Package Insert: Information for the User

ACEDIUR 20 mg/12.5 mg Tablets

enalapril maleate/hydrochlorothiazide

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.

If you have any questions, consult your doctor or pharmacist.

• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is Acediur and how it is used

2. What you need to know before starting to take Acediur

3. How to take Acediur

4. Possible adverse effects

5. Storage of Acediur

6. Contents of the package and additional information

Acediur is a medication that contains two active ingredients: enalapril maleate and hydrochlorothiazide.

The enalapril component of Acediur is an active ingredient that belongs to a group of drugs called angiotensin-converting enzyme inhibitors (ACE inhibitors). The hydrochlorothiazide component of Acediur is an active ingredient that belongs to a group of drugs called diuretics (which stimulate urination). Together, enalapril and hydrochlorothiazide help to lower elevated blood pressure.

Your doctor has prescribed Acediur to treat hypertension (high blood pressure).

Do not take ACEDIUR

• If you are allergic to the active ingredients or any of the other components of this medication (listed in section 6).
• If you have previously been treated with a medication from the same group of drugs as ACEDIUR (angiotensin-converting enzyme inhibitors) and have had allergic reactions such as swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing.
• If you are allergic to any sulfonamide-derived medication (ask your doctor if you are unsure what sulfonamide-derived medications are).
• If you are unable to urinate.
• If you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskiren.
• If you have severe kidney insufficiency.
• 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 cramps).
• If you have severe liver insufficiency.
• If you are more than 3 months pregnant. It is also recommended to avoid ACEDIUR during the first months of pregnancy (see section pregnancy).

If you are unsure whether you should start taking this medication, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take ACEDIUR.

• If you have had liver, kidney, or diabetes problems, if you are undergoing dialysis, or if you are receiving diuretic treatment (tablets to urinate). Inform your doctor if you are following a low-sodium diet, taking potassium supplements, potassium-sparing medications, or salt substitutes containing potassium, or if you have recently had vomiting or diarrhea. In these cases, your doctor may need to adjust the dose of ACEDIUR.

• If you have a heart disease that is associated with narrowing of the heart valves, if you have any blood abnormalities or detect any signs of infection.

• If you are about to undergo LDL-apheresis treatment (a procedure to remove LDL particles from the blood when they are excessively elevated).

• If you detect signs of fluid or electrolyte imbalance, such as thirst, dry mouth, weakness, numbness, drowsiness, agitation, pain or cramps, muscle fatigue, decreased blood pressure, decreased urine production, tachycardia, nausea, and/or vomiting.

• If you are taking any of the following medications used to treat high blood pressure (hypertension):
• • An angiotensin II receptor antagonist (ARA II) (also known as "sartans" - for example, valsartan, telmisartan, irbesartan), particularly 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. The 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 exposure to sunlight and ultraviolet (UV) rays while taking ACEDIUR.

• If you are taking any of the following medications, the risk of angioedema (rapid swelling under the skin in areas such as the throat) increases:
• • Sirolimus, everolimus, and other mTOR inhibitors (used to prevent organ transplant rejection).

• If you experience a decrease in vision or eye pain, it may be a symptom of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which can occur within a few hours to a week after taking ACEDIUR.
• 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 ACEDIUR, seek medical attention immediately.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (such as potassium) at regular intervals.

See also the information under the heading "Do not take ACEDIUR".

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

If you have any doubts about any of these aspects, consult your doctor or pharmacist before taking this medication.

Your skin becomes more sensitive to sunlight or ultraviolet (UV) rays while taking ACEDIUR. Avoid exposure to intense sunlight or artificial ultraviolet (UV) light, such as tanning beds.

Inform your doctor if you are pregnant (or if you suspect you may be). It is not recommended to use ACEDIUR at the beginning of pregnancy, and in any case, it should not be administered after the third month of pregnancy, as it may cause harm to your baby when administered from that point on (see section: Pregnancy).

Use in children

The safety and efficacy of this medication have not been established in children.

Use in elderly patients

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

Other medications and ACEDIUR

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

ACEDIUR can usually be taken with other medications. However, it is essential to inform your doctor of any other medications you are taking, as some medications may interact with each other.

Your doctor may need to adjust your dose and/or take other precautions:

If you are taking an angiotensin II receptor antagonist (ARA II) or aliskiren (see also the information under the headings "Do not take ACEDIUR" and "Warnings and precautions").

To prescribe the correct dose of ACEDIUR, it is especially important for your doctor to know if you are taking other medications that lower blood pressure, diuretics (urine tablets), potassium medications (including salt substitutes), or lithium (a medication used to treat certain types of depression).

Inform your doctor if you are taking any of the following medications:

-Pain or anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors.

-Tricyclic antidepressants, antipsychotics.

-Sympathomimetic medications (used to treat certain heart and blood vessel disorders).

-Gold salts (used to treat rheumatoid arthritis).

-Antidiabetic medications (both insulin and oral antidiabetic medications).

-Ion exchange resins (medications used to reduce cholesterol in the blood) such as cholestyramine and colestipol.

-Antiarrhythmic medications (used to control heart rhythm abnormalities) such as quinidine, procainamide, amiodarone, sotalol, and digitalis glycosides.

-Corticosteroids.

-Cytostatic medications (used to treat cancer).

This applies especially if you are also taking:

-Medications used more frequently to prevent organ transplant rejection (sirolimus, everolimus, and other mTOR inhibitors). See section "Warnings and precautions".

-Potassium supplements or salt substitutes containing potassium, diuretics (urine tablets, especially those called potassium-sparing diuretics), other medications that can increase potassium levels in the body (such as heparin and cotrimoxazole, also known as trimethoprim/sulfamethoxazole).

If you have any doubts about the above, consult your doctor or pharmacist before taking this medication.

Taking ACEDIUR with food, drinks, and alcohol

Alcohol may increase the blood pressure-lowering effect of this medication. See section: "How to take Acediur".

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you suspect you may be pregnant, consult your doctor before using this medication.

Pregnancy

You should inform your doctor if you are pregnant (or if you suspect you may be). Your doctor will usually recommend that you stop taking ACEDIUR before becoming pregnant or as soon as you know you are pregnant and recommend that you take another medication instead of ACEDIUR. It is not recommended to use ACEDIUR at the beginning of pregnancy, and in any case, it should not be administered after the third month of pregnancy, as it may cause harm to your baby when administered from that point on.

Breastfeeding

Inform your doctor if you are breastfeeding or plan to start breastfeeding. It is not recommended to use ACEDIUR during breastfeeding.

Driving and operating machinery

Most patients can drive, but you should remember that you should not perform tasks that require special attention until you know how you tolerate the medication (for example, operating hazardous machinery).

Use in athletes:

Warning to athletes: This medication contains a component that may result in a positive analytical result for doping control.

ACEDIUR contains lactose and sodium

This medication contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

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

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

ACEDIUR tablets are taken orally. Tablets can be taken before or after meals, with a glass of water.

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

The usual dose is one tablet once a day.

Take ACEDIUR every day, exactly as indicated 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.

If you take more ACEDIUR than you should

The most likely symptoms would be 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.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take ACEDIUR

You should take this medication as prescribed. Do not take a double dose to compensate for the missed doses. Take the next dose in the usual manner.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

ACEDIUR is generally well tolerated. The most common side effects are dizziness and fatigue. Less common ones are: dizziness or vertigo when standing up quickly (due to a drop in blood pressure), muscle cramps, nausea, weakness, headaches, cough, and impotence.

Stop taking ACEDIUR and consult your doctor immediately in any of the following cases:

• if your face, lips, tongue, and/or throat swell up, making it difficult to breathe or swallow.
• if your hands, feet, or ankles swell up.
• if you develop urticaria.

The side effects reported for enalapril-hydrochlorothiazide administered in combination are detailed below according to the following frequencies:

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

• blurred vision
• dizziness
• cough
• nausea
• erectile dysfunction
• fatigue

Common side effects (occur in at least 1 in 100 and fewer than 1 in 10 patients treated):

• angioedema (allergic reaction that may be accompanied by swelling of the extremities, lips, tongue, and/or throat), hypersensitivity (allergic reaction)
• decreased potassium levels in the blood, increased cholesterol in the blood, increased triglycerides in the blood, increased uric acid levels in the blood
• depression
• headache, dizziness, altered taste
• arrhythmias, angina pectoris, chest pain, tachycardia
• decreased blood pressure, orthostatic hypotension (dizziness due to decreased blood pressure)
• shortness of breath
• diarrhea, abdominal pain
• skin rash (exanthema)
• muscle cramps
• chest pain, fatigue
• increased creatinine in the blood, increased triglycerides in the blood, increased serum cholesterol

Rare side effects (occur in at least 1 in 1,000 and fewer than 1 in 100 patients treated):

• anemia (including aplastic and hemolytic anemia)
• decreased glucose levels in the blood, decreased serum magnesium, gout*, decreased sodium levels in the blood, decreased appetite
• confusion, insomnia, nervousness, decreased libido*
• drowsiness, tingling sensation
• vertigo, ear noise
• myocardial infarction, palpitations
• stroke, shortness of breath
• asthma, difficulty breathing, voice disorders, throat pain, and increased nasal secretion
• pancreatitis, peptic ulcer, intestinal obstruction with severe pain, vomiting, digestive discomfort, constipation, epigastric discomfort, dry mouth, flatulence (gas)*
• alopecia (abnormal hair loss), itching, urticaria, excessive sweating
• joint pain
• kidney function alterations, renal insufficiency, proteinuria in the urine
• fever, malaise
• increased urea levels in the blood, decreased sodium levels in the blood

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

• blood cell count alterations (abnormally reduced neutrophil count, decreased platelet count, decreased white blood cell count), bone marrow depression (decreased ability of the body to form blood cells), lymph node inflammation
• autoimmune disorder
• increased blood glucose levels
• abnormal dreams, sleep disorders
• partial paralysis (paresis)
• changes in skin color on hands, feet, nose, or ears (Raynaud's phenomenon)
• respiratory distress (including pneumonia and pulmonary edema), pulmonary infiltrates, nasal mucosa inflammation, 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)
• oral mucosa inflammation and/or ulceration, tongue inflammation
• liver insufficiency (liver), liver necrosis (may be fatal), liver inflammation, bile secretion suppression (including yellow skin or eye discoloration), gallbladder inflammation (particularly in patients with pre-existing gallstone formation)
• skin peeling, severe blistering or hemorrhaging on the skin (Stevens-Johnson syndrome), skin vesicles, skin peeling,severe skin redness/eruption with skin and hair loss, appearance of red spots on the skin, skin redness
• decreased urine secretion, kidney cell inflammation
• breast enlargement in men
• increased liver enzymes, increased bilirubin in the blood, decreased hemoglobin in the blood, decreased blood cells, increased blood glucose levels

Very rare side effects (occur in fewer than 1 in 10,000 patients treated):

• increased calcium levels in the blood
• intestinal inflammation
• Acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion).

Side effects of unknown frequency (cannot be estimated from available data):

• skin cancer and lip cancer (non-melanoma skin cancer)
• confusion, nausea, and irritability due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• 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]

A complex symptom syndrome has been reported that may include fever, serositis, vasculitis, muscle inflammation/pain, joint inflammation/pain, positive antinuclear antibodies, increased sedimentation rate, eosinophilia, and leukocytosis. Skin rash, sensitivity to sunlight, or other skin manifestations may also occur.

*Only observed at hydrochlorothiazide doses of 12.5 mg and 25 mg

¥The frequency of frequent muscle cramps belongs to hydrochlorothiazide doses of 12.5 mg and 25 mg, while the frequency of the event is rare in patients with 6 mg hydrochlorothiazide doses.

Other rare side effects may also occur, some of which may be severe. Ask your doctor or pharmacist for more information about side effects. Both have a more complete list of them.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the 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.

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

No special storage conditions are required.

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

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of ACEDIUR

• The active principles are: 20 mg of enalapril maleate and 12.5 mg of hydrochlorothiazide.
• The other components (excipients) are: lactose, sodium bicarbonate, cornstarch, pregelatinized cornstarch, magnesium stearate, and yellow iron oxide (E-172).

Appearance of the product and contents of the packaging

ACEDIUR 20 mg/12.5 mg are yellow, round, flat, scored tablets on one side. They are presented in blisters in packaging of 30 tablets or 500 tablets (clinical packaging).

Holder of the marketing authorization

Alfasigma España S.L.

Av. Diagonal, 490

08006 Barcelona. SPAIN

Responsible for manufacturing

Pharmaloop, S.L.

Polígono Industrial Azque C/Bolivia, 15

28806 Alcalá de Henares (Madrid). SPAIN

Or

Alfasigma, S.p.A.

Via Pontina Km 30,400

00071 – Pomezia (Roma). ITALY

Last review date of this leaflet: December 2021

Other sources of information

“Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)https://www.aemps.gob.es”