MASDIL RETARD 120 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

Masdil Retard 120 mg prolonged-release tablets

Diltiazem hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What Masdil Retard 120 mg is and what it is used for
2. What you need to know before you take Masdil Retard 120 mg
3. How to take Masdil Retard 120 mg
4. Possible side effects

5 Storage of Masdil Retard 120 mg

1. Contents of the pack and further information

1. What Masdil Retard 120 mg is and what it is used for

Masdil Retard 120mg belongs to a group of medicines called selective calcium channel blockers, which produce dilation of blood vessels, leading to a decrease in blood pressure, as well as an increase in blood flow and a decrease in the heart's oxygen needs.

Masdil Retard 120mg is indicated for:

• prevention and treatment of angina pectoris, including Prinzmetal's angina (vasospastic angina)

treatment of moderate arterial hypertension

2. What you need to know before you take Masdil Retard 120 mg

Do not take Masdil Retard 120 mg:

• if you are allergic to diltiazem hydrochloride or any of the other ingredients of this medicine (listed in section 6).
• if you have any heart rhythm or conduction disorders, such as sick sinus syndrome in patients without a pacemaker, 2nd or 3rd degree atrioventricular block in patients without a pacemaker, or severe bradycardia (heart rate less than 40 beats per minute).
• if you have any cardiac disease such as left ventricular failure with pulmonary congestion.
• if you are being treated with dantrolene (in perfusion).
• if you are already taking a medicine that contains ivabradine used to treat certain heart diseases.
• if you are already taking a medicine that contains lomitapida used to treat high cholesterol levels (see section "Taking Masdil Retard 120 mg with other medicines").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Masdil Retard 120mg

• If you have heart conditions such as ventricular failure, bradycardia (slow heart rate), or first-degree atrioventricular block detected by electrocardiogram, your doctor will need to closely monitor you.
• If you are taking anticoagulants such as direct-acting oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban) with Masdil Retard 120 mg.
• In the event of general anesthesia, you should inform the anesthesiologist that you are being treated with this medicine.
• If you are an elderly patient or have kidney or liver disease (renal or hepatic insufficiency), diltiazem blood levels may be higher, so you will need to be closely monitored.
• If you experience mood changes, including depression, inform your doctor.
• If you are at risk of developing intestinal obstruction, as diltiazem, like other medicines in the same group, can cause a decrease in intestinal movement.
• If you have latent or overt diabetes mellitus. Close monitoring is necessary in these patients due to the possible increase in blood glucose levels.
• The use of diltiazem may induce bronchospasm, including worsening of asthma, especially in patients with pre-existing bronchial hyperreactivity. Cases have also been reported after dose increase. You should inform your doctor if you experience signs or symptoms of respiratory problems during treatment with this medicine.
• If you have a history of heart failure, new difficulty breathing, slow heartbeats, or low blood pressure. Cases of kidney damage have been reported in patients with these conditions, and your doctor may need to monitor your kidney function.

Avoid sun exposure during treatment, as photosensitivity reactions (skin spots) may occur.

Unless your doctor explicitly indicates otherwise, it is not recommended to substitute Masdil Retard 120mg with another medicine that contains diltiazem in a slow-release form.

The active ingredient of Masdil Retard 120mg is inside a tablet that is eliminated whole through the feces.

Taking Masdil Retard 120 mg with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Certain medicines may interact with Masdil Retard 120 mg. In these cases, it may be convenient to change the dose or interrupt treatment with one of the medicines.

In particular, do not take this medicine and inform your doctor if you are taking:

Contraindicated combinations:

• Dantrolene: the simultaneous use of diltiazem with dantrolene (in perfusion) is contraindicated.
• Ivabradina (see section "Do not take Masdil Retard 120 mg").
• Medicines that contain lomitapida used to treat high cholesterol levels. Diltiazem can increase the concentration of lomitapida, which can lead to an increased probability and severity of liver-related side effects.

It is especially important that you inform your doctor if you are taking any of the following medicines:

Combinations that require caution:

Medicines to treat heart problems, such as:

• Alpha blockers, as the hypotensive effect (decrease in blood pressure) is increased
• Beta blockers, as heart disorders may appear. This combination should only be used if clinically monitored and by electrocardiogram, especially at the beginning of treatment.
• A increase in the risk of depression has been observed when diltiazem is administered with beta blockers (see section 4 Possible side effects).

• Amiodarone, digoxin, as the risk of bradycardia is increased. Caution is required, especially in elderly patients and when using high doses.
• Other antiarrhythmic medicines, as diltiazem has antiarrhythmic properties, and there is a risk of increased cardiac side effects. This combination should only be used if clinically monitored and by electrocardiogram.
• Nitrate derivatives, as the hypotensive effect can be increased and fainting can occur.

The combination of diltiazem with the following medicines increases the amount of these medicines in the blood, so your doctor will need to adjust the dose during treatment with diltiazem:

• Ciclosporin (immunosuppressive medicine used in transplants).

• Phenytoin (medicine to treat epilepsy). It is recommended to monitor phenytoin plasma concentrations when administered concomitantly with diltiazem.

• Carbamazepine (medicine to treat epilepsy).

• Theophylline (medicine for asthma).

• H2 antagonists (cimetidine and ranitidine), medicines to treat stomach ulcers, as they produce an increase in the amount of diltiazem in the blood, so either treatment with these medicines will be interrupted, or the daily dose of diltiazem will be adjusted.

• Rifampicin (antibiotic used to treat tuberculosis and some infections), which can produce a decrease in the amount of diltiazem in the blood, so your doctor will closely monitor you.

• X-ray contrast medium: patients treated with diltiazem may experience increased cardiovascular effects, such as hypotension, when administered an intravenous bolus of an ionic X-ray contrast medium. Special caution is required in patients who receive concomitantly diltiazem and an X-ray contrast medium.

• Lithium (medicine to treat mental health problems), as it can increase the toxicity of lithium. Your doctor will closely monitor your lithium blood levels.

• Colchicine. Masdil retard 120 mg can lead to an increase in colchicine levels (medicine used to treat gout) when administered concomitantly.

• Masdil retard 120 mg can increase the risk of bleeding if taken with anticoagulants such as direct-acting oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban).

• Masdil retard 120 mg can cause prolongation of the QT interval (changes in the ECG, such as changes in heart rate or rhythm, with symptoms of dizziness) when administered with drugs that have the potential to prolong the QT interval.

General information to consider:

• Due to the possible additive effects, caution and evaluation are necessary in cases where diltiazem is administered simultaneously with other agents known for their effects on cardiac conduction and/or contractility

• Antiplatelet agents (medicines that prevent blood cells called "platelets" from aggregating and forming a clot): the possibility of an additive effect on platelet aggregation of diltiazem and antiplatelet agents (such as acetylsalicylic acid, ticagrelor, cilostazol) should be considered.

• Medicines metabolized by the CYP3A4 enzyme, as this can result in a decrease in the amount of diltiazem in the blood or an increase in the amount of any of the medicines administered with it.

Patient monitoring is necessary for those consuming grapefruit juice, as it can increase the adverse effects of diltiazem. Grapefruit juice should be avoided if an interaction is suspected.

• Benzodiazepines (midazolam, triazolam), which are medicines with sedative, anxiolytic, anticonvulsant, amnestic, and muscle relaxant effects, as diltiazem increases the amounts of these medicines in the blood, prolonging their stay in the body. Your doctor will be especially careful when prescribing benzodiazepines (especially short-acting ones) if you are taking diltiazem.

• Corticosteroids (methylprednisolone) used as anti-inflammatory and in severe allergies due to their immunosuppressive capacity, as diltiazem reduces the metabolism of methylprednisolone, so your doctor will closely monitor you and adjust the dose of methylprednisolone.

• Statins (medicines used to lower cholesterol), as diltiazem greatly increases the amount of some statins in the blood, which could lead to statin toxicity problems.

• Cilostazol: by inhibiting the metabolism of cilostazol, diltiazem increases its pharmacological activity.

Children and adolescents

Masdil Retard 120 mg is not a suitable medicine for children.

Taking Masdil Retard 120 mg with food, drinks, and alcohol

Masdil Retard 120 mg can be taken at any time of the day, regardless of meals.

Grapefruit juice should be avoided (see the section "Taking Masdil Retard 120 mg with other medicines").

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

This medicine should not be administered to pregnant women or women of childbearing age who are not using an effective contraceptive method.

This medicine should not be taken during breastfeeding, as it passes into breast milk. If the doctor considers it essential to take this medicine, the baby should be fed with an alternative method.

Driving and using machines

Based on the side effects reported with the use of Masdil Retard 120 mg, such as dizziness (frequent) and malaise (frequent), the ability to drive and use machines may be altered, although no studies have been conducted in this regard.

Masdil Retard 120 mg contains polymerized castor oil, sucrose, and sodium.

This medicine can cause stomach upset and diarrhea because it contains polymerized castor oil.

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

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

3. How to take Masdil Retard 120 mg

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

The route of administration of Masdil Retard 120 mg is oral.

Use in adults

The normal dose is 1 tablet every 12 hours (one in the morning and one in the evening).

The Masdil Retard 120 mg tablet should not be chewed, but swallowed whole with the help of a glass of water.

The dose can be taken at any time of the day, before or during meals, but it is recommended to always take your dose at the same time.

Use in elderly and patients with kidney or liver disease

Since in these cases, an increase in diltiazem blood levels may occur, your doctor should consider the need to adjust the dose at the start of treatment.

Patient with renal or hepatic insufficiency:caution is required. See the section "Warnings and precautions".

It is not recommended to substitute diltiazem specialties with each other, unless you receive explicit recommendation from your doctor.

If you take more Masdil Retard 120 mg than you should

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

If you take more tablets than you should, inform your doctor or go immediately to the emergency department of a hospital. Bring the medicine package with you. This is so that the doctor knows what you have taken. The following effects may occur: feeling of dizziness or weakness, blurred vision, chest pain, difficulty breathing, fainting, unusually fast or slow heartbeats, difficulty speaking, confusion, decreased kidney function, coma, and sudden death.

Excess fluid may accumulate in the lungs (pulmonary edema) causing difficulty breathing, which can develop up to 24-48 hours after ingestion.

In case of significant overdose, the patient should be transferred to a specialized center and gastric lavage and/or osmotic diuresis should be performed.

Atropine, adrenaline, glucagon, or calcium gluconate may be administered as antidotes.

If you forget to take Masdil Retard 120 mg

Do not take a double dose to make up for forgotten doses. If you forget to take a dose, take it as soon as you can and the next one at the usual time. However, if it is already time for the next dose or close to it, do not take the missed tablet.

If you stop taking Masdil Retard 120 mg

Your doctor will indicate the duration of your treatment with Masdil Retard 120 mg. Do not stop treatment before. If you stop taking Masdil Retard 120 mg, you may experience a worsening of your disease.

If you have any other 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 following adverse effects have been reported according to the frequencies detailed below:

Very frequent: may affect more than 1 in 10 patients

Frequent: may affect up to 1 in 10 patients

Infrequent: may affect up to 1 in 100 patients

Rare: may affect up to 1 in 1,000 patients

Very rare: may affect up to 1 in 10,000 patients

Frequency not known (cannot be estimated from the available data)

Disorders of the Blood and Lymphatic System:

• Frequency not known:thrombocytopenia.

Disorders of Metabolism and Nutrition:

• Frequency not known:hyperglycemia.

Psychiatric Disorders:

• Infrequent:nervousness, difficulty falling asleep (insomnia).
• Frequency not known:mood changes including depression.

Disorders of the Nervous System:

• Frequent:headache, dizziness.
• Frequency not known:movement disorders (extrapyramidal syndrome).

Cardiac Disorders:

• Frequent:atrioventricular block (a type of arrhythmia), palpitations.
• Infrequent:slow heart rate (bradycardia).
• Frequency not known:sinoatrial block, difficulty of the heart to pump blood (congestive heart failure), cardiac rhythm disease (sinus arrest), cardiac arrest (asystole).

Vascular Disorders:

• Frequent:hot flashes.
• Infrequent:low blood pressure when standing up quickly, with or without dizziness (orthostatic hypotension).
• Frequency not known:vasculitis (diseases characterized by inflammation of blood vessels) including leukocytoclastic vasculitis.

Respiratory, Thoracic, and Mediastinal Disorders:

-Frequency not known: bronchospasm (including worsening of asthma).

Gastrointestinal Disorders:

• Frequent:constipation, difficult digestion (dyspepsia), stomach pain, nausea.
• Infrequent:vomiting, diarrhea.
• Rare:dry mouth.
• Frequency not known:inflammation of the hard palate (gingival hyperplasia).

Hepatobiliary Disorders:

• Infrequent:increased levels of liver enzyme in the blood during the initial treatment period. These elevations are generally transient.
• Frequency not known:hepatitis (inflammatory disease that affects the liver)

Disorders of the Skin and Subcutaneous Tissue:

• Frequent:skin redness (erythema)
• Rare:skin irritation and itching (urticaria)
• Frequency not known:sensitivity to light (photosensitivity), inflammation of the throat, lips, and respiratory tract (angioneurotic edema), rash, erythema multiforme (severe skin disease associated with red spots, blisters), including rare cases of Stevens-Johnson syndrome (severe vesicular reactions of the skin and mucous membranes) and toxic epidermal necrolysis (exfoliative disease of the skin), sweating, exfoliative dermatitis (redness, itching, hair loss), acute generalized exanthematous pustulosis (sudden eruption accompanied by fever, with formation of pustules or lesions on the skin surface characterized by being small, inflamed, filled with pus, and similar to a blister), occasionally erythema with or without fever. Condition in which the body's defense system attacks normal tissue, causing symptoms such as inflamed joints, fatigue, and skin rashes (called "lupus-like syndrome").

Skin rash that may appear on the skin or sores in the mouth (drug-induced lichenoid eruption).

Disorders of the Reproductive System and Breast:

• Frequency not known:excessive breast volume in men (gynecomastia).

General Disorders and Administration Site Conditions:

• Very frequent:edema in the lower limbs.
• Frequent:discomfort.

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 Masdil Retard 120 mg

It does not require special storage conditions.

Keep out of sight and reach of children.

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 away through the sewers or in 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 Masdil Retard 120 mg

• The active ingredient is diltiazem hydrochloride. Each prolonged-release tablet contains 120 mg of diltiazem (as hydrochloride)
• The other components are sodium dihydrogen citrate, sucrose, povidone, magnesium stearate, and macrogol 6000 for the core and sucrose, PVC/PVAc/PVOH copolymer, tributyl acetylcitrate, polymerized castor oil, sodium bicarbonate, ethyl vanillin, and titanium dioxide (E-171) for the coating.

Appearance of the Product and Package Contents

Masdil Retard 120 mg prolonged-release tablets are presented in the form of a coated, circular, biconvex, white tablet in packages containing 60 tablets and 500 tablets (clinical packaging).

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Esteve Pharmaceuticals, S.A.

Passeig de la Zona Franca, 109

08038 Barcelona

Spain

Manufacturer:

TOWA Pharmaceutical Europe, S.L.

c/ de Sant Martí, 75-97

08107 Martorelles (Barcelona)

Spain

or

Meribel Pharma Parets, S.L.U

Ramón y Cajal, 2

08150 Parets del Vallès

Barcelona – Spain

Date of the Last Revision of this Prospectus: February 2025

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/