CO-RENITEC 20 mg/12.5 mg TABLETS

2. What you need to know before you take Co-Renitec

Do not take Co-Renitec

• 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 of medicines as Co-Renitec (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 Co-Renitec at the start of pregnancy - see section on 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 Co-Renitec, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Co-Renitec.

In the following situations, your doctor may need to adjust your dose of Co-Renitec or monitor your blood potassium levels:

• 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 Co-Renitec, seek medical attention immediately.
• If you have a heart disease that involves narrowing of the heart valves (mitral or aortic stenosis) or other factors that reduce left ventricular outflow (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 other medicines that can increase potassium levels in the blood, such as heparin (a medicine used to prevent blood clots), trimethoprim, or cotrimoxazole (also known as trimethoprim/sulfamethoxazole, medicines used to treat bacterial infections).
• If an allergic reaction with swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing occurs 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 a bee or wasp sting allergy.
• If you have low blood pressure, as the use of Co-Renitec, 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 Co-Renitec 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 and UV ray exposure while taking Co-Renitec.

• 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 diabetic kidney problems.
  • aliskiren

• Tell your doctor if you experience a decrease in vision or eye pain, as these may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, which can occur within hours to weeks after taking Co-Renitec. 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 Co-Renitec".

Before undergoing surgery or anesthesia (even at the dentist), inform your doctor or dentist that you are taking Co-Renitec, 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). Co-Renitec is not recommended at the start of pregnancy and must 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 on pregnancy).

Children and adolescents

The safety and efficacy of Co-Renitec 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 Co-Renitec

Tell your doctor or pharmacist if you are taking, have recently taken, or might take 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 Co-Renitec" and "Warnings and precautions")
• Blood pressure-lowering medicines (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; cyclosporin, an immunosuppressant 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), like 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 noradrenaline.
• Muscle relaxants, such as tubocurarine.
• Thrombolytic medicines (used to prevent blood clots).
• 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 (used to decrease 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.
• Immunosuppressant 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 Co-Renitec" and "Warnings and precautions".

Taking Co-Renitec with food and drink

Co-Renitec can be taken with or without food. Most people take Co-Renitec 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 plan to become pregnant, consult your doctor before using this medicine. Normally, your doctor will advise you to stop taking Co-Renitec before becoming pregnant or as soon as you know you are pregnant and will advise you to take a different medicine instead of Co-Renitec. Co-Renitec is not recommended during pregnancy and must 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. Co-Renitec is not recommended in breastfeeding mothers.

The two active substances of Co-Renitec, enalapril and hydrochlorothiazide, pass into breast milk. If you are breastfeeding or plan to breastfeed, consult your doctor.

Driving and using machines

Co-Renitec 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.

Co-Renitec 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.

Co-Renitec contains sodium

This medicine contains less than 23 mg of sodium (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 Co-Renitec, as it may alter the test results.

3. How to take Co-Renitec

Follow the instructions for administration of this medicine exactly as prescribed 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 right dose for you, depending on your condition and whether you are taking other medicines.

Take Co-Renitec every day, exactly as indicated by your doctor. It is very important that you continue taking this medicine for the time your doctor prescribes it. Do not take more tablets than the prescribed dose.

The recommended dose is one or two tablets administered once a day. Take Co-Renitec every day, exactly as indicated by your doctor. It is very important that you continue taking this medicine for the time your doctor prescribes it. 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 for you.

Method of administration

This medicine is administered orally.

Take the Co-Renitec tablets with the help of a glass of water.

Co-Renitec can be taken before or after meals.

If you take more Co-Renitec than you should

If you have taken more Co-Renitec 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 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 Co-Renitec

You should take Co-Renitec as prescribed. Do not take a double dose to make up for forgotten doses. Just take the next dose as usual.

If you stop taking Co-Renitec

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

Do not stop taking your medicine unless your doctor tells you to do so.

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.

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)

Uncommon: (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 the 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:

Uncommon: decrease in red blood cells (oxygen-carrying blood cells)

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 disorders.

Endocrine disorders:

Frequency not known: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolic and nutritional disorders:

Frequent: low 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:

Frequent: headache, syncope, altered taste

Uncommon: confusion, somnolence, insomnia, tingling sensation, vertigo

Rare: paralysis (due to low potassium levels in the blood).

Psychiatric disorders:

Frequent: depression

Uncommon: nervousness, decreased libido*

Rare: abnormal dreams, sleep disorders.

Eye disorders:

Very frequent: blurred vision

Frequency not known: 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:

Uncommon: ringing in the ears.

Cardiac and vascular disorders:

Very frequent: dizziness

Frequent: low blood pressure associated with fainting, cardiac rhythm disorders, chest pain, tachycardia (rapid heart rate)

Uncommon: flushing, palpitations (rapid and irregular heartbeat), 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: shortness of breath

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

Rare: pulmonary infiltrates, respiratory difficulty (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 difficulty (signs include severe respiratory difficulty, fever, weakness, and confusion).

Gastrointestinal disorders:

Very frequent: nausea

Frequent: diarrhea, abdominal pain

Uncommon: 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 oral 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 stones).

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

Uncommon: 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 redness, blistering on the skin.

A symptomatic complex has been reported that may include all or 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 †

Uncommon: joint pain *

Renal and urinary disorders:

Uncommon: renal dysfunction (alteration of kidney function), renal failure, presence of proteins in the urine

Rare: inadequate urine secretion, inflammation of kidney cells.

Reproductive system and breast disorders:

Uncommon: impotence

Rare: breast enlargement in men.

General disorders and administration site conditions:

Very frequent: fatigue

Frequent: chest pain, fatigue

Uncommon: general malaise, fever.

Investigations:

Frequent: high potassium levels in the blood, increased serum creatinine

Uncommon: 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 Co-Renitec.

† The frequency of muscle cramps as "frequent" applies to hydrochlorothiazide doses of 12.5 mg and 25 mg, as found in Co-Renitec, although the frequency of the event is "uncommon", and applies to the 6 mg hydrochlorothiazide dose as in Renitecmax.

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. Conservation of Co-Renitec

Keep this medicine out of sight and reach of children.

Do not store above 25 °C.

Store in the original packaging.

Do not use this medicine after the expiration date that appears on the box 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 containers 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 containers and medicines you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Co-Renitec

• The active ingredients are enalapril 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, corn starch, pregelatinized corn starch, magnesium stearate, and yellow iron oxide (E-172).

Appearance of the product and package contents

It is presented in packages of 28 scored tablets. The tablets are biconvex, hexagonal, yellow, scored, and marked with "MSD 718" on one face.

The score line is only for breaking the tablet and facilitating swallowing, but not for dividing into equal doses.

Marketing authorization holder and manufacturer

Date of the last revision of this prospectus:06/2022.

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