PATIENT INFORMATION LEAFLET.

HERTEN PLUS 20 mg/12.5 mg FILM-COATED TABLETS

Enalapril/hydrochlorothiazide

Contents of the leaflet:

1. What HERTEN PLUS is and what it is used for.
2. Before taking HERTEN PLUS.
3. How to take HERTEN PLUS.
4. Possible side effects.
5. Storage of HERTEN PLUS.
6. Further information

Herten Plus is a medication with two components: enalapril and hydrochlorothiazide.

Enalapril belongs to a group of medications called angiotensin-converting enzyme inhibitors (ACE inhibitors). It acts by dilating blood vessels, which reduces blood pressure.

Hydrochlorothiazide belongs to a group of medications called thiazide diuretics (medications that increase the elimination of urine).

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

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

Do not take HERTEN PLUS:

• If you are allergic (hypersensitive) to enalapril, hydrochlorothiazide, or any of the other components of this medication.
• If you are allergic to sulfonamide-derived medications. Ask your doctor if you are unsure what sulfonamide-derived medications are.
• If you have previously been treated with a medication from the same group of drugs as HERTEN PLUS (ACE inhibitors) and have had allergic reactions with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing (angioedema).
• 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 airways, and abdominal cramps).
• If you have taken or are currently taking sacubitril/valsartan, a medication used to treat a type of 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 have severe kidney disease. If you have anuria (do not urinate).
• If you have severe liver disease.
• If you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskiren.
• If you are pregnant more than 3 months (second and third trimester of pregnancy) or breastfeeding (see "Pregnancy" and "Breastfeeding"). (It is also best to avoid HERTEN PLUS at the beginning of pregnancy - see Pregnancy section).
• If you have had skin cancer or if a skin lesion appears unexpectedly during treatment. The treatment with hydrochlorothiazide, particularly 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 rays while taking HERTEN PLUS.

If you are unsure whether you should start taking HERTEN PLUS, consult your doctor.

Be especially careful with HERTEN PLUS:

In the following situations, your doctor may need to adjust your HERTEN PLUS dose or monitor your blood potassium levels

• If you have a heart disease that involves narrowing of the heart valves
• (mitral or aortic stenosis) or other factors that reduce blood flow to the left chamber of the heart (hypertrophic obstructive cardiomyopathy).
• If you have conditions that reduce the volume of fluids or the level of sodium in the body (e.g., intense vomiting, diarrhea, or if you are taking high doses of medications that increase urine production).
• If you have blood disorders.
• If you have diabetes, and are taking medications to treat diabetes, including insulin, as it may be necessary to adjust the dose of diabetes medications. Diabetes can cause high levels of potassium in the blood that can be severe.
• If you have liver problems.
• If you have kidney problems (including kidney transplant), as these can cause high levels of potassium in the blood that can be severe.
• If you are undergoing dialysis.
• If you are following a low-sodium diet, taking potassium supplements, potassium-sparing medications (medications that increase potassium levels), or salt substitutes that contain potassium.
• If during treatment you experience an allergic reaction with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing, as well as dizziness; in this case, interrupt treatment and consult your doctor immediately. You should be aware that black patients are more sensitive to this type of reaction to ACE inhibitors.
• If you are taking any of the following medications, the risk of angioedema may increase (rapid swelling under the skin in areas such as the throat):
• Racecadotril (a medication used to treat diarrhea),
• Medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus), Vildagliptin, a medication used to treat diabetes.
• If you are about to undergo a treatment called LDL apheresis, or a desensitization treatment to reduce the effect of an allergy to bee or wasp stings.
• If you have low blood pressure (you may notice it as dizziness or fainting, especially in the initial doses and when standing up. In these cases, lying down may help).
• If you are taking any of the following medications used to treat high blood pressure (hypertension):
• • An angiotensin II receptor antagonist (ARA) (also known as "sartanes" - for example, valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
  • Aliskiren
• If you experience a decrease in vision or eye pain, they may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and may occur within a few hours to a week after taking HERTEN PLUS.
• If you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking Herten plus, seek medical attention immediately.

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

See also the information under the heading "Do not take HERTEN PLUS".

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

Consult your doctor, even if any of the circumstances mentioned above have occurred at any time.

You should inform your doctor if you think you may be pregnant (or could be). HERTEN PLUS is not recommended at the beginning of pregnancy and should not be taken if you are more than 3 months pregnant, as it may cause severe damage to your baby if used in this stage (see Pregnancy section).

Use of other medications:

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription, homeopathic, herbal, and other health-related products, as your doctor may need to adjust your dose and/or take other precautions, or it may be necessary to interrupt treatment with one of them.

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

• An angiotensin II receptor antagonist (ARA) or aliskiren (see also the information under the headings "Do not take Hertén Plus" and "Be especially careful with Hertén Plus")
• Other antihypertensive medications (reduce elevated blood pressure), such as vasodilators, beta-blockers, diuretics.
• Potassium supplements (including salt substitutes),
• Potassium-sparing diuretics and other medications that may increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medication used to prevent blood clots).
• Medications used to treat certain mental disorders such as lithium, antipsychotics, or tricyclic antidepressants.
• Anesthetics.
• Opioids (medications used to treat intense pain).
• Medications used to treat diabetes, such as insulin or oral antidiabetic medications (e.g., metformin).
• Medications used to treat pain or certain inflammation, such as nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, including selective COX-2 inhibitors.
• Sympathomimetics (medications used in the treatment of certain heart and blood vessel disorders and some medications for colds).
• Amines, such as noradrenaline.
• Muscle relaxants, such as tubocurarine.
• Thrombolytic medications (that prevent blood clots).
• Calcium salts and vitamin D.
• Ionic exchange resins (medications used to reduce cholesterol in the blood), such as cholestyramine and colestipol.
• Antiarrhythmics (medications used to prevent and control heart rhythm disorders), such as digitalis glycosides, quinidine, amiodarone.
• Anticholinergic medications (medications that reduce gastric emptying), such as atropine (used before general anesthesia or to prevent spasms) or biperiden (used in patients with Parkinson's disease).
• Medications used to treat gout, such as probenecid, sulfinpyrazone, and allopurinol.
• Antivirals (medications used to treat viral infections), such as amantadine.
• Cytotoxic medications (used to treat cancer), such as cyclophosphamide and methotrexate.
• Immunosuppressants (used to prevent organ transplant rejection), such as cyclosporine.
• Antibiotics (medications used to treat certain infections), such as tetracyclines, amphotericin B.
• Gold salts (used to treat rheumatic diseases such as rheumatoid arthritis).

Taking HERTEN PLUS with food and drinks:

HERTEN PLUScan be taken before or after meals.

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

Pregnancy and Breastfeeding:

Consult your doctor or pharmacist before using a medication.

Pregnancy

You should inform your doctor if you think you may be pregnant (or could be). Normally, your doctor will advise you to stop taking HERTEN PLUS before becoming pregnant or as soon as you know you are pregnant and will advise you to take a different medication instead of HERTEN PLUS. HERTEN PLUS is not recommended at the beginning of pregnancy and should not be taken if you are more than 3 months pregnant, as it may cause severe damage to your baby if used from the third month of pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding or about to start breastfeeding. While taking HERTEN PLUS, it is not recommended to breastfeed newborns (first weeks after birth), and especially premature babies. In the case of an older baby, your doctor should advise you on the benefits and risks of taking HERTEN PLUS compared to other treatments while breastfeeding.

Use in children and adolescents:

The safety and efficacy of HERTEN PLUS have not been established in this population, so it is not recommended for use in children.

Use in elderly patients:

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

Use in athletes

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

Driving and operating machinery:At the beginning of treatment, you may experience symptoms of fatigue and drowsiness or a feeling of instability. It is advisable not to perform tasks that require special attention, such as driving and operating hazardous machinery, until the response to the medication is satisfactory.

Important information about some of the components of HERTEN PLUS:

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

Interference with diagnostic tests

If you need to undergo a diagnostic test to evaluate parathyroid gland function, inform your doctor that you are taking HERTEN PLUS, as it may alter the results.

Follow these instructions unless your doctor has given you different instructions.

Remember to take your medication.

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

Take HERTEN PLUS every day, exactly as instructed by your doctor. It is very important to continue taking this medication for the recommended time by your doctor. Do not take more tablets than the prescribed dose.

The usual dose is one tablet once a day. If necessary, your doctor may increase the dose to two tablets administered once a day.

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.

Patients with altered renal function:

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

Administration Form

This medication is administered orally.

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

HERTEN PLUS can be taken before or after meals

If you take more HERTEN PLUS than you should:

If you have taken more HERTEN PLUS, consult your doctor or pharmacist immediately, or the Toxicological Information Service, Phone: 91-562 04 20, indicating the medication and the amount taken.

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

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

If you forgot to take HERTEN PLUS:

You should take HERTEN PLUS as instructed by your doctor. Do not take a double dose to compensate for the missed doses. Limit yourself to taking the next dose in the usual manner.

If you interrupt treatment with HERTEN PLUS

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

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

Like all medicines, HERTEN PLUS may cause side effects, although not everyone will experience them.

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

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

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

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

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

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

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

Blood and lymphatic system disorders:

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

Rare: reduction of a type of white blood cell (neutrophils), decrease in hemoglobin (protein in red blood cells that carries oxygen), decrease in platelets in the blood, decrease in hematocrit (proportion of red blood cells in the blood), decrease in white blood cells, 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).

Metabolism and nutrition disorders:

Common: high potassium levels in the blood, increased cholesterol, increased triglycerides, increased uric acid in the blood

Uncommon: low glucose and magnesium levels in the blood, gout

Rare: increased glucose levels in the blood

Very rare: high calcium levels in the blood

Nervous system disorders:

Common: headache, dizziness, altered taste

Uncommon: confusion, drowsiness, insomnia, numbness, vertigo

Rare: paralysis (due to low potassium levels).

Mental and behavioural 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 increased 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: hypotension associated with fainting, cardiac rhythm disorders, angina pectoris, tachycardia (rapid heartbeats)

Uncommon: flushing, palpitations (rapid and irregular heartbeats), myocardial infarction or stroke, possibly secondary to excessive hypotension in high-risk patients (see Special precautions when taking HERTEN PLUS)

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

Respiratory, thoracic and mediastinal disorders:

Very common: cough,

Common: shortness of breath

Uncommon: mucus secretion, sore throat, and hoarseness, bronchospasm (difficulty breathing) and asthma

Rare: pulmonary infiltrates, respiratory distress (including pneumonia and pulmonary edema), nasal mucosa inflammation, allergic alveolitis (inflammation of the 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 respiratory distress, fever, weakness, and confusion

Gastrointestinal disorders:

Very common: nausea,

Common: diarrhea, abdominal pain,

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

Rare: mouth and tongue mucosa inflammation

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

Hepatobiliary disorders:

Rare: liver insufficiency, liver necrosis (which can be fatal), liver inflammation, suppression or cessation of bile secretion, yellowing of the skin or eyes, gallbladder inflammation (particularly in patients with pre-existing formation of stones in the bile ducts).

Skin and subcutaneous tissue disorders:

Common: skin rash (exanthema)

Hypersensitivity/angioneurotic edema: facial swelling, extremities, lips, tongue, glottis, and/or larynx

Uncommon: excessive sweating, itching, urticaria, hair loss

Rare: severe skin redness, severe blistering or hemorrhaging in the skin (Stevens-Johnson syndrome), severe skin redness/eruption with skin and hair loss, skin peeling, appearance of red patches on the skin, skin alteration, skin redness, vesicle formation in the skin, Stevens-Johnson syndrome.

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

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

Musculoskeletal, connective tissue and bone disorders:

Common: muscle cramps,

Uncommon: joint pain.

Renal and urinary disorders:

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

Rare: oliguria, renal cell inflammation.

Reproductive and breast disorders:

Uncommon: impotence.

Rare: gynecomastia in men.

General disorders and administration site conditions:

Very common: fatigue.

Common: fatigue, chest pain

Uncommon: general malaise, fever.

Laboratory investigations:

Common: high potassium levels in the blood, increased creatinine levels

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

Rare: increased liver enzymes, increased bilirubin levels in the blood.

Reporting of side effects:

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Do not store at a temperature above 25°C.

Store in the original packaging.

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

Expiration Date:Do not use HERTEN PLUS after the expiration date indicated on the packaging. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medications at the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of HERTEN PLUS:

The active principles 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, cornstarch, pregelatinized cornstarch, magnesium stearate, and yellow iron oxide (E-172).

Appearance of the product and contents of the packaging:

It is presented in the form of tablets. The tablets are yellow, round, and scored on one side. Each package contains 28 or 30 tablets, and the clinical package is 500 tablets.

Holder of the marketing authorization and responsible for manufacturing:

Holder:

INDUSTRIA QUÍMICA Y FARMACÉUTICA VIR, S.A.

C/. Laguna 66-68-70, 28923 ALCORCÓN (Madrid) España

Tel.: 91 486 29 90Fax: 91 486 29 91

Responsible for manufacturing:

INDUSTRIA QUÍMICA Y FARMACÉUTICA VIR, S.A.

C/. Laguna 66-68-70, 28923 ALCORCÓN (Madrid) España

PRESCRIPTION MEDICINE

This prospectus was approved in: January 2022

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