Perlinganit^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Zentiva Pivot EOOD (Bulgaria)

Manufactured By

Ever Pharma Jena, GmbH (Germany)

Labeled By

AESICA Pharmaceuticals, GmbH (Germany)

ATC Code

C01DA02 (Nitroglycerin)

Active Substance

Nitroglycerin

Nitroglycerin (USP United States Pharmacopeia)

Dosage Form

Perlinganit®

Concentrate for solution for infusion 10 mg/10 ml: amp.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion clear, colorless, odorless.

Excipients : propylene glycol – 10.3 mg, dextrose (glucose) – 494.4 mg, hydrochloric acid solution 1 M – 0-0.006%, water for injections.

10 ml – ampoules (5) – blister packs (2) – cardboard boxes.

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 active substance molecules in the walls of arterioles.

The action of nitroglycerin (glyceryl trinitrate) is mainly associated with a decrease in myocardial oxygen demand due to a reduction in preload (dilation of peripheral veins and a decrease in blood flow to the right atrium) and afterload (decrease in systemic vascular resistance). It 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 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 administration: 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, 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 intravenously using infusion pumps and non-absorbing infusion sets only. Do not use PVC containers or administration sets.

Dilute the concentrate before infusion. For continuous infusion, use Dextrose 5% or Sodium Chloride 0.9%. Do not mix with other drugs in the same infusion solution.

Initiate therapy at a rate of 5 mcg/min. Titrate the dose upwards in increments of 5 mcg/min every 3 to 5 minutes based on clinical response.

For management of congestive heart failure, the usual effective dose range is 25 to 50 mcg/min. For treatment of pulmonary edema, higher doses may be required.

In cases of perioperative hypertension, titrate the infusion rate until the desired blood pressure reduction is achieved. Monitor hemodynamic parameters continuously.

The maximum recommended dose is 80-100 mcg/min. Exceeding this dose increases the risk of excessive hypotension and methemoglobinemia.

Gradually reduce the infusion rate upon discontinuation to prevent rebound hemodynamic effects. Avoid abrupt withdrawal.

Monitor blood pressure and heart rate frequently during dose titration and throughout the infusion. Adjust dose for hypotension or tachycardia.

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, with severe anemia, in elderly patients, as well as in hypovolemia and severe liver and kidney dysfunction (parenterally).

With prolonged 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, 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 the antiplatelet effect of acetylsalicylic acid may be enhanced against the background of the use of nitroglycerin (glyceryl trinitrate).

With simultaneous use with nitroglycerin, the action of acetylcholine, histamine, and 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.