контрактне виробництво
свічки контактне виробництво
виробництво торгова марка
NITROSORBIDE
Release form
Tablets
For children
Not used
For pregnant women
Contraindicated
For nursing mothers
Contraindicated
For drivers
Contraindicated
Storage temperature
to 25 °C
INSTRUCTION
storage
active substance: isosorbide dinitrate; 1 tablet contains isosorbide dinitrate diluted 10 mg (0.01 g); excipients: calcium stearate, sugar, potato starch, lactose monohydrate.
Medicinal form
. Tablets. Main physico-chemical properties: tablets are white in color, with a flat surface and beveled edges.
Pharmacotherapeutic group
Vasodilators used in cardiology. ATX code C01D A08.
Pharmacological properties
Pharmacodynamics. Isosorbide dinitrate is one of the main antianginal agents from the group of organic nitrates, a peripheral vasodilator that affects mainly venous vessels. Like all organic nitrates, isosorbide dinitrate acts as a donor of nitric oxide (NO). NO relaxes vascular smooth muscles (mainly veins and systemic arteries) by stimulating guanylate cyclase and subsequently increasing the concentration of intracellular cyclic guanylate monophosphate (cGMP). As a result, cGMP-dependent protein kinase is stimulated and the phosphorylation of various proteins in smooth muscle cells changes. This leads to dephosphorylation of myosin light chains and a decrease in contractility. The action of isosorbide dinitrate is 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 (a decrease in total peripheral vascular resistance), as well as a direct coronary dilator effect. Isosorbide dinitrate promotes the redistribution of coronary blood circulation to areas with reduced blood supply. Increases tolerance to physical exertion in patients with coronary heart disease, angina pectoris. The use of isosorbide dinitrate improves coronary perfusion without the development of "stealing syndrome". Has an antihypertensive effect. In severe forms of heart failure due to a decrease in the tone of peripheral venous vessels, the drug reduces the load on the heart, the pressure in the vessels of the small circulatory circle, shortness of breath. Pharmacokinetics. Bioavailability after oral administration is 22% ("first pass" effect through the liver). The onset of action is noted after 15–40 minutes, the maximum effect develops after 1.5–2 hours, the total duration of action is 4–6 hours or more. It is metabolized in the liver. The elimination half-life is 4 hours, it can be extended with course use of the drug. It is almost completely excreted in the urine in the form of metabolites.
Indication
• Prevention and treatment of angina attacks, including post-infarction. • Treatment of chronic congestive heart failure in combination with cardiac glycosides and diuretics
Contraindication
• Hypersensitivity to isosorbide dinitrate, other nitrates or to any component of the drug; • increased intracranial pressure (including with brain injury, hemorrhagic stroke), as venodilatation can lead to its further increase; • pronounced arterial hypotension (systolic blood pressure below 90 mm Hg), bleeding, hypovolemia (isosorbide dinitrate, reducing venous return, can provoke syncope); • acute circulatory failure (shock, vascular collapse); • cardiogenic shock (if appropriate measures do not maintain a sufficient level of end-diastolic pressure); • angina caused by hypertrophic obstructive cardiomyopathy; • cardiac tamponade, aortic stenosis, mitral stenosis, constrictive pericarditis; • acute myocardial infarction; • primary pulmonary diseases (due to the risk of hypoxemia, which may be caused by the redistribution of blood flow in hyperventilation zones), toxic pulmonary edema, pulmonary heart; • severe anemia; • closed-angle glaucoma; • severe liver and/or kidney function disorders, hyperthyroidism; • simultaneous use with phosphodiesterase inhibitors (for example, sildenafil, tadalafil, vardenafil).
Interaction with other medicinal products and other forms of interaction
Phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) - during the use of isosorbide dinitrate, the treatment of erectile dysfunction with these drugs is contraindicated, because there is a potential danger of uncontrolled hypotension, life-threatening cardiovascular complications. If necessary, phosphodiesterase should be taken no earlier than 72 hours after taking nitrates. Alcohol - severe disulfiram-alcohol reactions are possible, including severe hypotension, collapse. Hypotensive drugs (for example, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, vasodilators), phenothiazines, other nitrates/nitrites, quinidine, novocainamide, cyclic antidepressants, monoamine oxidase (MAO) inhibitors, narcotic analgesics – potentiation of the hypotensive effect of isosorbide dinitrate, the development of orthostatic collapse is possible. Disopyramide - a possible decrease in the effectiveness of isosorbide dinitrate. Dihydroergotamine - the concentration of dihydroergotamine in the blood can increase, which leads to an increase in its hypertensive effect. Norepinephrine, acetylcholine, histamine – weakening of their effects when used with nitrates, since isosorbide dinitrate can be their physiological antagonist. Sympathomimetics (including adrenaline, ephedrine, norepinephrine, naphthyzine, mezaton, isadrine) - a possible decrease in the antianginal effect of nitrates. Heparin - a possible decrease in its anticoagulant effect. Hydralazine - improves cardiac output in heart failure when used in combination with isosorbide dinitrate. Miotic agents - isosorbide dinitrate reduces their effectiveness. Atropine and other drugs that have an M-choline blocking effect (for example, etacizin, ethmosin) - a possible decrease in the vasodilator effect of isosorbide dinitrate and an increase in intraocular pressure. Donors of sulfhydryl groups (captopril, acetylcysteine, unitiol) restore reduced sensitivity to the drug. Sapropterin (tetrahydrobiopterin, ВН4) is a cofactor of nitric oxide synthetase. With caution, use preparations containing sapropterin with any drugs that have a vasodilating effect due to the metabolism of nitric oxide or contain nitric oxide donors (including nitroglycerin (NTH), isosorbide dinitrate (ISDN), isosorbide mononitrate).
Features of use
The drug should not be used to eliminate angina attacks. Long-term use of large doses should be avoided to prevent reduction or loss of effect. In the case of "nitrate" tolerance, it is recommended to cancel Nitrosorbide for 24-48 hours or after 3-6 weeks of regular intake, take a break for 3-5 days, replacing Nitrosorbide with other anti-anginal drugs during this time. Patients should be warned that the antianginal effect of isosorbide dinitrate is closely related to its dosage regimen, so the proposed dosage schedule should be carefully followed. The drug should be prescribed with caution to patients with hypothyroidism, hypothermia, in case of insufficient nutrition, as well as to elderly patients due to age-related changes in liver, kidney and heart function, concomitant diseases and taking other medications. Nitrosorbide should be discontinued by gradually reducing the dose. To prevent arterial hypotension and "nitrate" headache, treatment should be started with the minimum dose. Aspirin and/or acetaminophen can be used to reduce isosorbide dinitrate-induced headache without adversely affecting the antianginal effect of isosorbide nitrate. Treatment with the drug can cause the development of orthostatic reactions, which occur more often with the simultaneous use of alcohol or other vasodilators. During treatment with Nitrosorbide, you should refrain from drinking alcohol. Patients with glucose-6-phosphate dehydrogenase deficiency may develop acute hemolysis (favism) when using isosorbide dinitrate. Taking isosorbide dinitrate can affect the results of colorimetric determination of cholesterol. Patients who are on maintenance therapy with the drug should be informed that they should not take drugs that contain phosphodiesterase inhibitors (for example, sildenafil, tadalafil, vardenafil) due to the risk of developing uncontrolled hypotension. In patients with closed-angle glaucoma, an increase in intraocular pressure is possible, so the use of nitrosorbide is contraindicated. Since the drug contains lactose, sugar and milk sugar, it should not be used in patients with rare hereditary conditions, such as fructose intolerance, galactose intolerance, sucrose-isomaltase deficiency, lactase deficiency, glucose-galactose malabsorption syndrome. Use during pregnancy or breastfeeding. There are insufficient data on the safety of isosorbide dinitrate during pregnancy. In the first trimester of pregnancy, the use of Nitrosorbide is contraindicated. In the II-III trimesters of pregnancy, the drug should be used only taking into account the ratio expected benefit for the mother / potential risk for the fetus. If it is necessary to use the drug, breastfeeding should be stopped. The ability to influence the speed of reaction when driving vehicles or other mechanisms. Until the individual reaction to the drug is clarified, one should refrain from driving a motor vehicle or working with other mechanisms, given that
Methods of application
The dosage and duration of therapy is determined by the doctor individually. The drug is recommended to be taken on an empty stomach, however, to reduce "nitrate" headache, it is possible to take the drug with food. For adults, take 10–20 mg (1–2 tablets) 3–4 times a day 30 minutes before meals, without chewing, with a sufficient amount of liquid. In case of insufficient effectiveness of the treatment, a gradual increase in the dose to the maximum - 120 mg per day is possible. Hemodynamic monitoring is essential for determining individual dosage in patients with persistent heart failure. The interval between taking the drug should be at least 4 hours. Elderly patients: the dose can be reduced, especially in case of impaired kidney and/or liver function. Children. There is no experience of use in children.
Overdose
Symptoms: decrease in blood pressure, pallor, increased sweating, weak pulse filling, dizziness, headache, orthostatic hypotension, weakness, reflex tachycardia, hyperthermia, nausea, vomiting, diarrhea, numbness. Since nitrite ions are released during the biotransformation of isosorbide dinitrate, the possibility of developing methemoglobinemia with cyanosis, a feeling of anxiety, loss of consciousness, and cardiac arrest cannot be excluded. With excessive doses, an increase in intracranial pressure with the appearance of cerebral symptoms, including seizures, is possible. Treatment: with arterial hypotension, the patient should be placed in a horizontal position with the lower limbs raised, to ensure the supply of oxygen. If the blood pressure does not normalize, correct the volume of circulating blood, in severe cases, administration of dopamine and sympathomimetics is indicated. The use of epinephrine (adrenaline) is contraindicated. With methemoglobinemia, depending on the severity of the condition, antidotes can be used: vitamin C (1 g orally), methylene blue (up to 50 ml of a 1% solution intravenously), toluidine blue (initially 2–4 mg/kg of body weight intravenously, then depending on severity of the condition), as well as oxygen therapy, hemodialysis, transfusion therapy. If signs of respiratory or circulatory arrest appear, resuscitation measures should be applied immediately.
Side effects
From the side of the immune system: possible allergic reactions in the form of fever, skin rashes, urticaria, itching, temporary hyperemia of the face and body; exfoliative dermatitis/ Stevens-Johnson syndrome, Quincke's edema; dilation of skin vessels with redness, feeling of heat, diaphoresis, hot flushes. From the side of the gastrointestinal tract: nausea, vomiting are possible; heartburn, constipation, a slight burning sensation in the tongue, dry mouth. On the part of the nervous system: possible dizziness, headache ("nitrate headache" at the beginning of treatment, which usually gradually decreases/disappears with further use of the drug, but can be strong and persistent), hemorrhage in the pituitary gland in patients with an undiagnosed tumor of the pituitary gland. From the side of the cardiovascular system: tachycardia, arterial hypotension; rarely – brain ischemia and collapse; orthostatic hypotension with reflex tachycardia, symptomatic palpitations and symptoms of cerebral ischemia (including drowsiness, dizziness, weakness, blurred vision) - in most cases at the beginning of treatment and when increasing the dose; peripheral edema, usually in patients with left ventricular failure; exacerbations/increases in the frequency of angina attacks associated with a decrease in blood pressure, pallor of the skin; collapse associated with bradycardia, heart rhythm disturbances and syncopal state. Alveolar hypoventilation with subsequent hypoxemia and the risk of developing hypoxia/myocardial infarction in patients with coronary heart disease. From the blood and lymphatic system: hematological side effects including methemoglobinemia, a case of isosorbide dinitrate-induced hemolytic anemia in a patient with concomitant glucose-6-phosphate dehydrogenase deficiency. On the part of the organs of vision: blurred vision; closed-angle glaucoma; cases of visual hallucinations; narrowing of the field of vision. Others: cases of tolerance to isosorbitol dinitrate, as well as cross-tolerance to other nitrates, have been described. Long-term use of high doses and/or shortening the interval between doses can lead to a decrease or even loss of the effect of the drug. Cases of a significant increase in the level of renin and aldosterone in the blood plasma, associated with a decrease in the rate of glomerular filtration and clearance of osmotically free water, have been reported in patients with liver cirrhosis, especially with ascites.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not higher than 15 ºС. Keep out of the reach of children.
Packaging
20 tablets in a blister; 2 blisters in a cardboard pack.
Leave category
By prescription.
Producer
Monfarm PJSC.
Address
Ukraine, 19161, Cherkasy region, Uman district, village Avramivka, str. Zavodska, 8.