BIMADE 30 mg/10 mg TABLETS

Introduction

Package Leaflet: Information for the User

BIMADE 30 mg/10 mg tablets

delapril hydrochloride + manidipine hydrochloride

Contents of the pack:

1. What is Bimade and what is it used for
2. What you need to know before you take Bimade
3. How to take Bimade
4. Possible side effects
5. Storing Bimade
6. Contents of the pack and other information

1. What is Bimade and what is it used for

Bimade is

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

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

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

The two active substances in Bimade work together to lower blood pressure more effectively than if they were given separately.

Bimade is used for

the treatment of high blood pressure (hypertension) in patients whose blood pressure is not adequately controlled with delapril or manidipine alone.

2. What you need to know before you take Bimade

Do not takeBimade:

• if you are allergic to delapril or any other ACE inhibitor, manidipine or any other calcium channel blocker, or any of the other ingredients of this medicine (listed in section 6)
• if you have previously experienced severe allergic reactions such as swelling of the face, lips, tongue and/or throat with difficulty breathing during previous treatments with ACE inhibitors, or if you or a family member have had these symptoms in any other circumstances
• if you have severe liver disease
• if you have severe kidney problems (e.g. severe kidney disease, are on haemodialysis treatment, have had a kidney transplant or have renal artery stenosis in case you only have one kidney)
• if you have certain heart problems (e.g. have recently had a heart attack or angina pectoris or heart failure)
• if you have aortic stenosis (narrowing of the main blood vessel that comes out of the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle)
• if you have adrenal hyperactivity that may cause low potassium levels in the blood
• if you are pregnant for more than 3 months (it is also best to avoid taking Bimade at the start of pregnancy – see section Pregnancy)
• if you have diabetes or kidney impairment and are being treated with a blood pressure-lowering medicine that contains aliskiren.
• if you have taken or are 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 areas such as the throat) is high
  • • Racecadotril, a medicine used to treat diarrhoea
    • Medicines used to prevent organ rejection and cancer (e.g. temsirolimus, sirolimus, everolimus).
    • Vildagliptin, a medicine used to treat diabetes.

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

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 (e.g. ischaemic cardiopathy)
• if you have blood vessel problems in the brain (cerebrovascular problems)
• if you are going to undergo LDL apheresis (a treatment that removes cholesterol from your blood using a machine)
• if you are going to receive 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 a disease associated with constantly elevated potassium levels in the blood
• if you have signs such as swelling of the face, eyes, lips, tongue, throat or difficulty breathing (see section 4, "Rare side effects")
• if you have abnormal changes in your blood components
• if you are going to undergo anaesthesia or surgery
• if you have a rapid heart rate, dizziness, general weakness that may indicate low blood pressure
• You should consult your doctor if you think you are (or might become) pregnant. Bimade is not recommended at the start of pregnancy, and should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if used after the third month of pregnancy.
• 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), particularly if you have diabetic nephropathy.
• aliskiren
• If you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin in areas such as the throat) is increased:

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

• If you are undergoing peritoneal dialysis.

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 Bimade".

Children and adolescents

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

Taking Bimade with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.

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

• diuretic medicines (used to remove water from the body by increasing the amount of urine) and other medicines to lower blood pressure. These medicines may increase the blood-pressure-lowering effect of Bimade
• heparin (used to prevent blood clots)
• medicines that contain lithium (usually used to treat manic-depressive disorders). These can only be taken with Bimade under close medical supervision
• medicines for pain (e.g. non-steroidal anti-inflammatory drugs, such as aspirin)
• antidepressants, antipsychotics (used to treat schizophrenia and other mental illnesses) and anaesthetics
• medicines that stimulate the sympathetic nervous system (e.g. used for colds)
• potassium-containing salts, potassium-sparing diuretics and other medicines that may increase potassium levels in the blood (e.g. trimethoprim and cotrimoxazole for bacterial infections; ciclosporin, an immunosuppressant used to prevent organ rejection; and heparin, a medicine used to thin the blood to prevent clots).
• digoxin (used to treat heart disorders)
• medicines that affect the blood (e.g. allopurinol, used to treat gout), procainamide (for irregular heartbeats), corticosteroids, immunosuppressants (used to treat autoimmune disorders or prevent organ rejection), medicines for cancer treatment
• medicines for diabetes (oral or insulin)
• vildagliptin, a medicine used to treat diabetes (see also information in the section "Do not take Bimade")
• antacids
• medicines that affect the metabolism of any of the active substances in Bimade, e.g. cimetidine (used to treat stomach ulcers) or certain antibiotics or antifungals (used to treat fungal infections), phenytoin, carbamazepine, phenobarbital, rifampicin, terfenadine and astemizole, class III antiarrhythmic medicines used to normalize heart rate (e.g. amiodarone, quinidine)
• medicines used to treat a type of long-term (chronic) heart failure in adults (e.g. sacubitril/valsartan) (see also information in the section "Do not take Bimade")
• racecadotril, a medicine used to treat diarrhoea (see also information in the section "Do not take Bimade").

Tell your doctor if you are also taking:

• Medicines that are commonly used to prevent organ rejection (sirolimus, everolimus and other medicines belonging to the mTOR inhibitor family). See section "Warnings and precautions"
• Potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that may increase potassium levels in the blood (e.g. trimethoprim and cotrimoxazole for bacterial infections; ciclosporin, an immunosuppressant used to prevent organ rejection; and heparin, a medicine used to thin the blood to prevent clots).

Taking Bimade with food and drink

Bimade should be taken after breakfast.

Do not take grapefruit juice while taking this medicine, as your blood pressure may decrease too much. Drinking alcohol may cause a decrease in blood pressure when standing up.

Avoid salty foods (which contain a lot of sodium chloride), as this may reduce the blood-pressure-lowering effect of Bimade.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Your doctor will normally advise you to stop taking Bimade before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Bimade. Bimade is not recommended at the start of pregnancy, and should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

Bimade is not recommended for mothers who are breast-feeding, and your doctor should choose another treatment if you want to continue breast-feeding, especially if your baby is newborn or was premature.

Driving and using machines

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

Bimade contains lactose and a colouring agent

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

The colouring agent E-110 may cause allergic reactions.

3. How to take Bimade

Follow exactly the administration instructions of Bimade given by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

Recommended dose

The recommended dose of Bimade is one tablet per day.

Dose reduction

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

Administration

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

The tablet can be divided into equal doses.

Duration of treatment

It is important that you continue to take Bimade until your doctor tells you to stop.

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 of age (see section 2, "What you need to know before you take Bimade – Do not take Bimade").

If you take more Bimade than you should

If you have taken more tablets than you should, contact your doctor immediately as this may cause your blood pressure to decrease too much.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately, or go to a hospital or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Bimade

If you forget to take a dose, take the next dose as you normally would. Do not take a double dose to make up for forgotten doses.

If you stop taking Bimade

It is important that you continue to take Bimade until your doctor tells you to stop.

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

4. Possible Adverse Effects

Like all medicines, Bimade can cause adverse effects, although not all people suffer from them.

If adverse effects appear, they are usually mild and transient. However, some adverse effects can be serious and require medical attention.

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

Very frequent	At least 1 in 10 patients
Frequent	At least 1 in 100 patients, but less than 1 in 10 patients
Infrequent	At least 1 in 1,000 patients, but less than 1 in 100 patients
Rare	At least 1 in 10,000 patients, but less than 1 in 1,000 patients
Very rare	Less than 1 in 10,000 patients, including isolated cases
Unknown	Frequency cannot be estimated with available data

Frequent Adverse Effects:

Most frequent adverse effects:

Cough, fluid accumulation in tissues causing edema, headache

Other frequent adverse effects:

Decrease in the number of white blood cells, feeling of apathy, balance disorder, sensation of abnormal movement, sensation of vertigo, dizziness, palpitations, hypotension (especially when standing), hot flashes, bronchitis, nausea, abdominal pain, digestive disorders, fatigue, alteration of analytical parameters (e.g., changes indicating abnormal liver function, increased potassium levels).

Infrequent Adverse Effects:

Anemia due to a lack or insufficient number of new blood cells produced by the bone marrow, significant decrease in the number of white blood cells, which increases the likelihood of infection, decrease in the number of blood platelets, which increases the risk of bleeding or bruising, decrease in the number of certain white blood cells, which increases the likelihood of infection, decrease in blood plasma and red blood cell volume ratio, loss of appetite, confusion, insomnia, mood changes, nervousness, anxiety, irritability, altered taste, blurred vision, increased heart rate, fainting (syncope), breathing difficulties, inflammation of the sinuses and nasal mucosa (e.g., constant nasal secretion), sore throat, vomiting, diarrhea, constipation, dry mouth, formation of stones in the bile ducts (especially if there is inflammation of the gallbladder), redness, itching, skin inflammation with redness and itching (eczema), excessive sweating, muscle and joint stiffness, pain in arms and legs, kidney failure, high protein levels in urine, inability to achieve or maintain an erection (impotence), feeling of weakness, general malaise, alteration of analytical parameters (e.g., changes indicating abnormal liver function).

Rare Adverse Effects:

Allergic reactions, decreased libido, somnolence, myocardial infarction, cardiac rhythm disorders, chest pain due to lack of oxygen to the heart (angina pectoris), chest pain, stroke, stomach pain, hives, abnormal skin redness, muscle cramps, acute kidney failure, accumulation of urea (a waste product excreted in urine) in the blood, irritability, alteration of analytical parameters (e.g., 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 you notice any of these reactions during treatment, stop taking Bimade and inform your doctor immediately.

Very Rare Adverse 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), the frequency, duration, and severity of angina attacks and the occurrence of heart attacks may increase, poor blood circulation causing fingers and toes to become numb and pale (Raynaud's disease), breathing difficulties, pancreatitis, intestinal obstruction, tongue inflammation, appearance of blisters on the face, mouth, eyes, and genitals along with fever (Stevens-Johnson syndrome), hair loss, psoriasis.

Adverse 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)
• Kidney problems: severely decreased urine production (acute kidney injury)
• Muscle pain
• Swelling of the breast with or without pain in men (gynecomastia)
• Cloudy liquid (when performing dialysis through a tube in the abdomen)

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national notification system included in 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 medication.

5. Storage of Bimade

• Keep this medication out of sight and reach of children.
• Do not use this medication after the expiration date indicated on the packaging after "Cad.:".

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and unused medications at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Additional Information

Composition of Bimade

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

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

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

Appearance of the Product and Packaging Content

Bimade is presented in Alu-Alu blisters.

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

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Promedica, S.r.l.

Via Palermo, 26/A

43122 Parma (Italy)

Manufacturer:

Chiesi Farmaceutici, S.p.A.

Via San Leonardo 96

43122 Parma (Italy)

Or

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, Planta 10

08908 L’Hospitalet de Llobregat – Barcelona (Spain)

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

Italy:	Delaman
Spain:	Bimade

Date of the Last Revision of this Prospectus: July 2024

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

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