Nitro Pohl Infuse (Concentrate) Instructions for Use

ATC Code

C01DA02 (Nitroglycerin)

Active Substance

Nitroglycerin

Nitroglycerin (USP United States Pharmacopeia)

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

A peripheral vasodilator with a predominant effect on venous vessels. An anti-anginal agent. The mechanism of action is associated with the release of the active substance nitric oxide in the 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 active substance molecules in the walls of arterioles.

The action of nitroglycerin (glyceryl trinitrate) is mainly associated with a reduction in myocardial oxygen demand due to a decrease in preload (dilation of peripheral veins and reduction of blood flow to the right atrium) and afterload (reduction in systemic vascular resistance). It promotes the redistribution of coronary blood flow to ischemic subendocardial areas of the myocardium.

It increases exercise tolerance in patients with coronary artery disease, angina pectoris. In heart failure, it promotes myocardial unloading mainly by reducing preload. It reduces pressure in the pulmonary circulation.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract and undergoes a first-pass effect through the liver. With sublingual administration, 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.

Among 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 intravenous 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 pre-hospital stage.

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

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

For topical application: prevention of angina attacks.

ICD codes

Dosage Regimen

Administer the concentrate intravenously only after dilution. Do not inject undiluted concentrate directly.

Prepare the infusion solution by transferring the contents of one or more ampoules into a 500 mL glass bottle or infusion bag of either 0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP. The resulting concentration must not exceed 400 mcg/mL.

Initiate infusion at a rate of 5 mcg/min. Titrate the dosage upward in increments of 5 mcg/min every 3 to 5 minutes based on clinical and hemodynamic response.

For management of congestive heart failure, the usual effective dose ranges from 30 to 50 mcg/min. For control of hypertension or ischemia, doses up to 100 mcg/min may be required. The maximum recommended dose is 400 mcg/min.

Use non-PVC infusion sets and containers. Nitroglycerin is readily adsorbed onto polyvinyl chloride (PVC) surfaces; specialized non-absorbing tubing is required for accurate dosing.

Monitor blood pressure and heart rate continuously during infusion. Adjust the rate to avoid excessive hypotension or tachycardia.

Gradually reduce the infusion rate when discontinuing therapy to prevent rebound hemodynamic effects. Do not abruptly stop the infusion.

Adverse Reactions

From the cardiovascular system dizziness, headache, tachycardia, skin flushing, 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 BP <100 mm Hg, diastolic BP <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 disorders, a tendency to orthostatic hypotension, in 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 topical application of nitroglycerin (glyceryl trinitrate), it should be relieved by taking glyceryl trinitrate under the tongue.

Avoid alcohol consumption during treatment.

Effect on ability to drive vehicles and operate machinery

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, an increase in the hypotensive effect of glyceryl trinitrate is possible.

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 enhancement of the antiplatelet effect of acetylsalicylic acid is possible against the background of the use of nitroglycerin (glyceryl trinitrate).

With simultaneous use with nitroglycerin, the action 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 – severe 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

Rx Only

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.