ACEDIUR 20 mg/12.5mg tablets

2. What you need to know before you take Acediur

Do not take ACEDIUR

• If you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6).
• If you have been previously treated with a medicine from the same group of medicines as ACEDIUR (ACE 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 medicine (ask your doctor if you are not sure what sulfonamide-derived medicines are).
• If you do not urinate.
• If you have diabetes or kidney problems and are being treated with a medicine to lower blood pressure that contains aliskiren.
• If you have severe kidney problems.
• If you have been diagnosed with hereditary or idiopathic angioedema (an immune system disorder that causes inflammation in the face and respiratory tract, and abdominal colic).
• If you have severe liver problems.
• If you are pregnant for more than 3 months. It is also recommended to avoid ACEDIUR during the first months of pregnancy (see section on pregnancy).

If you are not sure if you should start taking this medicine, 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 treatment with diuretics (water pills). Inform your doctor if you follow a salt-free diet, take potassium supplements, potassium-sparing medicines or salt substitutes that contain potassium, or if you have recently suffered from vomiting or diarrhea. In these cases, your doctor may need to adjust the dose of ACEDIUR.

• If you have a heart condition that involves narrowing of the heart valves, if you have any blood disorders 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 it is excessively high)

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

• If you are taking any of the following medicines used to treat high blood pressure (hypertension):
• • an angiotensin II receptor antagonist (ARA II) (also known as "sartans" - for example, 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 ACEDIUR.

• If you are using any of the following medicines, the risk of angioedema (rapid swelling under the skin in areas such as the throat) increases:
• • Sirolimus, everolimus and other medicines of the mTOR inhibitor class (used to prevent organ rejection after transplantation).

• 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 an increase in eye pressure and 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 shortness of breath or severe difficulty breathing after taking ACEDIUR, seek medical attention immediately.

Your doctor may monitor your kidney function, blood pressure, and blood 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), 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 medicine.

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

Inform your doctor if you are pregnant (or think you may be). ACEDIUR is not recommended during the first months of pregnancy, and in no case should it be administered if you are pregnant for more than 3 months, as it may harm your baby when administered from that time on (see section on pregnancy).

Use in children

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

Use in elderly patients

In studies where enalapril and hydrochlorothiazide (the active substances of ACEDIUR) 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 ACEDIUR

Inform your doctor or pharmacist if you are using, have recently used or might use any other medicines.

In general, ACEDIUR can be taken with other medicines. However, it is important that you inform your doctor about the other medicines you are taking, as some medicines may affect the action of others.

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 that your doctor knows if you are taking other medicines that lower blood pressure, diuretics (water pills), potassium-containing medicines (including dietary salt substitutes) or lithium (a medicine used to treat a certain type of depression).

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

- Medicines used for pain or inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors.

- Tricyclic antidepressants, antipsychotics.

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

- Gold salts (used to treat rheumatoid arthritis)

- Antidiabetic medicines (both insulin and oral antidiabetics)

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

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

- Corticosteroids.

- Cytostatic medicines (used to treat cancer)

This applies especially if you are also taking:

- Medicines commonly used to prevent organ rejection after transplantation (sirolimus, everolimus and other medicines of the mTOR inhibitor class). See section "Warnings and precautions".

- Potassium supplements or salt substitutes that contain potassium, diuretics (especially potassium-sparing water pills), other medicines that may 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 medicine.

Taking ACEDIUR with food, drinks and alcohol

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

Pregnancy and Breastfeeding

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.

Pregnancy

You should inform your doctor if you are pregnant (or think you may be). Your doctor will generally advise you to stop taking ACEDIUR before you become pregnant or as soon as you know you are pregnant and will recommend that you take another medicine instead of ACEDIUR. ACEDIUR is not recommended during the first months of pregnancy, and in no case should it be administered after the third month of pregnancy, as it may cause serious harm to your baby when administered from that time on.

Breastfeeding

Inform your doctor if you are breastfeeding or are planning to breastfeed. The use of ACEDIUR is not recommended during breastfeeding.

Driving and using machines

Almost all patients can drive, but you should remember that you should not perform tasks that require special attention until you know how you tolerate the medicine (for example, handling hazardous machinery).

Use in athletes:

Athletes are warned that this medicine contains a component that may result in a positive doping test.

ACEDIUR contains lactose and sodium

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

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

3. How to take Acediur

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

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

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 medicine for the time recommended 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 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 Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take ACEDIUR

You should take this medicine as prescribed. Do not take a double dose to make up for forgotten doses. Take the next dose as usual.

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 all people suffer from them.

ACEDIUR is generally well tolerated. The most frequent adverse reactions are dizziness and fatigue. Less frequent ones are: sensation of 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 in such a way that it is difficult to breathe or swallow.
• if your hands, feet, or ankles swell.
• if you develop hives.

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

Very frequent adverse effects (occurring in at least 1 in 10 treated patients):

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

Frequent adverse effects (occurring in at least 1 in 100 and less than 1 in 10 treated patients):

• angioedema (allergic reaction that may involve swelling of the limbs, 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, fainting, alteration of taste
• arrhythmias, angina pectoris, chest pain, tachycardia
• decreased blood pressure, orthostatic hypotension (fainting due to decreased blood pressure)
• dyspnea (difficulty breathing)
• diarrhea, abdominal pain
• skin rash (exanthema)
• muscle cramps
• chest pain, fatigue
• increased creatinine in the blood, increased triglycerides in the blood, increased serum cholesterol

Infrequent adverse effects (occurring in at least 1 in 1,000 and less than 1 in 100 treated patients):

• anemia (including aplastic and hemolytic anemia)
• decreased glucose in the blood, decreased magnesium serum, gout, decreased sodium in the blood, decreased appetite.
• confusion, insomnia, nervousness, decreased libido
• drowsiness, tingling sensation
• vertigo, ringing in the ears
• myocardial infarction, palpitations
• stroke, flushing
• asthma, difficulty breathing, voice disorders, sore throat, and increased nasal secretion
• pancreatitis, peptic ulcer, intestinal obstruction with severe pain, vomiting, digestive disorders, constipation, epigastric discomfort, dry mouth, flatulence
• alopecia (abnormal hair loss), itching, hives, excessive sweating
• joint pain
• kidney function alterations, kidney failure, presence of proteins in urine
• fever, malaise
• increased urea in the blood, low sodium levels in the blood

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

• alterations in blood cell count (abnormally reduced number of neutrophils, 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 glucose in the blood
• abnormal dreams, sleep disorders
• paresis (partial paralysis of movement)
• changes in skin color of hands, feet, nose, or ears (Raynaud's phenomenon)
• respiratory distress (including pneumonia and pulmonary edema) pulmonary infiltrates, 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)
• inflammation and/or ulceration of the oral mucosa, tongue inflammation
• liver failure (liver), liver necrosis (can be fatal), liver inflammation, suppression or cessation of bile secretion (including yellowing of the skin or eyes), inflammation of the gallbladder (particularly in patients with pre-existing gallstone formation in the bile ducts)
• skin peeling, severe blistering or bleeding in the skin (Stevens-Johnson syndrome), blistering of the skin, skin peeling, redness/severe skin rash with skin and hair loss, appearance of red spots on the skin, skin redness
• decreased urine secretion, kidney cell inflammation
• increased breast size in men
• increased liver enzymes, bilirubin in the blood, decreased hemoglobin in the blood, decreased blood cells, increased glucose in the blood

Very rare adverse effects (occurring in less than 1 in 10,000 treated patients):

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

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

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

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

*Only observed in 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 infrequent in patients with a hydrochlorothiazide dose of 6 mg.

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

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 Acediur

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

No special storage conditions are required.

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 down the drain or into the trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, 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 Angileptol mint flavor

Each tablet contains:

• The active ingredients:

Chlorhexidine dihydrochloride, 5 mg

Benzocaine, 4 mg

Enoxolone, 3 mg

• The other components (excipients) are: sorbitol (E420), acesulfame potassium (E950), magnesium stearate, and mint flavor

Appearance of the product and package contents

Angileptol are sucking tablets, white, round, and with the Greek letter σ on one of the faces.

They come in packages containing 15 and 30 sucking tablets.

Other presentations

Angileptol Mint-eucalyptus flavor

Angileptol Honey-lemon flavor

Marketing authorization holder

Alfasigma España S.L.

C/ Aribau 195, 4º

08021 Barcelona, Spain

Manufacturer

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 (Rome), ITALY

Date of the last revision of this prospectus:September 2021

Other sources of information

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