Nitromax 0.5 mg tablets №200

Nitromax (NITROMAX) instructions for use

Composition

active ingredient: 1 tablet contains 0.3 mg, 0.4 mg or 0.5 mg of nitroglycerin;
auxiliary substances : lactose monohydrate, potato starch; sugar is spherical; crospovidone; magnesium stearate.

Dosage form

Tablets sublingual.

Basic physical and chemical properties:

Tablets are white or white with a yellowish tint of color, with a flat, possibly rough surface.

Pharmacological group

Vasodilators used in cardiology . Organic nitrates. ATC code C01D A02.

Pharmacological properties

Pharmacodynamics.

The active substance of Nitromax is nitroglycerin.

Nitroglycerin acts directly on the smooth muscles of predominantly venous and arterial vessels through the nitrate receptor located in the smooth muscle shell of the vessel wall. Nitroglycerin in smooth muscles is enzymatically converted to form nitric oxide (N0), which stimulates the activity of guanylate cyclase. It is responsible for the formation of cyclic guanosine-3'5'-monophosphate (cGMP), which is a mediator of relaxation. It affects the processes of central regulation of vascular tone and the activity of the heart. Promotes the release of catecholamines in the brain and heart, which leads to a central depression of sympathetic and vasomotor tonus, an indirect sympathomimetic effect on the myocardium, changes in the conformation of the troponin-tropomyosin complex. The nature and intensity of the action of nitroglycerin on the heart and peripheral vessels depend on the interaction of central and peripheral processes. The suppression of vasoconstrictor reflexes on coronary vessels is the result of central suppression of pain impulses, contributes to the relief of pain episodes with angina pectoris. The antianginal effect of nitroglycerin is due to the normalizing effect on the exchange of electrolytes and myocardial energy, namely: the key indicators of the respiratory chain - the ratio of oxidized and reduced forms of nicotinamide coenzymes, the activity of NAD-dependent dehydrogenases. Affects the activity of the heart and hemodynamics. Under the influence of nitroglycerin, retrograde blood flow increases due to the expansion and increase in the number of functioning collaterals. Indirect sympathomimetic action, as well as cumulation of cAMP in the myocardium, lead to an increase in its contractility. In addition, nitric oxide effectively suppresses both aggregation and adhesion of platelets. Reduction of peripheral resistance and decrease in venous return - effects associated with S3-relaxation of smooth muscle vessels, a decrease in pre- and postnagruzku on the heart. The expansion of veins leads to a decrease in the amount of blood flowing to the heart, a decrease in preload, and the expansion of the arteries reduces the overall peripheral resistance and decreases the afterload, which ultimately manifests itself in facilitating the work of the heart and improving the coronary circulation.

There is a redistribution of blood circulation in the myocardium in favor of a focus of ischemia, ionotropic myocardial function is enhanced. The end-diastolic pressure in the left ventricle and the size of the heart decrease, and it improves the blood supply to the subendocardial region of the myocardium that is most vulnerable to ischemia. The weakening of peripheral venous and arterial resistance and the pressure of filling the heart with blood helps reduce the energy expenditure of the left ventricle and the need for myocardium in oxygen. Pressure in the pulmonary capillaries is reduced, which leads to the appointment of nitroglycerin in myocardial infarction with pulmonary edema, as well as in heart failure. With ischemic hypokinesia of certain parts of the myocardium, its contractility is restored. Meningeal vessels dilate, the vessels of the internal organs narrow, the pressure in the pulmonary artery system decreases due to vasodilation and the systemic effect of nitroglycerin. Nitroglycerin relaxes the smooth muscles of the bronchi, bile ducts, digestive tract and urinary tract. In the experimental study, there was no teratogenic or toxic effect on the embryo.

Pharmacokinetics.

With sublingual application, the effect develops after 1-5 minutes, lasting from 8-15 to 30 minutes.

Nitroglycerin, taken sublingually, is absorbed by the mucosa and enters mainly into the systemic circulation. Absorbed 60-75% of the dose. After 2-4 minutes after taking the maximum concentration in blood plasma is reached - 2.3 μg / l, after 8 minutes - it decreases by 50% and after 20 minutes nitroglycerin is almost not detected in the blood. Rapidly metabolized in the liver. Nitro esters of polyhydric alcohols are rapidly exposed to denitration. Denitration metabolites, for example 1,2 and 3,4-dinitrate, are weaker and have a longer half-life compared to nitroglycerin. The half-life of nitroglycerin is almost 30 minutes. Cleavage of nitro groups occurs in sequence both by the formation of inorganic nitrites, and with the formation of nitrates. From the organic part of the molecule of nitroesters, alcohols, aldehydes and organic acids are formed. After 4:00 after application of the drug, nitroesters (the starting product) are almost not determined. It is actively metabolized in the liver, kidneys and blood. Nitro esters are split in two ways: by glutathione-reductase reductase, is localized mainly in the soluble fraction of hepatocytes, and with an enzyme that does not require reduced glutathione. The drug is metabolized primarily in the arterio-venous vascular bed, diffuses into smooth muscle cells, where it is converted to nitric oxide. A small part of the drug, mainly under the influence of glutathione-S-reductase, is metabolized in the liver to di-, mononitrate and glycerol. When ingested, most of the drug is metabolized in the liver (the effect of the first passage). A significant part of dinitrate and mononitrate forms conjugates with glucuronic acid. Excretion of metabolites of nitroglycerin occurs mainly by the kidneys, some metabolites are excreted through the lungs with exhaled air. The total clearance of nitroglycerin is 25-30 liters.

The half-life is 4-5 minutes. The half-life of metabolites is 4:00.

Indications

Cupping and short-term prophylaxis of angina attacks.

Contraindications

Hypersensitivity to nitroglycerin, to the auxiliary components of the drug, nitrates. Cerebral ischemia, cardiac tamponade, hypertrophic obstructive cardiomyopathy, simultaneous use with sildenafil and other phosphodiesterase inhibitors, arterial hypotension (systolic blood pressure (BP) below 100 mm Hg, diastolic blood pressure below 60 mm Hg.), Increased intracranial pressure (including with hemorrhagic stroke, after a recent head injury), glaucoma with high intraocular pressure. Vascular collapse, shock, acute myocardial infarction, accompanied by a decrease in the filling pressure of the left ventricle (isolated mitral stenosis, constructive pericarditis), bradycardia (less than 50 beats per minute).

Interaction with other drugs and other interactions

With simultaneous use with other vasodilators, antihypertensive agents, ACE inhibitors, slow calcium channel blockers, phosphodiesterase inhibitors (see Section "Contraindications"), diuretics, tricyclic antidepressants, MAO inhibitors, ethanol and ethanol-containing drugs, beta adrenoblockers, procainamide, quinidine, novocainamide, the hypotensive effect of nitroglycerin is enhanced.

Atropine and other drugs that have M-holinoliticheskie action, can reduce the effect of nitroglycerin due to a decrease in secretion and bioavailability of the drug.

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

With simultaneous application with heparin, the anticoagulant effect of the latter can be reduced (after drug cancellation, a significant reduction in blood clotting may be required, which may require a reduction in the dose of heparin).

Phenobarbital activates the metabolism of nitrates in the liver. Alfa-adrenomimetics, histamine, pituitrin, corticosteroids, central nervous system stimulants, bee venom, snakes, excessive insolation reduce the antianginal effect of nitroglycerin. Salicylates increase the level of nitroglycerin in the blood, barbiturates accelerate its metabolism. Donators of sulfhydryl groups (captopril, acetylcysteine, unitiol) restore reduced sensitivity to nitroglycerin.

Application features

Be sure to inform your doctor about the previous reaction to taking this group. When taking Nitromax, possible significant reduction in blood pressure, dizziness when moving instantly to a vertical position from a lying or sitting position, with the use of alcohol, physical exercises and in hot weather. To Nitromax, as in other organic nitrates, with frequent use, habituation may develop, which requires an increased dose.

Use with caution in aortic stenosis, toxic pulmonary edema, patients with heart failure at normal / low arterial pressure in the pulmonary artery, hyperthyroidism.

If necessary, with the development of tolerance, you should temporarily stop taking the drug (for several days) and replace it with antianginal drugs from other pharmacotherapeutic groups. When there is a headache or migraine, improvement is achieved by the use of Validol or drops of menthol sublingually. Often poorly tolerated only the first dose, then the side effects are weakened.

Severity of headache when taking the drug can be reduced by reducing its dose and / or in the case of simultaneous reception Validol.

With caution should be used in patients with severe cerebral atherosclerosis, cerebral blood flow disorder, severe anemia, elderly patients, as well as patients with hypovolemia and with severe violations of liver and kidney function, in hyperthyroidism, aortic and mitral stenosis. When developing acute heart failure, you should carefully monitor the geodynamics.

During the treatment you can not drink alcohol, you need to be careful when doing physical exercises in the supine position, as it is possible to increase orthostatic hypotensive effects.

The risk of developing methaemoglobinemia, which is manifested by cyanosis and changes in the color of the blood, increases with prolonged uncontrolled intake of nitroglycerin, taking high doses of the drug to patients with hepatic insufficiency. With the development of methemoglobinemia, nitroglycerin must be urgently discontinued and antidote - methylthioninium chloride (methylene blue) should be applied. In the case of the need for further use of nitrates, monitoring of the content of methemoglobin is mandatory.

To reduce the risk of side effects, it is necessary: be cautious when used simultaneously with drugs that have severe hypotensive and vasodilating properties; refrain from drinking alcohol, limit stay in rooms with a high ambient temperature (sauna, sauna, hot shower), avoid taking several tablets simultaneously or sequentially in a short time after the first intake.

Tablets can not be chewed, because through the mucous membrane of the oral cavity in the systemic blood flow can enter an excessive amount of active substance.

Uncontrolled use of the drug may lead to the development of tolerance, which is reflected in a decrease in the duration and severity of the effect and the need to increase the dose to achieve a therapeutic effect. After a break in treatment, sensitivity to nitrates is restored. In order to prevent the development of tolerance, it is recommended to maintain the interval between taking nitrates daily (8-12 hours).

Before using the drug for the first time, you should consult a doctor!

If you have an intolerance to some sugars, you should consult your doctor before taking this medication.

Contains 0.005 g of sucrose per dose. Use with caution in patients with diabetes mellitus.

Contains 0.0291 g, 0.029 g and 0.0289 g of lactose per dose, respectively. Use with caution in patients with diabetes mellitus

The drug contains lactose, therefore its use is contraindicated in patients with rare hereditary conditions, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy or lactation.

The use of Nitromax during pregnancy and lactation is contraindicated.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

Admission Nitromaksu can lead to a decrease in the reaction rate, so you need to be careful when driving vehicles or other mechanisms.

Dosing and Administration

When angina pectoris should be taken sublingually immediately after the onset of an attack. Usual dose - 0.5 mg, for many patients with stable angina is effective and less dose - 0.3 mg or 0.4 mg. If there is no antianginal effect, take another 1 tablet within the first 5 minutes.

If there is no therapeutic effect after taking 1-1.5 mg of the drug, you should immediately call a doctor (probability of myocardial infarction)!

Nitromax is active for 30 minutes. With frequent attacks of angina pectoris, it is advisable to appoint prolonged drugs of the nitroglycerin series. However, if the attack of angina develops with treatment with prolonged nitrates, Nyrotax should be used to stop an acute attack. Tolerance to sublingual forms of nitrates develops rarely, however, when it occurs, in some patients the dose of the drug should be gradually increased, bringing it to 1.0-1.5 mg.

Children

Experience in the use of the drug in children there, so it is not recommended to use this age category of patients.

Overdose

Symptoms: lowering blood pressure (below 90 mm Hg) With orthostatic dysregulation, headache, severe dizziness, fainting, frequent palpitations, nausea and vomiting, shortness of breath, severe weakness, drowsiness, fever, fever, arterial hypotension, increased sweating, chills.

When using high doses (more than 20 μg / kg) - collapse, cyanosis of the lips, nails or palms, methemoglobinemia, dyspnea and tachypnea.

Treatment: to transfer the patient to a horizontal position with a low headboard, in severe cases, to appoint plasma substitutes, sympathomimetics, oxygen, with methaemoglobinemia - methylene blue.

Adverse Reactions

From the side of the central nervous system: blurred vision, headache, dizziness and a sense of weakness, anxiety, psychotic reactions, inhibition, disorientation.

From the cardiovascular system: reflex tachycardia, skin flushing, fever, arterial hypotension, including orthostatic collapse, cyanosis, pallor, methemoglobinemia.

From the side of the digestive tract: nausea, vomiting, dry mouth, abdominal pain, diarrhea.

From the immune system: allergic reactions, including skin rashes, itching anaphylactic shock.

Others: excitability, impaired vision, exacerbation of glaucoma, hypothermia.

Sometimes, with a sudden drop in blood pressure, there may be an increase in angina symptoms (paradoxical nitrate reactions).

Shelf life

2 years.

Storage conditions

Store at a temperature of no higher than 30 ° C in the original packaging. Keep out of the reach of children.

Packaging

For 50 tablets in a jar with a light-protective glass, 4 banks in a pack of cardboard. Or 100 tablets in a jar of lightproof glass, in a pack of cardboard.

Category of leave

Without recipe.