MASDIL 300 mg PROLONGED-RELEASE CAPSULES

Introduction

Package Leaflet: Information for the User

MASDIL 300 mg prolonged-release capsules

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 300 mg is and what it is used for.
2. What you need to know before you take MASDIL 300 mg
3. How to take MASDIL 300 mg.
4. Possible side effects.
5. Storage of MASDIL 300 mg

1. Contents of the pack and further information.

1. What Masdil 300 mg is and what it is used for

MASDIL 300 mg belongs to a group of medicines called selective calcium channel blockers with direct cardiac effects, derived from benzothiazepine.

It is indicated for the treatment of angina pectoris and mild to moderate arterial hypertension (elevation of blood pressure). The prolonged-release formulation of MASDIL 300 mg makes it possible for diltiazem to be absorbed in a prolonged manner, allowing for once-daily administration.

2. What you need to know before you take Masdil 300 mg

Do not take MASDIL 300 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, second or third 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 insufficiency with pulmonary congestion.
• If you are being treated with dantrolene (in perfusion).
• If you are already taking a medicine that contains ivabradine used for the treatment of certain heart diseases.
• If you are already taking a medicine that contains lomitapida used for the treatment of high cholesterol levels (see section: "Taking Masdil 300mg with other medicines").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Masdil 300 mg

• If you have heart conditions such as left ventricular insufficiency, bradycardia (slow heart rate), or first-degree atrioventricular block (a type of arrhythmia) 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) along with Masdil 300 mg
• If you are an elderly patient or if you have kidney or liver disease (renal or hepatic insufficiency), the concentrations of diltiazem in the blood may be higher, so your doctor will need to closely monitor your heart rate at the start of treatment.
• In the event of general anesthesia, you should inform the anesthesiologist that you are being treated with this medicine.
• 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. Strict control 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 signs or symptoms of respiratory problems appear 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.

Taking Masdil 300 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 300 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 300 mg").
• Medicines containing lomitapida used for the treatment of high cholesterol levels. Diltiazem may increase the concentration of lomitapida, which can lead to an increased probability and severity of side effects related to the liver.

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

Combinations that require caution:

Medicines for treating cardiovascular problems, such as:

• Alpha blockers, as they increase the hypotensive effect (decrease in blood pressure)
• Beta blockers, as they may cause heart disorders. This combination should only be used if clinically monitored and by electrocardiogram, especially at the beginning of treatment.

• It has been observed that there is an increased risk of depression when diltiazem is administered with beta blockers (see section 4 Possible side effects).

• Amiodarone, digoxin, as they increase the risk of bradycardia. Caution is necessary, 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 they may increase the hypotensive effect and cause fainting.

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

• Cyclosporin (immunosuppressive medicine used in transplants)

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

• Carbamazepine (medicine for treating epilepsy)

• Theophylline (medicine for asthma)

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

• Rifampicin (antibiotic used for treating tuberculosis and some infections) which may 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 for treating mental health problems) as it may increase the toxicity of this. Your doctor will closely monitor your lithium blood levels.

• Colchicine. Masdil 300 mg may lead to an increase in colchicine levels (medicine used for treating gout) when administered concomitantly

• Masdil 300 mg may increase the risk of bleeding if taken with anticoagulants such as direct-acting oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban).

• Masdil 300 mg may cause prolongation of the QT interval (ECG changes, such as changes in heart rate or rhythm, with symptoms of dizziness) when administered with drugs that have the potential or are known to prolong the QT interval.

General information to be taken into account:

• Due to the possible additive effects, caution and assessment 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, and cilostazol) should be considered.

• Medicines metabolized by the CYP3A4 enzyme, as this may 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.

• Patients who consume grapefruit juice should be monitored, as they may 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 those with short action) 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 300 mg is not a suitable medicine for children.

Taking MASDIL 300 mg with food, drinks, and alcohol

The pharmacological effect of MASDIL 300 mg is not altered by the ingestion of food or drinks. Its administration can be done before or during main meals, at any time of the day, but it is recommended to take it always at the same time.

Grapefruit juice should be avoided (see the section "Taking Masdil 300 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 adverse effects reported with the use of Masdil 300 mg, such as dizziness (frequent) and malaise (frequent), the ability to drive and use machines may be altered, although no studies have been conducted on this.

Masdil 300mg contains sodium carmelose

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

3. How to take Masdil 300 mg

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

Remember to take your medicine.

The route of administration of MASDIL 300 mg is oral. The capsule should be swallowed whole, without being opened or chewed.

The dose you need will be determined by your doctor and adjusted individually for you. In general, the recommended doses are as follows:

• Adults: the daily dose, both in angina and hypertension, will be one capsule of MASDIL 300 mg per day, i.e., 300 mg of diltiazem hydrochloride per day.

• Elderly patients: see the section "Warnings and precautions".

• Patients with renal or hepatic insufficiency: should be used with caution. See the section "Warnings and precautions".

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

If you take more MASDIL 300 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 capsules 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 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 undergo gastric lavage and/or osmotic diuresis.

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

If you forget to take MASDIL 300 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 take the next one at the usual time. However, if it is already time for the next dose or is close to it, wait and take it at this time.

If you stop taking MASDIL 300 mg

Your doctor will indicate the duration of your treatment with Masdil 300 mg. Do not stop treatment before.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported according to the frequencies detailed below:

Very common: may affect more than 1 in 10 patients

Common: may affect up to 1 in 10 patients

Uncommon: may affect up to 1 in 100 patients

Rare: may affect up to 1 in 1000 patients

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

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

Blood and lymphatic system disorders:

Frequency not known: thrombocytopenia.

Metabolism and nutrition disorders:

Frequency not known: hyperglycemia.

Psychiatric disorders:

Uncommon:nervousness, difficulty falling asleep (insomnia).

Frequency not known: mood changes including depression.

Nervous system disorders:

Common: headache, dizziness.

Frequency not known: movement disorders (extrapyramidal syndrome).

Cardiac disorders:

Common:atrioventricular block (a type of arrhythmia), palpitations.

Uncommon:slow heart rate (bradycardia).

Frequency not known:sinoatrial block, difficulty of the heart to pump blood (congestive heart failure), cardiac rhythm disorder (sinus arrest), cardiac arrest (asystole).

Vascular disorders:

Common:flushing

Uncommon:drop in blood pressure when standing up quickly, with or without dizziness (orthostatic hypotension).

Frequency not known: vasculitis (diseases that cause inflammation of blood vessels) including leucocytoclastic vasculitis.

Respiratory, thoracic, and mediastinal disorders:

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

Gastrointestinal disorders:

Common: constipation, difficult digestion (dyspepsia), stomach pain, nausea.

Uncommon: vomiting, diarrhea.

Rare:dry mouth.

Frequency not known: inflammation of the hard palate (gingival hyperplasia).

Hepatobiliary disorders:

Uncommon:increase in liver enzyme levels 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), 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), toxic epidermal necrolysis (exfoliative skin disease), sweating, exfoliative dermatitis (cutaneous 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 exfoliative 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 reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for human use medications: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

5. Conservation of Masdil 300 mg

No special conditions are required for conservation.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Keep out of sight and reach of children.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need 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 way, you will help protect the environment.

6. Packaging content and additional information

Composition ofMASDIL 300 mgprolonged-release capsules

• The active ingredient is diltiazem hydrochloride. Each prolonged-release capsule contains 300 mg of diltiazem hydrochloride.
• The other components are: microcrystalline cellulose, acrylic and methacrylic copolymers, ethylcellulose, sodium carmellose, diacetylated monoglycerides, magnesium stearate.

The gelatin capsule is composed of: gelatin, yellow iron oxide (E-172), titanium dioxide (E-171).

Appearance of the product and packaging content

The MASDIL 300 mg capsules are opaque with a white body and a yellow cap, containing a mixture of granules ("pellets"). They are presented in packages with 28 prolonged-release capsules.

Marketing authorization holder and manufacturer

Marketing authorization holder:

EstevePharmaceuticals, 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

Date of the last revision of the prospectus: February 2025

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/