Leaflet: information for the user

MASDIL 300 mg prolonged-release capsules

Diltiazem hydrochloride

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult 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 of the disease, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

6.Contents of the pack and additional information.

MASDIL 300 mg belongs to a group of medications known as calcium channel blockers with direct cardiac effects, derived from benzotiazepine.

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

Do not take MASDIL 300 mg

• If you are allergic to hydrochloride diltiazem or to any of the other components of this medication (listed in section 6).
• If you have any heart rhythm or conduction disorders, such as sinus dysfunction 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 heart disease, such as left ventricular insufficiency with pulmonary congestion.
• If you are being treated with dantrolene (in infusion).
• If you are already taking a medication that contains ivabradina used for the treatment of some heart diseases.
• If you are already taking a medication that contains lomitapida used for the treatment of high cholesterol levels (see section: “Taking Masdil 300mg with other medications”).

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 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 diltiazem concentration in the blood may be higher, so you will need to closely monitor your heart rate at the beginning of treatment.
• In the case of general anesthesia, you should inform the anesthesiologist that you are being treated with this medication.
• If you experience mood changes, including depression, inform your doctor.
• If you have a risk of developing intestinal obstruction, as diltiazem, like other medications in the same group, can decrease intestinal movement.
• If you have diabetes mellitus, latent or manifest. You will need to have a strict control in these patients due to the possible increase in blood glucose levels.
• The use of diltiazem can induce bronchospasm, including the worsening of asthma, especially in patients with pre-existing bronchial hyperreactivity. Cases have also been reported after increasing the dose. You should inform your doctor if you experience any signs or symptoms of respiratory problems during treatment with this medication.
• If you have a history of heart failure, new difficulty breathing, slow heart rate, or low blood pressure.Cases of renal injury have been reported in patients with these conditions, so your doctor may need to monitor your renal function.

Taking Masdil 300 mg with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Certain medications may interact with MASDIL 300 mg. In these cases, it may be necessary to change the dose or discontinue treatment with one of the medications.

Particularly, do not take this medication and inform your doctor if you are taking:

Combinations that are contraindicated:

• Dantrolene: the simultaneous use of diltiazem with dantrolene (in infusion) is contraindicated.
• Ivabradina (see section “Do not take Masdil 300 mg”).
• Medications that contain lomitapida used for the treatment of high cholesterol levels. Diltiazem may increase the concentration of lomitapida, which may lead to an increase in the probability and severity of side effects related to the liver.

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

Combinations that require caution:

Medications for treating cardiovascular problems, such as:

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

• A decrease in the risk of depression has been observed when diltiazem is administered with beta blockers (see section 4 Possible side effects).

• Amiodarone, digoxin, as it increases the risk of bradycardia. You should be cautious, especially in elderly patients and when using high doses.
• Other antiarrhythmic medications, as diltiazem has antiarrhythmic properties, so there is a risk of increasing cardiac adverse effects. This combination should only be used if you are clinically monitored and by electrocardiogram.
• Nitrate derivatives, as it may increase the hypotensive effect and cause dizziness.

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

• Ciclosporin (immunosuppressive medication used in transplants)

• Fenitoína (medication for treating epilepsy). It is recommended to monitor the concentrations of fenitoína in plasma when administered concomitantly with diltiazem.

• Carbamazepina (medication for treating epilepsy)

• Teofilina (medication for asthma)

• Antagonists H2 (cimetidina and ranitidina) medications for treating stomach ulcers, as they produce an increase in the amount of diltiazem in the blood, so either the treatment with these will be interrupted or the dose of diltiazem will be adjusted.

• Rifampicina (antibiotic used for treating tuberculosis and some infections) that may produce a decrease in the amount of diltiazem in the blood, so your doctor will closely monitor you.
• Contrast medium for X-rays: patients treated with diltiazem may see an increase in cardiovascular effects, such as hypotension, when administered an intravenous bolus of an ionic contrast medium for X-rays. Special caution is required in patients who receive concomitantly diltiazem and a contrast medium for X-rays.

• Litio (medication for treating mental health problems) as it may increase the toxicity of this. Your doctor will closely monitor your lithium levels in the blood.

• Masdil 300 mg may lead to an increase in the level of colchicina (medication used for treating 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 prolongation of the QT interval (changes in the ECG, such as changes in heart rate or rhythm, with symptoms of dizziness) when administered with medications that have the potential or known to prolong the QT interval.

General information to be taken into account:

• 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 aggregation medications (medications that prevent platelets from aggregating and forming a clot): consider the possibility of the additive effect on platelet aggregation of diltiazem and antiplatelet aggregation medications (such as aspirin, ticagrelor, and cilostazol).

• Medications 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 medication that is administered with this.

• Monitor patients who consume grapefruit juice, as it may increase the adverse effects of diltiazem. Avoid grapefruit juice if an interaction is suspected.

• Benzodiacepinas (midazolam, triazolam), which are medications with sedative, anxiolytic, anticonvulsant, amnestic, and muscle relaxant effects, as diltiazem increases the amounts of these medications in the blood, prolonging their time in the body. Your doctor will have special care when prescribing benzodiacepinas (especially those with short action) if you are taking diltiazem.

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

• Estatinas (medications used to lower cholesterol), as diltiazem increases the amount of some statins in the blood, which could produce problems of statin toxicity.

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

Children and adolescents

MASDIL 300 mg is not an appropriate medication 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 at the same time every day.

Avoid taking grapefruit juice (see section “Taking Masdil 300 mg with other medications”

Pregnancy, lactation, and fertility

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

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

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

Driving and operating machinery

Based on the adverse effects reported with the use of Masdil 300 mg, such as dizziness (frequent) and discomfort (frequent), your ability to drive and operate machinery may be impaired, although no study has been conducted on this.

Masdil 300mg contains carmelosa sódica

This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially “sodium-free”.

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

Remember to take your medication.

The administration route of 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 and adjusted individually for you. Generally, the recommended doses are as follows:

- Adults: the daily dose, both for angina and hypertension, will be one capsule of MASDIL 300 mg per day, that is, 300 mg of diltiazem hydrochloride per day.

- Elderly patients: see the section “Warnings and precautions”.

• Patients with renal insufficiency or liver insufficiency: use with caution. See the section “Warnings and precautions”.

Do not recommend substituting diltiazem specialties among them unless you receive explicit 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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

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

In case of 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 forgot to take MASDIL 300 mg

Do not take a double dose to compensate for the missed doses. If you forgot 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 that time.

If you interrupt treatment with MASDIL 300 mg

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

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

Like all medicines, this medicine may cause side effects, although not everyone will experience 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 1,000 patients

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

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: hyperglycemia.

Mental and behavioural disorders:

Uncommon:anxiety, difficulty falling asleep (insomnia).

Frequency not known: mood changes including depression.

Nervous system disorders:

Common: headache, dizziness.

Frequency not known: movement disorder (extrapyramidal syndrome).

Cardiac disorders:

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

Uncommon:slow heart rate (bradycardia).

Frequency not known:sinus node block, heart failure (congestive heart failure), cardiac rhythm disorder (sinus arrest), cardiac arrest (asystole).

Vascular disorders:

Common:flushing

Uncommon:postural hypotension (dizziness or fainting when standing up) associated or not with dizziness.

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

Respiratory, thoracic and mediastinal disorders:

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

Gastrointestinal disorders:

Common: constipation, indigestion, stomach pain, nausea.

Uncommon: vomiting, diarrhea.

Rare:dry mouth.

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

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 of the liver).

Skin and subcutaneous tissue disorders:

Common: skin redness (erythema)

Rare: skin irritation and itching (urticaria)

Frequency not known:photosensitivity (sensitivity to light), inflammation of the throat, lips, and respiratory tract (angioneuritic edema), erythema multiforme (severe skin disease associated with red patches and blisters), including rare cases of Stevens-Johnson syndrome (severe skin and mucous membrane vesiculation), toxic epidermal necrolysis (peeling skin disease), sweating, exfoliative dermatitis (skin redness, itching, hair loss) generalized acute pustular exanthema (sudden rash accompanied by fever, with the formation of small, inflamed, pus-filled lesions on the skin surface), occasionally erythema desquamativum with or without fever. A condition in which the body's defense system attacks normal tissue, causing symptoms such as inflamed joints, fatigue, and skin eruptions (called "lupus-like syndrome").

Drug-induced skin eruption that may appear on the skin or mouth (pharmacological lichenoid eruption).

Reproductive and breast disorders:

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

General disorders and administration site conditions:

Very common:swelling in the lower limbs.

Common:uncomfortable feeling.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly to the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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 the sight and reach of children.

Medicines 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 the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition ofMASDIL 300 mgextended-release capsules

- The active ingredient is diltiazem hydrochloride. Eachextended-release capsulecontains 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 content of the packaging

MASDIL 300 mg capsules are opaque with a white body and yellow cap, containing a mixture of granules (“pellets”). It is presented in packaging with 28 extended-release capsules.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

EstevePharmaceuticals, S.A.

Passeig de la Zona Franca, 109

08038 Barcelona

Spain

Responsible for manufacturing

TOWA Pharmaceutical Europe, S.L.

c/ de Sant Martí, 75-97

08107Martorelles (Barcelona)

Spain

Last review date of the leaflet: February 2025

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