ACETENSIL PLUS 20 mg/12.5 mg TABLETS

Introduction

Package Leaflet: Information for the User

Acetensil Plus20 mg/12.5 mg tablets EFG

enalapril maleate/hydrochlorothiazide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Acetensil Plus and what is it used for
2. What you need to know before you take Acetensil Plus
3. How to take Acetensil Plus
4. Possible side effects
5. Storing Acetensil Plus
6. Contents of the pack and other information

1. What is Acetensil Plus and what is it used for

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

The enalapril component of Acetensil Plus is a medicine that belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (ACE inhibitors), which act by dilating blood vessels to make the heart pump blood to all parts of the body more easily. The hydrochlorothiazide component of Acetensil Plus belongs to a group of medicines known as thiazide diuretics (medicines that increase urine output). Together, enalapril and hydrochlorothiazide help to decrease high blood pressure.

Your doctor has prescribed Acetensil Plus 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 Acetensil Plus

Do not take Acetensil Plus

• If you are allergic to enalapril maleate, hydrochlorothiazide, or 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 as Acetensil Plus (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 liver disease.
• If you have severe kidney disease.
• If you have anuria (do not urinate).
• If you have diabetes or kidney failure and are being treated with a blood pressure-lowering medicine that contains aliskiren.
• If you are more than 3 months pregnant. (It is also best to avoid Acetensil Plus at the start of pregnancy - see section "Pregnancy").
• 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 an area such as the throat) is high.

If you are not sure if you should start taking Acetensil Plus, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Acetensil Plus.

In the following situations, your doctor may need to adjust your dose of Acetensil Plus or monitor your blood potassium levels:

• 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 shortness of breath or severe difficulty breathing after taking Acetensil Plus, go to the doctor immediately.
• If you have heart disease 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 any 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 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 diuretics, or salt substitutes that contain potassium, or other medicines that can increase potassium levels in the blood, such as heparin (a medicine used to prevent blood clots), trimethoprim, or cotrimoxazole (medicines used to treat bacterial 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 an allergy to bee or wasp stings.
• If you have low blood pressure, as the use of Acetensil Plus, especially in the first doses, can cause a sudden drop in blood pressure (you may notice dizziness or fainting, especially when standing up).
• Consult your doctor before starting to take Acetensil Plus 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 cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Acetensil Plus.
• If you are taking any of the following medicines, the risk of angioedema may increase:
• • 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.
• 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.

• Tell your doctor if you experience a decrease in vision or eye pain, as these could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, and can occur within a few hours to a week after taking Acetensil Plus. If left untreated, this can lead to permanent vision loss. You may be at greater risk if you have previously been allergic to penicillin or sulphonamides.

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 Acetensil Plus".

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

You must inform your doctor if you think you are pregnant (or might be). Acetensil Plus is not recommended at the start of pregnancy and should not be used if you are more than 3 months pregnant, as it can cause serious harm to your baby if used at this stage (see section "Pregnancy").

Children and adolescents

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

Use in the elderly

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 Acetensil Plus

Tell your doctor or pharmacist if you are using, have recently used, or might use 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 Acetensil Plus" and "Warnings and precautions").
• Blood pressure-lowering medicines (e.g., vasodilators, beta-blockers, diuretics).
• Potassium supplements (including dietary salt substitutes), potassium-sparing diuretics, and other medicines that can increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporin, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots). See also the information in the section "Warnings and precautions".
• Medicines used to treat certain mental disorders, such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics.
• Opioids (pain-relieving medicines).
• 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 cholesterol in the blood), 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 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).
• The simultaneous 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), racecadotril, or vildagliptin. This 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 Acetensil Plus" and "Warnings and precautions".

Taking Acetensil Plus with food and drinks

Acetensil Plus can be taken with or without food. Most people take Acetensil Plus with a glass of water.

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

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

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 Acetensil Plus before you become pregnant or as soon as you know you are pregnant and will advise you to take a different medicine instead of Acetensil Plus. Acetensil Plus is not recommended during pregnancy and should not be taken if you are more than 3 months pregnant, as it can cause serious harm to your baby if used from the third month of pregnancy onwards.

Breastfeeding

Tell your doctor if you are breastfeeding or about to start breastfeeding. Acetensil Plus is not recommended for mothers who are breastfeeding.

The two active substances in Acetensil Plus, enalapril and hydrochlorothiazide, pass into breast milk. If you are breastfeeding or plan to breastfeed, consult your doctor.

Driving and using machines

Acetensil Plus is unlikely to 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 start. If you experience these effects, you should consult your doctor before performing these activities.

Acetensil Plus 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.

Acetensil Plus contains sodium

This medicine contains less than 1 mmol of sodium (23 mg per 1 mmol) per tablet; this is essentially "sodium-free".

Use in athletes

This medicine contains hydrochlorothiazide, which may produce a positive result in doping tests.

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 Acetensil Plus, as it may alter the test results.

3. How to take Acetensil Plus

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are unsure, 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.

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

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

Use in patients 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.

Acetensil Plus can be taken before or after meals.

If you take more Acetensil Plus than you should

If you have taken more Acetensil Plus 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 packaging and the leaflet of the medicine 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 Acetensil Plus

You should take Acetensil Plus exactly as your doctor has indicated. Do not take a double dose to make up for forgotten doses. Just take the next dose as usual.

If you stop taking Acetensil Plus

Your doctor will indicate the duration of your treatment with Acetensil Plus. Do not stop treatment before this, even if you feel better.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not 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 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 diseases.

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 unknown: decreased vision or eye pain due to high pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion)].

Ear and labyrinth disorders:

Infrequent: ringing in the ears.

Cardiac and vascular disorders:

Very frequent: dizziness

Frequent*: low blood pressure associated with fainting, heart rhythm disorders, angina pectoris, tachycardia (rapid heartbeats)

Infrequent: 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 "Warnings and precautions" section)

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

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 disorders, 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 skin 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 observed that may include 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 proteins in the urine

Rare*: inadequate urine secretion, kidney cell inflammation.

Reproductive system and breast disorders:

Infrequent: impotence

Rare: increased breast size in men.

General disorders and administration site conditions:

Very frequent: fatigue

Frequent: chest pain, fatigue

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 Acetensil Plus.

† The frequency of muscle spasms as "frequent" applies to hydrochlorothiazide doses of 12.5 mg and 25 mg, as found in Acetensil Plus, 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. Storage of Acetensil Plus

Keep out of sight and reach of children.

Do not store at a temperature above 25°C.

Store in the original packaging.

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

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Acetensil Plus

• The active ingredients are enalapril in the form of maleate and hydrochlorothiazide. Each tablet contains 20 mg of enalapril maleate and 12.5 mg of hydrochlorothiazide.

• The other components 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.

Marketing authorization holder

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850 – Torrejón de Ardoz (Madrid)

Spain

Manufacturer

Laboratorios Medicamentos Internacionales S.A.

Solana, 26

28850 – Torrejón de Ardoz (Madrid)

Spain

Date of the last revision of this prospectus:12/2023

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