Nitrosprint - instructions for use, dose, side effects, contraindications

The effects of nitroglycerin are due to its ability to release from its molecule nitric oxide, which is a natural endothelial relaxing factor. Nitric oxide increases inside the cell concentration of cyclic guanosine monophosphate, which prevents the penetration of calcium ions into the smooth muscle cells and causes their relaxation. Relaxation of the smooth muscles of the vascular wall causes vasodilation,which reduces venous return to the heart (preload) and resistance to a large range of blood circulation (postload). This reduces the burden on the heart and the need for myocardium in oxygen.

Expansion of the coronary vessels improves coronary blood flow and promotes its redistribution in the area with reduced blood circulation, which increases the delivery of oxygen to the myocardium.

Reduction of venous return leads to a decrease in the right atrial filling pressure, an improvement in the blood supply of the subendocardial layers, a decrease in pressure in the small circulation and a regression of symptoms in pulmonary edema.

Nitroglycerine relaxes the smooth muscle cells of the bronchi, urinary tract, gallbladder, bile duct, esophagus, small and large intestine.

The action begins quickly, the effect develops within 1-1.5 minutes and lasts about 30 minutes.

Pharmacokinetics:

Suction

Nitroglycerin is very rapidly and quite fully absorbed into the systemic bloodstream after sublingual application through the oral mucosa. Bioavailability is approximately 100%, since the effect of "first passage" through the liver is excluded.The maximum concentration in the blood plasma is reached after 4 minutes.

Distribution

Connection with blood plasma proteins - 60%.

Metabolism

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

Excretion

It is excreted by the kidneys in the form of metabolites. The total ground clearance is 25-30 l / min. After taking the drug under the tongue, the elimination half-life from the blood plasma is 2.5-4.4 minutes. Less than 1% of the dose is released unchanged.

Indications:

- Cessation of angina attacks;

- prevention of angina attacks before physical exertion or emotional stress.

Contraindications:

- Hypersensitivity to the active substance, other organic nitrates or excipients;

- acute vascular insufficiency (shock, collapse);

- age under 18 years (effectiveness and safety not established);

- simultaneous administration of inhibitors of phosphodiesterase-5 (including, sildenafil, vardenafil, tadalafil, udenafil), as they potentiate the antihypertensive effect of nitrates;

- constrictive pericarditis;

- cardiac tamponade;

- Arterial hypotension with systolic pressure less than 90 mm Hg. Art. (can aggravate the condition, causing a paradoxical bradycardia and attacks of angina pectoris);

- hypertrophic obstructive cardiomyopathy (there may be an increase in angina attacks);

- severe anemia;

- severe aortic / subaortic stenosis or mitral stenosis;

- severe hypovolemia;

- head trauma;

- states with increased intracranial pressure (for example, cerebral hemorrhage, there was an increase in intracranial pressure when taking high doses of nitroglycerin);

- simultaneous application with stimulants of soluble guanylate cyclase (riotsiguat).

Carefully:

Intracranial hypertension, uncontrolled hypovolemia, in patients with heart failure with normal or low pulmonary arterial pressure, a closed-angle glaucoma with high intraocular pressure, hyperthyroidism, pulmonary edema, subarachnoid hemorrhage, recent head trauma, hemorrhagic stroke, conditions accompanied by a decrease in pressure filling of the left ventricle (acute myocardial infarction, isolated mitral stenosis),idiopathic hypertrophic subaortal stenosis, cerebral circulation, severe renal and / or hepatic insufficiency (risk of methaemoglobinaemia).

When treating with high doses, it is necessary to perform an assay for methemoglobinemia in those cases where cyanosis may develop. When using the drug, arterial hypotension and tachycardia may develop and, consequently, myocardial oxygen consumption may increase, these circumstances can lead to arrhythmia and fibrillation (sometimes fatal), especially in patients with acute myocardial infarction.

For patients with non-severe aortic / subaortic or mitral stenosis, the drug can be assigned taking into account the ratio of expected benefit to the possible risk of use.

Pregnancy and lactation:

Adequate and well-controlled studies of the safety of nitroglycerin during pregnancy have not been conducted. The use of the drug during pregnancy and during breastfeeding is possible only strictly according to the doctor's prescription, in the event that the intended benefit to the mother exceeds the possible risk to the fetus / child and should be carried out under strict medical supervision.

There is information about the penetration of nitrates into breast milk, but the exact content of nitroglycerin in breast milk has not been determined. A possible risk of methaemoglobinemia in infants has also been reported. The decision to stop breastfeeding or stop / refuse treatment should be taken after assessing the benefits of breastfeeding and therapy for a mother with a potential risk to the fetus or child.

Dosing and Administration:

The spray is sprayed sublingually.

At the first application or after prolonged non-use of the drug, it is recommended, before direct application, one dose of "dump" into the air to fill the pump chamber.

The drug should be used in the "sitting" position, remove the protective cap, keep the bottle upright, open the mouth and hold for a few seconds breath, press the dosing valve, directing the jet of the drug under the tongue, close your mouth for a few seconds, do not swallow the drug.

For arresting an attack of angina - 0,4-0,8 mg (1-2 doses) under the tongue. If necessary, you can apply again with 5-minute intervals, but not more than 1.2 mg (3 doses).If the attack does not stop within 15 minutes, you should immediately consult a doctor.

Before coronary angiography: to prevent spasm of the coronary vessels it is recommended to carry out 1-2 sprays (0.4-0.8 mg).

For preventive purposes apply 0.4 mg (1 dose) for 5-10 minutes before the estimated load.

Side effects:

To assess the incidence of adverse events, the following criteria were used (according to the classification of the World Health Organization): Often (≥10% of prescriptions); often (≥1% and <10%); infrequently (≥0.1% and <1%); rarely (≥0.01% and <0.1%); rarely (<0,01 %); frequency unknown (insufficient data to estimate the frequency of development).

From the side of the cardiovascular system: rarely - orthostatic collapse, cyanosis; frequency unknown - reflex tachycardia, lowering of arterial pressure, pallor, increased sweating.

From the digestive system: frequency unknown - dry mouth, nausea, vomiting, abdominal pain, diarrhea.

From the central nervous system: rarely - anxiety; frequency unknown - blurred vision, dizziness, nitrate headache, weakness, psychotic reactions, inhibition, disorientation.

Allergic reactions: rarely - skin rash, itching, allergic dermatitis, anaphylactic shock.

Local Reactions: frequency unknown - burning under the tongue, skin hyperemia.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms: a marked decrease in blood pressure (below 90 mm Hg), orthostatic hypotension, reflex tachycardia, headache; may develop asthenia, dizziness, increased drowsiness, a feeling of heat or chills, nausea, vomiting, convulsions, fainting.

At application of high doses (more than 20 mkg / kg) - a collapse, cyanosis, methemoglobinemia, dyspnea and tachypnea.

Treatment: When symptoms of an overdose occur, give the patient a horizontal position with raised legs and urgently call a doctor.

In severe overdose, it is necessary to take general measures that are taken with intoxication and shock (injection of fluids, norepinephrine and / or dopamine).

The use of epinephrine (adrenaline) is contraindicated.

In the development of methemoglobinemia, such antidotes and measures are shown:

1. Vitamin C: in the form of tablets - 1 g inside or intravenously - 1 g as a solution of the sodium salt of ascorbic acid.

2. Oxygenotherapy, hemodialysis, blood transfusion.

Interaction:

Simultaneous application with vasodilators, angiotensin-converting enzyme inhibitors, beta-adrenoblockers, slow calcium channel blockers, procainamide, tricyclic antidepressants, monoamine oxidase inhibitors, diuretics, neuroleptics, phosphodiesterase-5 inhibitors (including sildenafil, vardenafil, tadalafil, udenafil), as well as ethanol enhances the antihypergenic effect.

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

Simultaneous use with dihydroergotamine can lead to an increase in its concentration in the blood and an increase in blood pressure (increased bioavailability of dihydroergotamine).

Simultaneous administration of nitroglycerin and heparin reduces the effectiveness of the latter, which may require an increase in dose (after the drug can be reduced dose of heparin).

With the simultaneous use of sapropterin and nitroglycerin, there is an increased risk of arterial hypotension (t.p. sapropterine, being a coenzyme of synthetase of nitric oxide, potentiates the synthesis of an additional amount of nitric oxide).

Patients who previously received organic nitrates may require an increased dose of nitroglycerin.

Nitro compounds can reduce the therapeutic effect of norepinephrine (noradrenaline).

Barbiturates accelerate metabolism and reduce the concentration of nitro compounds in the blood plasma.

When used simultaneously with amiodarone, propranolol, blockers of "slow" calcium channels, the antianginal effect may increase.

Under the influence of beta-adrenostimulyatorov, alpha-adrenoblokatorov possible decrease in the expression of antianginal effect (tachycardia and excessive reduction in blood pressure).

Salicylates increase the level of nitroglycerin in the blood.

Donators of sulfhydryl groups (captopril, acetylcysteine, unitiol) restore a reduced sensitivity to nitroglycerin.

Atropine and other drugs that have m-holinoliticheskoe action, can reduce the effect of nitroglycerin due to reduced secretion and biosvovenie drug.

Simultaneous use of NitroSprint with the stimulant of soluble guanylate cyclase with rhyociglatecan cause the development of a marked decrease in blood pressure.

Special instructions:

In acute myocardial infarction or acute heart failure should be used only under the condition of careful monitoring of the patient.

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

To the drug, as to all organic nitrates, with frequent use, addiction develops.

Against the background of taking the drug, it is possible to significantly reduce blood pressure and the appearance of dizziness with a sharp transition to a vertical position from the "lying" or "sitting" position, with alcohol, exercise and hot weather.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities, since taking the drug may lead to a reduction in the speed of motor and mental reactions (the risk of reduced focus and dizziness).

Form release / dosage:Spray sublingual dosed, 0.4 mg / dose.

Packaging:For 15 ml (300 doses) in bottles of brown glass. Vials are supplied with a mechanical dosing pump with a nebulizer. Each label is labeled with a self-adhesive label.

Each bottle together with a nebulizer, safety cap and instruction for the use of a medicinal product for medical use is placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 30 ° C, away from fire.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:Without recipe

Registration number:LP-000236

Date of registration:16.02.2011 / 25.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:Tehnokom, OOOTehnokom, OOO Russia

Manufacturer: & nbsp

NPF MIKROHIM, OOO Ukraine

Information update date: & nbsp04.12.2016

Illustrated instructions

Instructions

Nitrosprint (Nitrosprint)