Deponit^® 10 (Transdermal system) Instructions for Use

Marketing Authorization Holder

Schwarz Pharma, AG (Germany)

Manufactured By

LTS Lohmann Therapie-Systeme, AG (Germany)

ATC Code

C01DA02 (Nitroglycerin)

Active Substance

Nitroglycerin

Nitroglycerin (USP United States Pharmacopeia)

Dosage Form

Deponit® 10

TTS (patch) 37.4 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Transdermal therapeutic system (patch) consisting of a white translucent backing foil in the form of a square with rounded edges and a contact surface area of 18 cm²; one side is completely covered with a self-adhesive opaque and colorless matrix containing the active substance, a protective translucent layer of square shape with rounded edges, the same size as the backing foil; the inner side is siliconized; divided by an S-shaped cut into two parts.

Excipients: acrylate-vinyl acetate copolymer (Durotak 387-2516, dry substance), backing foil – polypropylene (white translucent).

1 pc. – paper sachets (10) – cardboard packs.

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

Peripheral vasodilator from the group of nitrates. Nitrates release nitric oxide from their molecule, which is a natural endothelial relaxing factor – a mediator of direct activation of guanylate cyclase.

The increase in cGMP concentration leads to relaxation of smooth muscle fibers, mainly in venules and veins. It has antianginal and antispasmodic action, relaxes the smooth muscles of vascular walls, bronchi, gastrointestinal tract, biliary tract, and ureters. Promotes redistribution of coronary blood flow to areas with reduced circulation.

The drug has a central inhibitory effect on the sympathetic vascular tone, suppressing the vascular component of pain syndrome formation.

With prolonged or frequent use of long-acting nitrates, the development of tolerance to the drug (weakening of the therapeutic effect) is often observed. Sensitivity is restored after a break. To prevent the occurrence of tolerance, it is recommended to observe a daily, preferably nocturnal, “nitrate-free interval” of 8-12 hours. For most patients, such therapy is more effective than continuous treatment.

The transdermal therapeutic system (TTS) is a multilayer system that, after attaching the patch to the skin, provides continuous release of nitroglycerin through a permeable membrane that regulates the rate of nitroglycerin release from the drug reservoir.

The active substance gradually penetrates into the blood vessels of the skin, which ensures its circulation in the circulatory system at relatively constant concentrations for the recommended application period. After 12 hours, the TTS releases 10% of the initial nitroglycerin content. Since the same amount of nitroglycerin is constantly released from the TTS per cm² of surface, the dose received by the patient depends solely on the size of the system’s contact surface. Continuous TTS therapy can be carried out in those patients in whom the clinical effect of the drug remains practically unchanged over a long period of time. The effect when using TTS occurs within 0.5-3 hours and lasts up to 8-10 hours.

Indications

• Prevention of angina attacks (as monotherapy or in combination with other antianginal drugs);
• Chronic heart failure (as additional therapy in combination with cardiac glycosides, diuretics).

ICD codes

Dosage Regimen

The dosage regimen is set individually, taking into account the severity of the disease, clinical effect, and patient tolerance of the drug.

For prevention of angina attacks, one TTS (patch) per day is used in the morning. If necessary, the dose can be increased (2 patches are applied simultaneously). It should be taken into account that the maximum daily dose of Deponit 10 is the application of 2 patches (0.8 mg/h).

For chronic heart failure, it is recommended to initiate and conduct treatment in a hospital setting until the patient is transferred to the necessary maintenance dose. The optimal dose should be determined (taking into account clinical reactions and possible side effects). At the same time, signs of overdose (decreased blood pressure and tachycardia) should be monitored.

As with the use of other drugs of the organic nitrates group, the effect of the patch containing nitroglycerin may decrease in patients receiving long-term treatment. Such patients should remove the patch before going to bed.

Patients with angina attacks at night should apply the patch at night.

Rules for using the drug

The effectiveness of Deponit 10 does not depend on the application site (skin of the shoulder, forearm, chest, abdomen, or thigh). However, areas of skin with reduced blood supply (for example, areas of the foot with signs of hyperkeratosis) should not be used for application. The skin at the attachment site should be healthy and intact. The patch adheres better to those areas of the skin that remain relatively immobile during movement. It is not recommended to attach the patch to areas of skin with significant hair growth. Do not shave or trim hair with scissors at the patch application site, as growing hair can lift the patch, which disrupts the contact of the TTS with the skin.

Before applying the patch, the selected skin area should be washed with regular soap (there is no need to use alcohol-containing products) and dried. Before application, it is not recommended to use skin care products (cosmetic products containing oils, creams, lotions), as the use of these products disrupts contact with the skin.

If the patch is applied before water procedures, it usually adheres tightly to the skin and remains effective. However, prolonged contact with water should be avoided.

Each patch is packaged in a separate sealed sachet and should remain in it until use. The sachet is easily torn along the notches on the edges. The patch is removed from the sachet and held with both hands so that the protective foil is on top. Then, half of the patch should be folded down so that the S-shaped slit in the middle opens.

One half of the protective foil can be removed. Do not touch the adhesive surface of the patch.

The patch is applied to the prepared skin area, while the second half of the protective foil is removed.

The patch is firmly pressed with the palm so that its entire surface adheres tightly to the skin.

Adverse Reactions

Most frequently (>10% of patients), headache is noted with the use of Deponit 10 (gradually decreases over time and with continuous use of the drug).

From the cardiovascular system skin hyperemia, feeling of heat; rarely (especially with overdose) – orthostatic collapse, cyanosis, methemoglobinemia. At the beginning of treatment or when increasing the dose of the drug, an increase or decrease in blood pressure (up to collapse) is possible, accompanied by dizziness, reflex tachycardia or bradyarrhythmia, feeling of weakness, pallor of the skin, increased sweating, drowsiness or psychomotor agitation, episodes of syncope. Severe hypotension can provoke an increase in angina symptoms.

During treatment with Deponit 10, temporary hypoxemia may occur due to redistribution of blood flow to hypoventilated alveolar zones, which can lead to temporary myocardial hypoxia in patients with coronary artery disease.

From the digestive system heartburn, nausea, vomiting, dry mouth, abdominal pain.

From the CNS rarely (especially with overdose) – anxiety, psychotic reactions, lethargy, disorientation.

Allergic reactions mild tingling or burning at the patch attachment site, skin rash, skin itching; rarely – allergic contact dermatitis; in isolated cases, exfoliative dermatitis may develop (including exudative erythema, widespread impetigo, and toxicoderma).

Other blurred vision, weakness, hypothermia, methemoglobinemia.

Contraindications

• Acute vascular insufficiency (shock, vascular collapse);
• Cardiogenic shock;
• Severe arterial hypotension (systolic blood pressure below 90 mm Hg, diastolic blood pressure below 60 mm Hg);
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to nitroglycerin and/or other organic nitrates.

With caution the drug should be prescribed for hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, reduced left ventricular filling pressure (for example, in acute myocardial infarction, as the risk of decreased blood pressure and tachycardia increases, which can worsen ischemia), reduced left ventricular function (left ventricular failure), heart failure with low left ventricular filling pressure, aortic and/or mitral stenosis, arterial hypotension, increased intracranial pressure (hemorrhagic stroke, recent head trauma), severe anemia, hyperthyroidism, glaucoma (risk of increased intraocular pressure), severe renal failure, hepatic failure (risk of developing methemoglobinemia).

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, Deponit^® 10 is prescribed only if the intended benefit to the mother outweighs the potential risk to the fetus and child.

It is unknown whether the active substance passes into breast milk. Therefore, if it is necessary to prescribe the drug during lactation, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

With caution the drug should be prescribed for hepatic failure (risk of developing methemoglobinemia).

Use in Renal Impairment

With caution the drug should be prescribed for severe renal failure.

Special Precautions

Deponit^® 10 is not indicated for the relief of angina attacks. During treatment with Deponit 10, fast-acting nitrates should be additionally used to relieve an occurring angina attack.

When using Deponit 10 (especially with frequent use without application-free intervals), the development of tolerance (including cross-tolerance to other drugs of the nitrate group) is possible, which may require an increase in dose.

In acute myocardial infarction or acute heart failure, Deponit^® 10 should be used only under conditions of careful clinical monitoring of the patient.

To prevent an increase in the frequency of angina attacks, abrupt withdrawal of the drug should be avoided.

Before cardioversion or defibrillation, the TTS must be removed.

To prevent undesirable decreases in blood pressure, the dose of the drug should be selected individually. During treatment, a decrease in blood pressure and dizziness may occur with a sudden transition to an upright position from a lying or sitting position; when consuming alcohol, exercising, and in hot weather. With a sharp decrease in blood pressure, paradoxical nitrate reactions may develop (increased angina, ischemia up to myocardial infarction and sudden death).

The severity of headache during therapy with Deponit 10 can be reduced by reducing its dose and/or simultaneous administration of validol.

If blurred vision or dry mouth persists or is severe during the use of the drug, treatment should be discontinued.

Influence on the ability to drive vehicles and mechanisms

Deponit^® 10 may affect the patient’s psychomotor reaction, up to the impairment of the ability to drive vehicles or other mechanisms. During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms reflex tachycardia, asthenia, feeling of heat, nausea, vomiting; with the use of the drug in high doses (more than 20 mg/kg) – collapse, cyanosis, methemoglobinemia, dyspnea, tachypnea.

Treatment the patch must be removed. The patient should be placed in a horizontal position, lowering the head end of the bed and raising the patient’s legs.

To correct blood pressure, the use of phenylephrine, epinephrine, and other vasoconstrictors is possible.

For methemoglobinemia, depending on the severity, ascorbic acid is prescribed orally at a dose of 1 g or intravenously in the form of a sodium salt; methylene blue 0.1-0.15 ml/kg of 1% solution (up to 50 ml) intravenously; oxygen therapy. Hemodialysis and exchange blood transfusion may be used.

Drug Interactions

With simultaneous use of Deponit 10 with other vasodilators, antihypertensive drugs, beta-blockers, calcium channel blockers, phosphodiesterase type 5 inhibitors (for example, sildenafil), neuroleptics, tricyclic antidepressants, ACE inhibitors, procainamide, MAO inhibitors, ethanol, an enhancement of the hypotensive effect is possible.

With simultaneous use of Deponit 10 with dihydroergotamine, an increase in the concentration of the latter in the blood and an enhancement of the antihypertensive effect are noted.

With simultaneous use of Deponit 10 and heparin, the effectiveness of the latter decreases (after discontinuation of the drug, a pronounced decrease in blood coagulability is possible, which may require a reduction in the heparin dose).

Storage Conditions

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F). The patch can be disposed of with regular household waste.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.