Nitrokor^® (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmstandard-Lexredstva OJSC (Russia)

ATC Code

C01DA02 (Nitroglycerin)

Active Substance

Nitroglycerin

Nitroglycerin (USP Pharmacopoeia of the United States)

Dosage Form

Nitrokor®

Sublingual tablets 0.5 mg: 40 pcs.

Dosage Form, Packaging, and Composition

Sublingual tablets white or almost white, round, flat-cylindrical, with a bevel.

* nitroglycerin with lactose, containing the active substance: nitroglycerin (calculated as 100% substance) – 0.5 mg, excipient: lactose monohydrate – 4.5 mg.

Excipients : aspartame – 0.002 mg, colloidal silicon dioxide – 0.9 mg, stearic acid – 0.4 mg, croscarmellose sodium – 1 mg, potato starch – 2.6 mg, microcrystalline cellulose – 35.098 mg.

40 pcs. – cases (1) – cardboard packs.

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

Peripheral vasodilator with a predominant effect on venous vessels. Anti-anginal agent. The mechanism of action is associated with the release of the active substance nitric oxide in vascular smooth muscle. Nitric oxide causes activation of guanylate cyclase and increases the level of cGMP, which ultimately leads to smooth muscle relaxation.

Under the influence of glyceryl trinitrate, arterioles and precapillary sphincters relax to a lesser extent than large arteries and veins. This is partly due to reflex reactions, as well as less intense formation of nitric oxide from the molecules of the active substance in the walls of arterioles.

The action of nitroglycerin (glyceryl trinitrate) is mainly associated with a decrease in myocardial oxygen demand due to a decrease in preload (dilation of peripheral veins and a decrease in blood flow to the right atrium) and afterload (decrease in total peripheral vascular resistance). Promotes the redistribution of coronary blood flow to ischemic subendocardial areas of the myocardium. Increases exercise tolerance in patients with coronary artery disease, angina pectoris. In heart failure, it promotes myocardial unloading mainly by reducing preload. Reduces pressure in the pulmonary circulation.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract and undergoes the “first-pass” effect through the liver. With sublingual use, this effect is absent, and the therapeutic concentration in the blood plasma is achieved within a few minutes. It is metabolized in the liver with the participation of nitrate reductase. Of the metabolites of nitroglycerin, dinitro derivatives can cause pronounced vasodilation; it is possible that they determine the therapeutic effect of nitroglycerin (glyceryl trinitrate) when taken orally.

Plasma protein binding is 60%. T_1/2 after oral administration is 4 hours, with sublingual administration – 20 minutes, after IV administration – 1-4 minutes. It is excreted mainly by the kidneys.

Indications

For sublingual and buccal use: relief and prevention of angina attacks; as an emergency treatment for acute myocardial infarction and acute left ventricular failure at the prehospital stage.

For oral administration: relief and prevention of angina attacks, restorative treatment after myocardial infarction.

For IV administration: acute myocardial infarction, including complicated by acute left ventricular failure; unstable angina; pulmonary edema.

For cutaneous use: prevention of angina attacks.

ICD codes

Dosage Regimen

Administer sublingually, buccally, orally, cutaneously, or intravenously by drip. Titrate the dose and regimen individually based on indication and clinical presentation.

For sublingual administration to relieve an acute angina attack: place one 0.5 mg tablet under the tongue at the onset of pain. Do not swallow or crush the tablet. Dissolution occurs within seconds. A burning sensation confirms tablet activity.

If pain persists, administer a second 0.5 mg dose after 5 minutes. Do not exceed three tablets within a 15-minute period. Seek immediate medical attention if pain continues after three doses.

For prophylaxis of angina attacks prior to anticipated exertion, administer one 0.5 mg tablet sublingually or buccally. For buccal use, place the tablet between the gum and cheek. Allow it to dissolve slowly; do not chew or swallow.

For intravenous infusion in acute settings like myocardial infarction or unstable angina, initiate at 5-10 mcg/min. Titrate the infusion rate upward by 5-10 mcg/min every 3-5 minutes until the desired hemodynamic or clinical response is achieved. Monitor blood pressure and heart rate continuously.

Monitor for signs of hypotension, especially with intravenous use. The development of tolerance is possible with continuous, long-term nitrate therapy. To prevent tolerance, implement a daily nitrate-free interval of 10-12 hours.

Adverse Reactions

From the cardiovascular system dizziness, headache, tachycardia, skin hyperemia, feeling of heat, arterial hypotension; rarely (especially with overdose) – collapse, cyanosis.

From the digestive system nausea, vomiting.

From the central nervous system rarely (especially with overdose) – anxiety, psychotic reactions.

Allergic reactions rarely – skin rash, itching.

Local reactions mild itching, burning, skin redness.

Other methemoglobinemia.

Contraindications

Shock, collapse, arterial hypotension (systolic blood pressure <100 mm Hg, diastolic blood pressure <60 mm Hg), acute myocardial infarction with severe arterial hypotension, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, toxic pulmonary edema, increased intracranial pressure (including in hemorrhagic stroke, after a recent head injury), closed-angle glaucoma with high intraocular pressure, hypersensitivity to nitrates.

Use in Pregnancy and Lactation

The use of nitroglycerin (glyceryl trinitrate) during pregnancy and lactation (breastfeeding) is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

Use in Hepatic Impairment

Use with caution in severe liver dysfunction (parenterally).

Use in Renal Impairment

Use with caution in severe renal dysfunction (parenterally).

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in patients with severe cerebral atherosclerosis, cerebrovascular accidents, with a tendency to orthostatic hypotension, with severe anemia, in elderly patients, as well as in hypovolemia and severe liver and kidney dysfunction (parenterally).

With long-term use, the development of tolerance to the action of nitrates is possible. To prevent the occurrence of tolerance, it is recommended to observe a 10-12-hour break in their use during each 24-hour cycle.

If an angina attack occurs during the cutaneous use of nitroglycerin (glyceryl trinitrate), it should be relieved by taking glyceryl trinitrate under the tongue.

During treatment, avoid alcohol consumption.

Effect on the ability to drive vehicles and mechanisms

Glyceryl trinitrate may reduce the speed of psychomotor reactions, which should be taken into account when driving vehicles or engaging in other potentially hazardous activities.

Drug Interactions

With simultaneous use with vasodilators, ACE inhibitors, calcium channel blockers, beta-blockers, diuretics, tricyclic antidepressants, MAO inhibitors, ethanol, ethanol-containing drugs, it is possible to enhance the hypotensive effect of glyceryl trinitrate.

With simultaneous use with beta-blockers, calcium channel blockers, the antianginal effect is enhanced.

With simultaneous use with sympathomimetics, a decrease in the antianginal effect of glyceryl trinitrate is possible, which, in turn, can reduce the pressor effect of sympathomimetics (as a result, arterial hypotension is possible).

With simultaneous use of agents with anticholinergic activity (including tricyclic antidepressants, disopyramide), hyposalivation, dry mouth develops.

There is limited data that acetylsalicylic acid, used as an analgesic, increases the concentration of nitroglycerin (glyceryl trinitrate) in the blood plasma. This may be accompanied by an increase in the hypotensive effect and headaches.

In a number of studies, a decrease in the vasodilating effect of nitroglycerin (glyceryl trinitrate) was observed against the background of long-term therapy with acetylsalicylic acid.

It is believed that an increase in the antiplatelet effect of acetylsalicylic acid is possible against the background of the use of nitroglycerin (glyceryl trinitrate).

With simultaneous use with nitroglycerin, the effect of acetylcholine, histamine, norepinephrine is reduced.

Against the background of intravenous administration of nitroglycerin, a decrease in the anticoagulant effect of heparin is possible.

With simultaneous use, an increase in the bioavailability of dihydroergotamine and a decrease in the antianginal effect of nitroglycerin (glyceryl trinitrate) are possible.

With simultaneous use with procainamide, an increase in the hypotensive effect and the development of collapse are possible.

With simultaneous use with rizatriptan, sumatriptan, the risk of coronary artery spasm increases; with sildenafil – the risk of severe arterial hypotension and myocardial infarction; with quinidine – orthostatic collapse is possible; with ethanol – sharp weakness and dizziness.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.