancy).

Children and adolescents

The safety and efficacy of enalapril/hydrochlorothiazide in this population have not been established, 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.

Other medicines and Enalapril/Hydrochlorothiazide VirTell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Your doctor may need to change your dose and/or take other precautions.

It is especially important that you tell 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 Vir” and “Warnings or precautions”).
• Blood pressure-lowering medicines (e.g., vasodilators, beta-blockers, diuretics).
• Potassium-containing medicines (including dietary salt substitutes) or other medicines that can increase blood potassium levels, such as heparin (a medicine used to prevent blood clots), trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole (medicines used to treat bacterial infections).
• 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 antidiabetics (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 (which prevent blood clot formation).
• Calcium salts and vitamin D.
• Ion exchange resins (medicines used to lower blood cholesterol), such as cholestyramine and colestipol.
• Antiarrhythmic medicines (used to prevent and control heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medicines (which 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.
• Immunosuppressive medicines (used to prevent organ rejection in transplants), such as cyclosporine.
• Antibiotics (medicines used to treat certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases, such as rheumatoid arthritis).
• The concomitant administration of mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may increase the risk of an allergic reaction called angioedema.
• A medicine that contains a neprilysin inhibitor, such as sacubitril (available in a fixed-dose combination with valsartan), and racecadotril. It 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-Hydrochlorothiazide Vir” and “Warnings and precautions”.

Taking Enalapril/Hydrochlorothiazide Vir with food and drinks:

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

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

Pregnancy and breastfeeding:

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. Normally, your doctor will advise you to stop taking Enalapril/Hydrochlorothiazide Vir 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 Vir. Enalapril/Hydrochlorothiazide Vir is not recommended during pregnancy and should not be taken if you are pregnant for more than 3 months, as it can cause serious harm to your baby if used from the third month of pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding or about to start breastfeeding. Enalapril/hydrochlorothiazide is not recommended in breastfeeding mothers.

The two active substances of Enalapril/Hydrochlorothiazide Vir, enalapril and hydrochlorothiazide, pass into breast milk. If you are breastfeeding or plan to breastfeed, consult your doctor.

Use in athletes

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

Driving and using machines

It is unlikely that enalapril/hydrochlorothiazide will affect your ability to drive or use machines. However, you may occasionally experience dizziness or fatigue during treatment for high blood pressure, especially at the beginning. If you experience these effects, you should consult your doctor before performing these activities.

Enalapril/Hydrochlorothiazide Vir contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult 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 Vir

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

Remember to take your medicine.

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

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

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

Patient with impaired kidney function:

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

Method of administration

This medicine is administered orally.

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

This medicine can be taken before or after meals.

If you take more Enalapril/Hydrochlorothiazide Vir than you should

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

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

The most likely symptoms would be: 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 Vir:

You should take this medicine as your doctor has prescribed. 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 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 medicine unless your doctor tells you to do so.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause 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)

Infrequent: (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)

Benign, malignant, and unspecified neoplasms (including cysts and polyps):

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

Disorders of the blood and lymphatic system:

Infrequent: decrease in red blood cells (cells that carry oxygen in the blood)

Rare: reduction of a type of white blood cell (neutrophils), decrease in hemoglobin (protein in red blood cells that carries 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 disorders.

Endocrine disorders:

Frequency not known: 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

Infrequent: 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

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

Rare: paralysis (due to low potassium levels).

Psychiatric disorders:

Frequent: depression

Infrequent: nervousness, decreased libido*

Rare: abnormal dreams, sleep disorders.

Eye disorders:

Very frequent: 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 effusion) or acute angle-closure glaucoma.

Ear and labyrinth disorders:

Infrequent: 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)

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

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

Respiratory, thoracic, and mediastinal disorders:

Very frequent: cough,

Frequent: difficulty breathing.

Infrequent: 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 pulmonary alveolus due to allergy)/eosinophilic pneumonia (disease in which a type of white blood cell, called eosinophils, accumulates 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,

Infrequent: 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 stone formation).

Disorders of the skin and subcutaneous tissue:

Frequent: skin rash (exanthema), hypersensitivity/angioneurotic edema: swelling of the face, limbs, lips, tongue, glottis, and/or larynx

Infrequent: excessive sweating, itching, urticaria, hair loss

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

A symptomatic complex has been reported that may include all or some of the following symptoms: 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†

Infrequent: joint pain*.

Renal and urinary disorders:

Infrequent: renal dysfunction (alteration of kidney function), renal failure, presence of protein in the urine

Rare: inadequate urine secretion, inflammation of kidney cells.

Reproductive system and breast disorders:

Infrequent: impotence.

Rare: breast enlargement in men.

General disorders and administration site conditions:

Very frequent: fatigue.

Frequent: tiredness, chest pain

Infrequent: general malaise, fever.

Investigations:

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

Infrequent: increased blood urea, low sodium levels in the blood

Rare: increased liver enzymes, increased serum bilirubin.

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

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

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 does not appear in this prospectus. 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. Conservation of Enalapril/Hydrochlorothiazide Vir

Keep this medicine out of sight and reach of children.

Do not store at a temperature above 25°C.

Store in the original package.

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

Medicines should not be thrown away through wastewater or household waste. Deposit the packages and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packages and medicines you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Enalapril/Hydrochlorothiazide Vir 20/12.5 mg

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

Appearance of the product and package contents:

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

Marketing authorization holder and manufacturer:

Marketing authorization holder

Industria Química y Farmacéutica Vir, S.A.

C/ Laguna 66-70, Polígono Industrial Urtinsa II

28923 Alcorcón (Madrid)

Spain

Manufacturer:

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 prospectus was approved in:January 2022

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