Enalapril/hydrochlorothiazide Vir 20/12.5 mg tablets EFG

Patient Information Leaflet

Introduction

Patient Information Leaflet

Enalapril/Hydrochlorothiazide Vir 20 mg/12.5 mg tablets EFG

Read the entire patient information leaflet carefully before you start taking this medicine, as it contains important information for you. Keep this leaflet, as you may need to read it again. If you have any questions, consult your doctor or pharmacist. This medicine has been prescribed for you alone and must not be given to other people, even if they have the same symptoms as you, since it could harm them. If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Package leaflet:

1. What Enalapril/Hydrochlorothiazide Vir is and what it is used for.
2. What you need to know before taking Enalapril/Hydrochlorothiazide Vir.
3. How to take Enalapril/Hydrochlorothiazide Vir.
4. Possible side effects.
5. How to store Enalapril/Hydrochlorothiazide Vir.
6. Contents of the pack and other information.

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

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

The component enalapril is a medicine that belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (ACE inhibitors), which works by dilating blood vessels, allowing the heart to pump blood more easily to all parts of the body.

The component hydrochlorothiazide belongs to a group of medicines known as thiazide diuretics (medicines that increase urine elimination).

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 an ACE inhibitor alone.

2. What you need to know before taking 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 sulfonamide-derived substances. Ask your doctor if you are unsure about what sulfonamide-derived medicines are.
• If you have previously been treated with a medicine from the same group as Enalapril/Hydrochlorothiazide Vir (ACE inhibitors) and experienced allergic reactions with swelling of the face, lips, tongue, and/or throat, accompanied by 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 disorder causing swelling in the face and airways, and abdominal cramps).
• If you have severe kidney disease.
• If you suffer from anuria (you do not produce urine).
• 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 (Enalapril/Hydrochlorothiazide Vir should also be avoided in early pregnancy – see Pregnancy section).
• If you are being treated with sacubitril/valsartan, a medicine for heart failure.

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

Warnings and precautions

Talk to your doctor or pharmacist before starting 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 involving narrowing of heart valves (mitral or aortic stenosis) or other conditions that reduce 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 taking high doses of medicines that increase urine output).

• If you have blood disorders.

• If you have diabetes and are taking medicines for diabetes, including insulin, as your diabetes treatment may require dose adjustments. 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, take potassium supplements, potassium-sparing medicines (medicines that increase potassium levels), potassium-containing salt substitutes, or other medicines that may increase blood potassium, such as heparin (a medicine used to prevent blood clots), trimethoprim-containing medicines, or cotrimoxazole (also known as trimethoprim/sulfamethoxazole, used to treat infections).

• If you develop an allergic reaction during treatment with swelling of the face, lips, tongue, and/or throat, with difficulty swallowing or breathing. Note that patients of Black race are more susceptible to this type of medicine.

• 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 when levels are excessively high).

• If you are scheduled 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/hydrochlorothiazide, especially with the first doses, may cause a sudden drop in blood pressure (you may feel faint or dizzy, particularly with initial doses and when standing up).

• Consult your doctor before starting enalapril/hydrochlorothiazide if you have had skin cancer or if you 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 and lip cancer. Protect your skin from exposure to sunlight and UV rays while taking enalapril/hydrochlorothiazide.

• If you are taking a medicine containing a neprilysin inhibitor such as sacubitril (available in a fixed-dose combination with valsartan), used in patients with heart failure, or racecadotril, used in patients with acute diarrhea. You may have an increased risk of an allergic reaction called angioedema.

• Inform your doctor if you are taking any of the following medicines for high blood pressure:

  • 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 loss or eye pain, these could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which may occur within hours to one 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 develop shortness of breath or severe breathing difficulty 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 (including at the dentist), inform the doctor or dentist that you are taking enalapril/hydrochlorothiazide, as you may experience a sudden drop in blood pressure due to anesthesia.

Inform your doctor if you think you are pregnant (or could be). Enalapril/hydrochlorothiazide is not recommended in early pregnancy and must not be used if you are more than 3 months pregnant, as it may cause serious harm to your baby if used during this period (see Pregnancy section).

Children and adolescents

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

Use in elderly patients

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

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

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 information under the headings “Do not take Enalapril/Hydrochlorothiazide Vir” and “Warnings and precautions”).
• Antihypertensive medicines (reduce high blood pressure), e.g., vasodilators, beta-blockers, diuretics.
• Potassium-containing medicines (including dietary salt substitutes) or other medicines that may increase blood potassium, such as heparin (a medicine used to prevent blood clots), trimethoprim-containing medicines, or cotrimoxazole (also known as trimethoprim/sulfamethoxazole, used to treat bacterial infections); cyclosporine, a medicine.
• Medicines used to treat certain mental disorders, such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics.
• Opioid analgesics (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), like acetylsalicylic acid, including 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 (which prevent blood clot formation).
• Calcium salts and vitamin D.
• Ion-exchange resins (medicines used to lower blood cholesterol), such as cholestyramine and colestipol.
• Antiarrhythmics (medicines used for prevention and control of heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medicines (which slow gastric emptying), 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 (medicines to treat 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 (medicines to treat certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases such as rheumatoid arthritis).
• Concomitant administration of mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may increase the risk of an allergic reaction called angioedema.
• A medicine containing a neprilysin inhibitor such as sacubitril (available in a fixed-dose combination with valsartan) or racecadotril. This may increase the risk of angioedema (swelling of the face, lips, tongue, or throat with difficulty swallowing or breathing). See also 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 enhance the blood pressure-lowering (hypotensive) effect of this medicine.

Pregnancy and breastfeeding:

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Your doctor will usually advise you to stop taking Enalapril/Hydrochlorothiazide Vir before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Enalapril/Hydrochlorothiazide Vir is not recommended during 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 from the third month of pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding or about to start breastfeeding. Enalapril/Hydrochlorothiazide is not recommended for breastfeeding mothers.

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

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 operating machinery

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

Enalapril/Hydrochlorothiazide Vir contains lactose

This medicine contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult him 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 Vir

Follow exactly the instructions for use of this medicine provided by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Remember to take your medicine.

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

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

The recommended dose is one or two tablets taken once daily. Take enalapril/hydrochlorothiazide every day, exactly as directed by your doctor. It is very important that you continue taking this medicine for as long as your doctor has prescribed it. Do not take more tablets than the prescribed dose.

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

Patients with impaired kidney 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 tablets with a glass of water.

This medicine may 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, contact your doctor, pharmacist, or call the Toxicology Information Service immediately, telephone: 91-562 04 20, indicating the medicine and the amount taken.

It is recommended to bring the medicine's packaging and leaflet to 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 output, and/or tachycardia.

If you forget to take Enalapril/Hydrochlorothiazide Vir:

You should take this medicine as prescribed by your doctor. Do not take a double dose to make up for missed doses. Simply take the next dose in the usual way.

If you stop treatment with Enalapril/Hydrochlorothiazide Vir

Your doctor will advise you on the duration of your treatment.

Do not stop treatment early, 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 about 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 everyone experiences them.

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

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

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

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

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

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

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).

Blood and lymphatic system disorders:

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

Rare: reduction in a type of white blood cells (neutrophils), decrease in hemoglobin (the 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 (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: high potassium levels in blood, increased cholesterol, increased triglycerides, increased uric acid in blood

Uncommon: low blood glucose and magnesium levels, gout

Rare: increased blood glucose

Very rare: high calcium levels in blood

Nervous system disorders:

Common: headache, fainting, taste disturbances

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 elevated 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 common: dizziness

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

Uncommon: flushing, palpitations (rapid and irregular heartbeat sensation), myocardial infarction or stroke, possibly secondary to excessive blood pressure reduction in high-risk patients (see section "Special warnings and precautions for use" of Enalapril/Hydrochlorothiazide Vir)

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), inflammation of nasal mucosa, allergic alveolitis (inflammation of 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 respiratory 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, vomiting, digestive discomfort, constipation, loss of appetite, gastric irritation, dry mouth, peptic ulcer, flatulence (gas)

Rare: infection or inflammation of the mouth mucosa, 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, gallbladder inflammation (particularly in patients with pre-existing gallstone formation in the biliary tract).

Skin and subcutaneous tissue disorders:

Common: skin rash (exanthema), hypersensitivity/angioneurotic edema: 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 of 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.

A symptomatic complex has been reported that may include any or all of the following symptoms: fever, serositis, vasculitis, muscle pain/swelling, joint pain/swelling, 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: reduced urine output, inflammation of kidney cells.

Reproductive system and breast disorders:

Uncommon: impotence

Rare: breast enlargement in men.

General disorders and administration site conditions:

Very common: tiredness

Common: fatigue, chest pain

Uncommon: general malaise, fever

Investigations:

Common: high potassium levels in blood, increased serum creatinine

Uncommon: increased blood urea, low sodium levels in blood

Rare: increased liver enzymes, increased serum bilirubin.

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

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

Reporting of adverse effects:

If you experience any adverse effect, talk to 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 Vir

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

Do not store above 25°C.

Store in the original container.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to 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 Vir 20/12.5 mg

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 (E-500), corn starch, pregelatinized corn starch, magnesium stearate (E-572) and yellow iron oxide (E-172).

Appearance of the product and contents of the pack:

It is presented in packs of 28 tablets. The tablets are round, yellow in colour 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 leaflet was last approved in: January 2022

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