Package Insert: Information for the User

BIMADE 30 mg/10 mg Tablets

delapril hydrochloride + manidipino hydrochloride

Bimade is

Bimade is an association of two active substances, delapril hydrochloride and manidipino hydrochloride.

Delapril belongs to a group of medications called angiotensin-converting enzyme inhibitors (ACE inhibitors).The angiotensin IIis a substance produced in the body that causes the narrowing of blood vessels.This causes an increase in blood pressure.Delapril hydrochloride prevents the production of angiotensin II, which causes a decrease in blood pressure.

Manidipino belongs to a group of medications called calcium channel blockers, which block the flow of calcium in smooth muscle cells of blood vessels, causing blood vessels to relax with the corresponding reduction in blood pressure.

The two active substances of Bimade work together to decrease blood pressure in a more efficient way than if they were given separately.

Bimade is used for

the treatmentof high blood pressure (hypertension) in patients whose blood pressure is not adequately controlled with delapril or manidipino alone.

Do not takeBimade:

-if you are allergic to delapril or any other angiotensin-converting enzyme (ACE) inhibitor, manidipine or any other calcium channel blocker, or any of the other components of this medication (listed in section 6)

-if you have had severe allergic reactions such as facial, lip, tongue, and/or throat inflammation with difficulty breathing during previous treatments with ACE inhibitors, or if you or a family member has had these symptoms in any other circumstances

-if you have severe liver disease

-if you have severe kidney problems (for example, severe kidney disease, are undergoing hemodialysis (treatment with an artificial kidney), have had a kidney transplant, or have renal artery stenosis (narrowing of the kidney arteries) if you only have one kidney)

-if you have certain heart problems (for example, have recently had a heart attack or angina (chest pain due to inadequate oxygen supply to the heart) or heart failure)

-if you have aortic stenosis (narrowing of the main blood vessel that leaves the heart) or hypertrophic cardiomyopathy (heart muscle disease)

-if you have hyperaldosteronism that may cause low potassium levels in the blood

-if you are more than 3 months pregnant (also it is best to avoid taking Bimade at the beginning of pregnancy – see Pregnancy section)

- if you have diabetes or kidney insufficiency and are being treated with a blood pressure-lowering medication that contains aliskiren.

- 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 are taking any of the following medications, the risk of angioedema may increase:
• • racecadotrilo, a medication used to treat diarrhea
  • medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus)
  • vildagliptina, a medication used to treat diabetes

Do not give Bimade to children or adolescents under 18 years old.

Warnings and precautions:

Consult your doctor or pharmacist before starting to take Bimade:

-if you have kidney problems

-if you have liver problems

-if you have certain heart problems (for example, heart ischemia)

-if you have cerebrovascular problems (blood vessel damage in the brain)

-if you are undergoing LDL apheresis (a procedure that removes cholesterol from the blood using a machine)

-if you are undergoing desensitization treatment to reduce the effects of an allergy to bee or wasp stings

-if you have a connective tissue disease such as systemic lupus erythematosus or scleroderma

-if you are diabetic

-if you have any disease associated with constantly elevated potassium levels in the blood

-if you have symptoms such as facial, eye, lip, tongue, throat inflammation, or difficulty breathing (see section 4, “Rare side effects”)

-if you have abnormal blood components

-if you are undergoing anesthesia or surgery

-if you have rapid heartbeats, dizziness, general weakness that may indicate low blood pressure

-You should consult your doctor if you think you are (or may be) pregnant. Bimade 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 serious damage to your baby if used in this state (see Pregnancy section)

- 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.

- aliskirén

- If you are taking any of the following medications, the risk of angioedema (rapid swelling under the skin in areas such as the throat) is increased:

Sirolimus, everolimus, and other medications belonging to the mTOR inhibitor family (used to prevent organ transplant rejection)

• If you are undergoing peritoneal dialysis.

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

See also the information under the heading “Do not take Bimade”.

Children and adolescents

Do not give Bimade to children or adolescents under 18 years old.

Taking Bimade with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Your doctor may need to modify your dose and/or take other precautions if you are taking any of the following medications:

-diuretics (used to eliminate water from the body by increasing urine production) and other medications to lower blood pressure. These medications may potentiate the hypotensive effect of Bimade

-heparin (used to prevent blood clots)

-medications containing lithium (usually used to treat manic-depressive disorders). These can only be taken with Bimade under close supervision by your doctor

-pain medications (e.g., nonsteroidal anti-inflammatory drugs, such as aspirin)

-antidepressants, antipsychotics (used to treat schizophrenia and other mental disorders) and anesthetics

-medications that stimulate the sympathetic nervous system (e.g., used for colds)

-sodium-containing medications or potassium-sparing diuretics. In this case, special precautions should be taken (e.g., blood tests)

-digoxin (used to treat heart disorders)

-medications that alter blood components (e.g., alopurinol, used to treat gout), procainamide (for irregular heartbeats), corticosteroids, immunosuppressants (used to treat autoimmune disorders or to prevent rejection after organ transplantation), cancer medications

-diabetes medications (oral medications or insulin)

-vildagliptina, a medication used to treat diabetes (see also information in the section “Do not take Bimade”)

-antacids

-medications that alter the metabolism of some of the active substances in Bimade, for example, cimetidine (used to treat stomach ulcers) or certain antibiotics or antifungals (used to treat fungal infections), phenytoin, carbamazepine, phenobarbital, rifampicin, terfenadine, and astemizol, antiarrhythmics of class III used to normalize heart rate (e.g., amiodarone, quinidine)

-if you are taking an angiotensin II receptor antagonist (ARA) or aliskirén (see also information under the headings “Do not take Bimade” and “Warnings and precautions”)

-medications used to treat a type of chronic heart failure in adults (e.g., sacubitril/valsartan) (see also information in the section “Do not take Bimade”)

-racecadotrilo, a medication used to treat diarrhea (see also information in the section “Do not take Bimade”).

Inform your doctor if you are also taking:

• Medications used to prevent organ transplant rejection (sirolimus, everolimus, and other medications belonging to the mTOR inhibitor family). See section “Warnings and precautions”
• Supplements of potassium (including salt substitutes), potassium-sparing diuretics, and other medications that may increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medication used to dilute the blood to prevent clots).

Taking Bimade with food and drinks

Bimade should be taken after breakfast.

Do not take orange juice while taking this medication, as your blood pressure may drop too low. Drinking alcohol may cause a drop in blood pressure when standing.

Avoid salty foods (containing a large amount of sodium chloride), as it may reduce the hypotensive effect of Bimade.

Pregnancy and breastfeeding

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

Pregnancy

Your doctor will usually advise you to stop taking Bimade before becoming pregnant or as soon as you know you are pregnant and advise you to take another medication instead of Bimade. Bimade 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 serious damage to your baby if used after the third month of pregnancy.

Breastfeeding

Bimade is not recommended for mothers who are breastfeeding, and your doctor should choose another treatment if you wish to continue breastfeeding, especially if your baby is newborn or premature.

Driving and operating machinery

It is unlikely that Bimade will affect your ability to drive or operate machinery. However, occasionally it may cause dizziness due to low blood pressure. If this happens, you should consult your doctor before attempting these activities.

Bimade contains lactose and a coloring agent

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

The E-110 coloring agent may cause allergic reactions.

Follow exactly the administration instructions for Bimade as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose of Bimade is one tablet per day.

Dose reduction

If you are over 65 years old or if you have kidney or liver disease, your doctor may prescribe a lower dose.

Administration

Bimade should be taken in the morning after breakfast. The tablet should be swallowed whole with enough water. You should try to take your daily dose approximately at the same time each day.

The tablet can be divided into equal doses.

Treatment duration

It is essential that you continue taking Bimade until your doctor tells you otherwise.

Please take the exact dose prescribed by your doctor and do not change it without consulting him first.

Use in children and adolescents

Do not give Bimade to children or adolescents under 18 years old (see section 2, “What you need to know before starting to take Bimade – Do not take Bimade”).

If you take more Bimade than you should

If for any reason you have taken more tablets than you should, consult your doctor immediately as it may cause your blood pressure to drop too low.

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

If you forget to take Bimade

In case you forget to take a dose, take the next dose as you normally do. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Bimade

It is essential that you continue taking Bimade until your doctor tells you otherwise.

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

Like all medicines, Bimade can cause side effects, although not everyone will experience them.

If side effects occur, they are usually mild and temporary. However, some side effects can be serious and require medical attention.

The frequency of side effects is classified into the following categories:

Common side effects:

Common side effects:

Cough, accumulation of fluid in tissues causing edema, headache

Other common side effects:

Decreased white blood cell count,feeling ofapathy, balance disorder, abnormal sensation of movement, sensation of dizziness, dizziness, palpitations, hypotension (especially when standing), hot flashes, bronchitis, nausea, abdominal pain, digestive disorders, fatigue, alteration of analytical parameters (for example, changes indicating abnormal liver function, increased potassium levels).

Uncommon side effects:

Anemia due to a lack or insufficient number of new blood cells produced by the bone marrow, severe decrease in white blood cell count that increases the risk of infections, decrease in platelet count that increases the risk of bleeding or hematomas, decrease in certain white blood cell count that increases the risk of infections, decrease in plasma blood volume and red blood cell volume ratio, loss of appetite, confusion, insomnia, mood changes, nervousness, anxiety, feeling of irritability, altered taste, blurred vision, increased heart rate, fainting (syncope), respiratory difficulty, inflammation of the breasts and nasal mucosa (for example, constant nasal secretion), sore throat, vomiting, diarrhea, constipation, dry mouth, formation of gallstones in the bile ducts (especially if there is inflammation of the gallbladder), redness, itching, skin inflammation with redness and itching (eczema), excessive sweating, muscle stiffness and joint stiffness, pain in the arms and legs, renal insufficiency, high protein levels in the urine, inability to achieve or maintain an erection (impotence), feeling of weakness, general discomfort, alterations of analytical parameters (for example, changes indicating abnormal liver function).

Rare side effects:

Allergic reactions, decreased libido, somnolence, myocardial infarction, cardiac arrhythmias, chest pain due to lack of oxygen to the heart (angina pectoris), chest pain, stroke, stomach pain, urticaria, abnormal skin redness, muscle cramps, acute renal insufficiency, urea accumulation (a waste product excreted in the urine) in the blood, irritability, alterations of analytical parameters (for example, increased bilirubin, changes indicating abnormal heart or muscle function).

Rare reactions that may be caused by these types of medications include inflammation of the face, lips, tongue, throat, or difficulty breathing. If during treatment you notice any of these reactions,stop taking Bimade and inform your doctor immediately.

Very rare side effects (including isolated cases):

Anemia due to rapid destruction of red blood cells, in patients with pre-existing angina pectoris (chest pain due to lack of oxygen to the heart) may increase the frequency, duration, and severity of angina attacks and the occurrence of heart attacks, poor blood circulation that makes the fingers and toes numb and pale (Raynaud's disease), respiratory difficulty, pancreatitis, intestinal obstruction, inflammation of the tongue, appearance of blisters on the face, mouth, eyes, and genitals with fever (Stevens-Johnson syndrome), hair loss, psoriasis.

Side effects of unknown frequency:

• High potassium levels in the blood (hyperkalemia)
• Swelling of the skin, lips, tongue, or throat with difficulty swallowing or breathing (angioedema)
• Renal problems: severely decreased urine output (acute renal failure)
• Muscle pain
• Swelling of the breast with or without pain in men (gynecomastia)
• Cloudy fluid (when performing dialysis through a tube in the abdomen.

Reporting 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 national notification system included in the Spanish System of Pharmacovigilance of Medicines for Human Usehttps://www.notificaram.es.

By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

- Do not use this medication after the expiration date indicated on the packaging after “Cad.:”.

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

Composition of Bimade

Bimade is a combination of two active substances, delapril hydrochloride and manidipino hydrochloride.

Each Bimade 30 mg/10 mg tablet contains 30 mg of delapril hydrochloride and 10 mg of manidipino hydrochloride respectively.

The other components are lactose monohydrate, partially substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate, riboflavin, andaluminum lake E-110 (orange-yellow).

Appearance of the product and contents of the package

Bimade is presented in Alu-Alu blisters.

Each package of Bimade contains 28 rounded, scored, salmon-colored tablets.

Holder of the marketing authorization and responsible manufacturer

Holder of the marketing authorization:

Promedica, S.r.l.

Vía Palermo, 26/A

43122 Parma (Italy)

Manufacturer:

Chiesi Farmaceutici, S.p.A.

Vía San Leonardo 96

43122 Parma (Italy)

Ó

Fine Foods & Pharmaceuticals N.T.M. S.p.A.

Via Grignano, 43

24041 Brembate (BG)

Italy

Local representative:

Chiesi España, S.A.U.

Plaça d’Europa, 41-43, 10th floor

08908 L’Hospitalet de Llobregat – Barcelona (Spain)

This medicine is authorized in the following Member States of the EEA under the following names:

Last review date of this leaflet: July 2024

Delapril and manidipino are licensed from Takeda Pharmaceutical Company, Ltd.

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