ENALAPRIL/HYDROCHLOROTHIAZIDE TARBIS 20 mg/12.5 mg TABLETS

2. What you need to know before you take Enalapril/Hydrochlorothiazide Tarbis

Do not take Enalapril/Hydrochlorothiazide Tarbis:

• 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 not sure what sulfonamide-derived medicines are.
• If you have been treated with a medicine from the same group as enalapril/hydrochlorothiazide (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 (a disease of the immune system 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 (you do not urinate).
• If you have diabetes or kidney problems 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 Tarbis at the beginning of pregnancy - see section pregnancy).
• If you have taken or are 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 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.

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

Warnings and precautions:

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

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

• If you have a heart disease that involves narrowing of the heart valves (mitral or aortic stenosis) or other factors that reduce the flow of the left ventricle of the heart (hypertrophic cardiomyopathy).
• If you have disorders that reduce the volume of fluids or the sodium level 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 the dose of these medicines may need to be adjusted. Diabetes can cause high levels of potassium 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 levels of potassium in the blood, which can be serious.
• If you are undergoing dialysis.
• If you follow a low-salt diet, take potassium supplements, potassium-sparing diuretics, or other medicines that can increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots).
• If during treatment, an allergic reaction occurs with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing. 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 treatment 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 enalapril/hydrochlorothiazide, especially in the first doses, can cause a sudden drop in blood pressure (you may notice it as fainting or dizziness, especially when standing up).
• 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 kidney problems related to diabetes.
  • Aliskiren

• 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 skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Enalapril/Hydrochlorothiazide Tarbis.
• 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 increased pressure in the eye, and can occur within a few hours to a week after taking Enalapril/Hydrochlorothiazide Tarbis.
• 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 Enalapril/Hydrochlorothiazide Tarbis, 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 Tarbis".

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

You must inform your doctor if you think you are pregnant (or might be). Enalapril/Hydrochlorothiazide Tarbis is not recommended during 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

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

Using Enalapril/Hydrochlorothiazide Tarbis with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription, homeopathic medicines, herbal remedies, and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one of them. Your doctor may need to modify your dose and/or take other precautions.

In particular, talk to your doctor or pharmacist if you are taking, have recently taken, or might take 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 Tarbis" and "Be careful with Enalapril/Hydrochlorothiazide Tarbis").
• Antihypertensive medicines (which lower high blood pressure), e.g., vasodilators, beta-blockers, diuretics.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that can increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots).
• Medicines used to treat certain mental disorders, such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics
• 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), e.g., acetylsalicylic acid, including selective cyclooxygenase-2 (COX-2) inhibitors.
• Sympathomimetic medicines (used to treat certain heart and blood vessel disorders and some cold medicines).
• Pressor amines, such as norepinephrine.
• Muscle relaxants, such as tubocurarine.
• Thrombolytic medicines (which prevent blood clots from forming).
• 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 cyclosporine.
• Antibiotics (medicines used to treat certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases, such as rheumatoid arthritis).

Taking Enalapril/Hydrochlorothiazide Tarbis with food, drinks, and alcohol

Enalapril/Hydrochlorothiazide Tarbis can be taken before or after meals.

Alcohol may enhance the blood pressure-lowering effect of enalapril.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

You must tell your doctor if you think you are pregnant (or might be). Your doctor will normally advise you to stop taking Enalapril/Hydrochlorothiazide Tarbis 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 Tarbis. Enalapril/Hydrochlorothiazide Tarbis 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 during this period.

Breastfeeding

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

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

Use in elderly patients

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

Use in athletes

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

Driving and using machines

Enalapril/Hydrochlorothiazide Tarbis 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 notice these effects, you should consult your doctor before performing these activities.

Enalapril/Hydrochlorothiazide Tarbis 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 taking Enalapril/Hydrochlorothiazide Tarbis, as it may alter the test results.

3. How to take Enalapril/Hydrochlorothiazide Tarbis

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

Remember to take your medicine.

Enalapril/Hydrochlorothiazide Tarbis are tablets for oral administration.

You can take the tablets with a glass of water; before, during, or after meals.

The tablets are scored on one side, which allows them to be broken in half. The score line is only to facilitate breaking the tablet if you have difficulty swallowing it whole.

Your doctor will decide the appropriate dose based on your condition and whether you are taking other medicines. The usual dose is one tablet once a day. If necessary, your doctor may increase the dose to two tablets administered once a day.

Symptomatic hypotension may occur after administration of the initial dose of enalapril/hydrochlorothiazide, and this is more likely in patients with volume or salt depletion. If you have taken diuretics before starting treatment, or follow a low-salt diet, your doctor will stop the diuretic 2 or 3 days before starting treatment.

Patient with renal insufficiency or advanced age:Your doctor will indicate the most suitable dose. (See section "Do not take Enalapril/Hydrochlorothiazide Tarbis").

Your doctor will indicate the duration of your treatment with Enalapril/Hydrochlorothiazide Tarbis. Do not stop treatment before or abruptly, as your problem may come back or you may experience other symptoms.

If you think the effect of Enalapril/Hydrochlorothiazide Tarbis is too strong or too weak, tell your doctor or pharmacist.

If you take more Enalapril/Hydrochlorothiazide Tarbis than you should

If you have taken more Enalapril/Hydrochlorothiazide Tarbis than you should, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

It is recommended to take the package 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 Enalapril/Hydrochlorothiazide Tarbis

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

If you stop taking Enalapril/Hydrochlorothiazide Tarbis

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

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.

Adverse effects have been classified taking into account the following frequency definitions: very frequent (may affect more than 1 in 10 patients); frequent (may affect between 1 and 10 in 100 patients); infrequent (may affect between 1 and 10 in 1,000 patients); rare (may affect between 1 and 10 in 10,000 patients); very rare (may affect less than 1 in 10,000 patients); frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders:

infrequent: decrease in red blood cells (oxygen-transporting blood cells).

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

Endocrine disorders:

unknown: syndrome of inadequate antidiuretic hormone secretion (SIADH).

Metabolic and nutritional disorders:

frequent: high blood potassium levels, increased cholesterol, increased triglycerides, increased uric acid in blood; infrequent: low blood glucose and magnesium levels, gout.

rare: increased blood glucose.

very rare: high blood calcium levels.

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.

unknown: 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, heart rhythm disorders, angina pectoris, tachycardia (rapid heartbeats).

infrequent: flushing, palpitations (rapid and irregular heartbeats), myocardial infarction or stroke, possibly secondary to excessive blood pressure reduction in high-risk patients (see section Be especially careful with Enalapril/Hydrochlorothiazide Tarbis).

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 lung alveoli 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).

Skin and subcutaneous tissue disorders:

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 rash with skin and hair loss, skin peeling, appearance of red spots on the skin, skin alteration, skin vesicle formation, Stevens-Johnson syndrome.

A symptomatic complex has been observed that may include some of the following reactions: fever, serositis, vasculitis, muscle inflammation/pain, joint inflammation/pain, positive antinuclear antibody test, increased erythrocyte sedimentation rate, eosinophilia, and leukocytosis. Skin rash, sun sensitivity, or other skin manifestations may also occur.

Musculoskeletal, connective tissue, and bone disorders:

frequent: muscle cramps†.

infrequent: joint pain*.

Renal and urinary disorders:

infrequent: renal dysfunction (kidney function alteration), renal failure, protein presence in urine.

rare: inadequate urine secretion, kidney cell inflammation.

Reproductive system and breast disorders:

infrequent: impotence.

rare: breast enlargement in men.

General disorders and administration site conditions:

very frequent: fatigue.

frequent: chest pain, fatigue.

infrequent: general malaise, fever.

Investigations:

frequent: high blood potassium levels, increased serum creatinine.

infrequent: increased blood urea, low blood sodium levels.

rare: increased liver enzymes, increased serum bilirubin.

Skin and lip cancer (non-melanoma skin cancer):

frequency not known.

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

† The frequency of muscle spasms as "frequent" applies to hydrochlorothiazide doses of 12.5 mg and 25 mg, as found in Enalapril/Hydrochlorothiazide Tarbis, 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 Medicines and Healthcare Products Agency (AEMPS) website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Enalapril/Hydrochlorothiazide

Keep this medicine out of sight and reach of children.

Do not store 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 Tarbis

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

Appearance of the product and package contents

Enalapril/Hydrochlorothiazide Tarbis is presented in the form of oblong tablets, orange in color, and scored on one side. Each package contains 28 tablets.

Marketing authorization holder and manufacturer

Holder:

TARBIS FARMA, S.L.

Gran Vía Carlos III, 94

08028 Barcelona, Spain

Manufacturer:

Laboratorios Medicamentos Internacionales, S.A.

Solana, 26

28850 Torrejón de Ardoz (Madrid), Spain

or

FERRER INTERNACIONAL, S.A.

Joan Buscallá, 1-9

08173 Sant Cugat del Valles (Barcelona), Spain

Date of the last revision of this prospectus:December 2021.

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