Nitrolong (Capsules) Instructions for Use

Marketing Authorization Holder

Ozon, LLC (Russia)

ATC Code

C01DA02 (Nitroglycerin)

Active Substance

Nitroglycerin

Nitroglycerin (USP United States Pharmacopeia)

Dosage Form

Nitrolong

Extended-release capsules 5.2 mg: 10, 20, 30, 40, or 50 pcs.

Dosage Form, Packaging, and Composition

Extended-release capsules size No. 2; the capsule body is white, opaque; the capsule cap is light pink, opaque; the capsule contents are yellow spherical microgranules with a creamy or grayish tint, with a faint specific odor.

Excipients: ethylcellulose 15.86 mg, cellacefate 26.52 mg, liquid paraffin 3.38 mg, barium sulfate 8.515 mg, egg powder 2.08 mg, lactose monohydrate 3.445 mg.

Capsule body composition titanium dioxide 2%, gelatin up to 100%.
Capsule cap composition titanium dioxide 3%, iron oxide red dye 0.0857%, gelatin up to 100%.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

The drug is capsules containing nitroglycerin microgranules.

Nitrates are capable of releasing nitric oxide from their molecule, which is a natural endothelial relaxing factor – a mediator of direct activation of guanylate cyclase, involved in the formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate.

An increase in cGMP concentration leads to the relaxation of smooth muscle fibers (mainly in venules and veins).

Nitroglycerin limits reflex influences on blood vessels and the heart, carried out through sympathetic nerves; reduces the resistance of peripheral and coronary vessels; reduces venous return of blood to the heart; reduces myocardial oxygen demand; redistributes blood flow in the myocardium in favor of the ischemic focus; increases exercise tolerance in patients with angina pectoris.

The effect develops within the first hour after oral administration and lasts up to 6 hours or more.

Pharmacokinetics

Unlike sublingual nitroglycerin, orally administered nitroglycerin undergoes intensive metabolism during the “first pass” through the liver.

It is rapidly metabolized with the participation of nitrate reductase, forming di- and mononitrates (only isosorbide-5-mononitrate is active), the final metabolite is glycerol.

Bioavailability is no more than 10% compared to sublingual nitroglycerin.

Due to the slow gradual release from special extended-release capsules, it gradually enters the portal system and is rapidly destroyed by glutathione reductase, and only metabolites (approximately 40%) enter the systemic circulation.

Plasma protein binding is 60%.

It is excreted by the kidneys in the form of metabolites.

The total clearance is 25-30 l/min, and T_1/2 is up to 40 min.

Indications

Prevention of angina attacks, including patients who have had myocardial infarction.

ICD codes

Dosage Regimen

The drug should be taken on an empty stomach. The capsule is swallowed whole, without chewing, with a small amount of liquid.

Nitrolong is recommended to be taken only as prescribed by a doctor.

Nitrolong doses are determined depending on the severity of the disease.

The individual dosing regimen should include a 10-12-hour “nitrate-free” period to prevent the development of tolerance to nitrates.

Patients usually take 1 or 2 capsules twice a day – in the morning and at noon.

By skipping the evening dose, a 10-12-hour “nitrate-free” period is provided.

If necessary, the drug can be used 3 times a day while observing a 10-12-hour “nitrate-free” period.

In patients with a predominance of nocturnal angina attacks, Nitrolong should be prescribed at noon and in the evening.

The maximum daily dose is 31.2 mg (no more than 6 capsules containing 5.2 mg of nitroglycerin).

Adverse Reactions

Side effects are dose-dependent and in most cases are associated with the vasodilating effect of nitroglycerin.

From the cardiovascular system “nitrate” headache, dizziness, feeling of heat, tachycardia, palpitations, swelling of the ankles and legs, orthostatic hypotension, pronounced decrease in blood pressure (especially in case of overdose), cyanosis, fainting, paradoxical bradycardia (with acute arterial hypotension and/or fainting), angina (paradoxical reaction to the drug) with pronounced sclerosis of the coronary arteries, skin hyperemia.

From the gastrointestinal tract dryness of the oral mucosa, nausea, vomiting, abdominal pain.

From the central nervous system drowsiness, increased fatigue, with overdose – anxiety, psychotic reactions, general weakness.

From the hematopoietic system: thrombocytopenia, methemoglobinemia.

Allergic reactions skin rash, itching.

From the skin allergic dermatitis, exfoliative dermatitis.

Other blurred vision, hypothermia, increased sweating, development of tolerance (including cross-tolerance to other nitrates).

Contraindications

• Hypersensitivity to nitrates or any other components of the drug;
• Chronic heart failure with severe stenosis of the aortic, mitral valves or hypertrophic obstructive cardiomyopathy;
• Acute myocardial infarction with low left ventricular filling pressure;
• Cardiac tamponade;
• Constrictive pericarditis;
• Severe arterial hypotension (systolic blood pressure less than 100 mm Hg, diastolic blood pressure less than 60 mm Hg);
• Acute circulatory disorders (shock, collapse);
• Toxic pulmonary edema;
• Traumatic brain injury;
• Cerebrovascular accident, hemorrhagic stroke;
• Increased intracranial pressure;
• Closed-angle glaucoma;
• Concomitant use of phosphodiesterase type 5 (PDE-5) inhibitors – sildenafil, tadalafil, vardenafil;
• Age under 18 years (efficacy and safety have not been established);
• Lactose intolerance, lactase deficiency and glucose-galactose malabsorption (due to the presence of lactose in the composition).

With caution severe anemia, hyperthyroidism, atherosclerosis, severe renal failure, severe hepatic failure (risk of methemoglobinemia), increased gastrointestinal motility, malabsorption syndrome.

Use in Pregnancy and Lactation

The use of Nitrolong during pregnancy is not recommended.

Nitrolong can be used during pregnancy only in cases where the benefit of treatment for the mother outweighs the possible potential risk to the fetus.

It is not known whether nitroglycerin is excreted in breast milk, therefore, during treatment with Nitrolong, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution severe hepatic failure.

Use in Renal Impairment

With caution severe renal failure.

Pediatric Use

Contraindicated under 18 years of age (efficacy and safety have not been established).

Special Precautions

Nitrolong is not used to relieve angina attacks!

For this purpose, fast-acting forms of nitroglycerin (sublingual forms) are used.

Drug withdrawal is required only in case of severe side effects.

Patients previously treated with organic nitrates (isosorbide dinitrate, isosorbide mononitrate) may require a higher dose of nitroglycerin to achieve the desired hemodynamic effect.

During the use of Nitrolong, a significant decrease in blood pressure and dizziness may occur with a sharp transition from a “lying” or “sitting” position to a “standing” position, when drinking alcohol, exercising, and in hot weather, as well as increased angina with a sharp decrease in blood pressure, ischemia, up to the development of myocardial infarction and sudden death (paradoxical “nitrate” reactions).

The patient should be warned about the possible occurrence of headache (especially at the beginning of treatment), which is due to the mechanism of action of Nitrolong.

The severity of headache during the use of Nitrolong can be reduced by reducing its dose or by simultaneous administration of menthol-containing medicines (for example, Validol).

If blurred vision or dry mouth persists or is severe, treatment with Nitrolong should be discontinued.

When treating with Nitrolong at any time of the day, it is necessary to ensure a 12-hour “nitrate-free” period.

This helps prevent the development of tolerance to nitrates.

Withdrawal of the drug after long-term treatment with large doses should be carried out gradually.

Abrupt discontinuation of therapy can cause an exacerbation of coronary artery disease.

Influence on the ability to drive vehicles and 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 headache, pronounced decrease in blood pressure (less than 90 mm Hg) with orthostatic dysregulation, reflex tachycardia; dizziness may develop; asthenia, increased drowsiness, feeling of heat, nausea, vomiting; in more severe cases (ingestion of more than 20 mg/kg of nitroglycerin), increased sweating, dryness of the oral mucosa, visual disturbances and collapse may also be noted.

With the development of methemoglobinemia as a result of hypoxia, cyanosis, metabolic acidosis, convulsions, dyspnea and tachypnea, and coma may develop.

Treatment in case of overdose, if the patient is conscious, it is necessary to induce vomiting.

In case of a pronounced decrease in blood pressure, it is necessary to lay the patient on his back, raise his legs and immediately call a doctor.

Symptomatic agents are prescribed.

In more severe cases, infusion of fluids and phenylephrine, epinephrine and other vasodilators is performed to correct blood pressure.

For methemoglobinemia, depending on the severity, the following antidotes are recommended

1. Ascorbic acid: 1 g orally or as a sodium salt intravenously.
2. Oxygen therapy, hemodialysis, exchange blood transfusion.

Drug Interactions

Concomitant use of Nitrolong and alcohol can cause an additional decrease in blood pressure and collapse.

The antihypertensive effect of Nitrolong may be enhanced when used concomitantly with slow calcium channel blockers, beta-blockers, antihypertensive drugs, procainamide, diuretics, MAO inhibitors (MAO), vasodilators, phenothiazines or tricyclic antidepressants.

When used concomitantly with sildenafil, as well as with other PDE-5 inhibitors, a sharp decrease in blood pressure may occur, therefore concomitant use with these drugs is contraindicated.

Against the background of the use of quinidine and procainamide, orthostatic collapse may occur.

Concomitant use of nitroglycerin and dihydroergotamine may increase the bioavailability of dihydroergotamine.

Concomitant use of nitroglycerin and heparin reduces the effectiveness of the latter, which may require an increase in the dose of heparin (after discontinuation of the drug, a decrease in the dose of heparin may be required).

Long-term use of isosorbide dinitrate with nitroglycerin reduces the effect of the latter.

Pharmacokinetic adsorbents, astringents and coating agents reduce the absorption of nitroglycerin in the gastrointestinal tract.

Storage Conditions

Store the drug in a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is approved for use as an over-the-counter product.

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.