Masdil 300 mg prolonged-release capsules

Patient Information Leaflet

Introduction

Patient Information Leaflet

MASDIL 300 mg prolonged-release capsules

Hydrochloride diltiazem

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you and should not be given to others, even if they have the same symptoms, as it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet Contents

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

2. What you need to know before taking MASDIL 300 mg.

3. How to take MASDIL 300 mg.

4. Possible adverse effects.

5. How to store MASDIL 300 mg.

6. Contents of the pack and other 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 (elevated blood pressure). The prolonged-release formulation of MASDIL 300 mg allows diltiazem to be absorbed gradually, enabling once-daily administration.

2. What you need to know before taking 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 a heart rhythm or conduction disorder, 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 below 40 beats per minute).
• If you have a heart condition such as left ventricular failure with pulmonary congestion.
• If you are being treated with dantrolene (by intravenous infusion).
• If you are already taking a medicine containing ivabradine used to treat certain heart conditions.
• If you are already taking a medicine containing lomitapide used to treat high cholesterol levels (see section: "Taking Masdil 300 mg with other medicines").

Warnings and precautions

Talk to your doctor or pharmacist before starting Masdil 300 mg

• If you have heart conditions such as left ventricular failure, bradycardia (slow heart rate), or first-degree atrioventricular block (a type of arrhythmia) detected on electrocardiogram, your doctor will need to monitor you closely.
• If you are taking anticoagulants such as direct oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban) together with Masdil 300 mg.
• If you are elderly or have kidney or liver disease (renal or hepatic impairment), blood levels of diltiazem may be higher, so close monitoring of heart rate is necessary at the start of treatment.
• If you are undergoing general anesthesia, you must inform the anaesthetist that you are being treated with this medicine.
• If you experience mood changes, including depression, inform your doctor.
• If you are at risk of intestinal obstruction, as diltiazem, like other medicines in the same class, may reduce intestinal motility.
• If you have latent or overt diabetes mellitus. Strict monitoring is required 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 increases. Inform your doctor if you develop signs or symptoms of respiratory problems during treatment with this medicine.
• If you have a history of heart failure, new onset of breathing difficulty, slow heart rate, or low blood pressure. Cases of kidney injury 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

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

Certain medicines may interact with MASDIL 300 mg. In such cases, it may be necessary to adjust the dose or discontinue one of the medicines.

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

Combinations that are contraindicated:

• Dantrolene: concomitant use of diltiazem with dantrolene (by intravenous infusion) is contraindicated.
• Ivabradine (see section "Do not take Masdil 300 mg").
• Medicines containing lomitapide used to treat high cholesterol levels. Diltiazem may increase lomitapide concentrations, which could increase the likelihood 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 used to treat cardiovascular conditions, such as:

• Alpha-blockers, as they may enhance the hypotensive effect (lowering of blood pressure).

• Beta-blockers, as cardiac disorders may occur. This combination should only be used under clinical and electrocardiographic monitoring, especially at the beginning of treatment.

• An increased risk of depression has been observed when diltiazem is used with beta-blockers (see section 4 Possible side effects).

• Amiodarone, digoxin, as they increase the risk of bradycardia. Caution is especially needed in elderly patients and when high doses are used.

• Other antiarrhythmic medicines, as diltiazem has antiarrhythmic properties, increasing the risk of cardiac adverse effects. This combination should only be used under clinical and electrocardiographic monitoring.

• Nitrate derivatives, as they may enhance the hypotensive effect and cause fainting.

The combination of diltiazem with the following medicines increases the blood levels of these medicines, so your doctor may need to adjust their dose during treatment with diltiazem:

• Cyclosporine (an immunosuppressant used in transplant patients).

• Phenytoin (a medicine used to treat epilepsy). Monitoring of plasma phenytoin concentrations is recommended when used concomitantly with diltiazem.

• Carbamazepine (a medicine used to treat epilepsy).

• Theophylline (a medicine used for asthma).

• H2 antagonists (cimetidine and ranitidine), medicines used to treat stomach ulcers, which may increase blood levels of diltiazem; therefore, treatment with these may need to be discontinued or the daily dose of diltiazem adjusted.

• Rifampicin (an antibiotic used to treat tuberculosis and some infections), which may reduce blood levels of diltiazem; your doctor will need to monitor you closely.

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

• Lithium (a medicine used to treat mental health conditions), as it may increase lithium toxicity. Your doctor will closely monitor your blood lithium levels.

• Colchicine. Masdil 300 mg may increase colchicine levels (a medicine used to treat gout) when administered concomitantly.

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

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

General information to consider:

• Due to possible additive effects, caution and medical evaluation are required when diltiazem is administered concomitantly with other agents known to affect cardiac conduction and/or contractility.

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

• Medicines metabolized by the CYP3A4 enzyme, as this may result in decreased blood levels of diltiazem or increased blood levels of any concomitantly administered medicines.

• Patients who consume grapefruit juice should be monitored, as it 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 blood levels of these medicines, prolonging their duration in the body. Your doctor will exercise special caution when prescribing benzodiazepines (especially short-acting ones) if you are taking diltiazem.

• Corticosteroids (methylprednisolone), used as anti-inflammatory agents and for severe allergies due to their immunosuppressive effects, as diltiazem reduces the metabolism of methylprednisolone; your doctor will monitor you closely and may need to adjust the dose of methylprednisolone.

• Statins (medicines used to lower cholesterol), as diltiazem greatly increases blood levels of some statins, potentially causing statin-related toxicity.

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

Children and adolescents

MASDIL 300 mg is not suitable for children.

Taking MASDIL 300 mg with food, drinks and alcohol

The pharmacological effect of MASDIL 300 mg is not affected by food or drink. It can be taken before or during main meals, at any time of day, but it is recommended to take it at the same time each day.

Grapefruit juice should be avoided (see section "Taking Masdil 300 mg with other medicines").

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

This medicine should not be given to pregnant women or women of childbearing potential who are not using an effective method of contraception.

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

Driving and using machines

Based on the adverse effects reported with Masdil 300 mg, such as dizziness (common) and malaise (common), your ability to drive or operate machinery may be impaired, although no specific studies have been conducted.

Masdil 300 mg contains sodium carmellose

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

3. How to take Masdil 300 mg

Follow exactly the instructions for use of this medicine given by your doctor. If in doubt, consult your doctor or pharmacist again.

Remember to take your medicine.

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

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

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

• Elderly patients: see section “Warnings and precautions”.

• Patients with renal or hepatic impairment: must be used with caution. See section “Warnings and precautions”.

Substitution between diltiazem-containing products is not recommended unless you receive explicit advice from your doctor.

If you take more MASDIL 300 mg than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 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 nearest hospital emergency department. Take the medicine packaging with you so that the doctor knows what you have taken. The following effects may occur: feeling dizzy or weak, blurred vision, chest pain, difficulty breathing, fainting, unusually fast or slow heartbeat, difficulty speaking, confusion, reduced kidney function, coma, and sudden death.

Excess fluid may accumulate in the lungs (pulmonary edema), causing breathing difficulties that may develop 24–48 hours after ingestion.

In the case of a significant overdose, you 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 missed doses. If you forget to take a dose, take it as soon as you remember, and then take the next dose at the usual time. However, if it is already time for your next dose or nearly so, wait and take it at that time.

If you stop taking MASDIL 300 mg

Your doctor will advise you on how long your treatment with Masdil 300 mg should last. Do not stop the treatment earlier.

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 everyone will experience them.

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

Very common: may affect more than 1 in 10 people

Common: may affect up to 1 in 10 people

Uncommon: may affect up to 1 in 100 people

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

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

Frequency not known (cannot be estimated from available data)

Blood and lymphatic system disorders:

Frequency not known: thrombocytopenia.

Metabolism and nutrition disorders:

Frequency not known: hyperglycaemia.

Psychiatric disorders:

Uncommon: nervousness, difficulty sleeping (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, heart's difficulty in pumping blood (congestive heart failure), heart rhythm disorder (sinus arrest), cardiac arrest (asystole).

Vascular disorders:

Common: hot flushes

Uncommon: drop in blood pressure upon rapid standing, 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:

Common: constipation, indigestion (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 period of treatment. These elevations are usually transient.

Frequency not known: hepatitis (inflammatory disease affecting the liver).

Skin and subcutaneous tissue disorders:

Common: redness of the skin (erythema)

Rare: skin irritation and itching (urticaria)

Frequency not known: sensitivity to light (photosensitivity), swelling of the throat, lips and airways (angioneurotic edema), erythema multiforme (a serious skin condition associated with red spots, blisters), including rare cases of Stevens-Johnson syndrome (severe blistering reactions of the skin and mucous membranes), toxic epidermal necrolysis (a severe skin disorder involving skin peeling), sweating, exfoliative dermatitis (skin redness, itching, hair loss), acute generalized exanthematous pustulosis (sudden rash accompanied by fever, with pustules or lesions on the skin surface characterized as small, inflamed, pus-filled, and blister-like), occasionally erythematous desquamation with or without fever. A condition in which the body's immune system attacks normal tissues, causing symptoms such as swollen joints, fatigue, and skin rashes (called "lupus-like syndrome").

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

Reproductive system and breast disorders:

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

General disorders and administration site conditions:

Very common: edema in the lower limbs.

Common: malaise.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if they are possible adverse reactions not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Masdil 300 mg

No special storage conditions are required.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Keep out of the sight and reach of children.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Package contents and other information

Composition of MASDIL 300 mg prolonged-release capsules

• The active substance 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 consists of: gelatin, yellow iron oxide (E-172), titanium dioxide (E-171).

Appearance of the product and package contents

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

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.

Carrer de Sant Martí, 75-97

08107 Martorelles (Barcelona)

Spain

Date of latest revision of the leaflet: February 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/