Active substanceIsosorbide mononitrateIsosorbide mononitrate
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  • Dosage form: & nbsppills
    Composition:

    1 tablet contains:

    active substance: isosorbide mononitrate 60%, diluted in lactose - 33,33 mg or 66,67 mg, in terms of isosorbide mononitrate - 20 mg or 40 mg;

    Excipients: lactose monohydrate 105.07 mg or 205.33 mg, microcrystalline cellulose 16.00 mg or 47.60 mg, croscarmellose sodium (impellose) 0.8 mg or 10.2 mg, talc 3.20 mg or 6 , 80 mg, magnesium stearate -1.60 mg or 3.40 mg.

    Description:Tablets are white or white with a grayish hue, round, flat-cylindrical with a bevel (for a dosage of 20 mg) or white or white tablets with a grayish hue, round, flat-cylindrical with a facet and a risk (for a dosage of 40 mg).
    Pharmacotherapeutic group:Vasodilating agent - nitrate
    ATX: & nbsp

    C.01.D.A.14   Isosorbide mononitrate

    Pharmacodynamics:

    Peripheral vasodilator with predominant effect on venous vessels. Has vasodilator and antianginal action.

    Acts at the molecular level due to the formation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), a decrease in the calcium content in smooth muscle cells.

    Reduces preload (by expanding the peripheral veins) and postnagruzku (due to a decrease in the total peripheral vascular resistance), reduces the need for myocardium in oxygen, dilates the coronary arteries and improves coronary blood flow, promotes its redistribution in ischemic areas,reduces the final diastolic volume of the left ventricle and reduces the systolic tension of its walls. Increases tolerance to physical activity of patients with coronary heart disease (CHD), reduces pressure in a small circle of blood circulation, contributes to regression of symptoms with pulmonary edema.

    Isosorbide mononitrate causes relaxation of the musculature of the bronchi, urinary tract, gall bladder muscles, biliary tract and esophagus, as well as the small and large intestine, including sphincters.

    When ingestion of isosorbide mononitrate antianginal effect manifests itself after 30 minutes and lasts 2-6 hours.

    Pharmacokinetics:

    Quickly and completely absorbed after ingestion. Bioavailability ranges from 90 to 100%. The maximum concentration in the blood plasma is reached after approximately 1-1.5 hours. The therapeutic concentration of isosorbide mononitrate in the blood is reached after 30 minutes and is 250 ng / ml, during the 4th hour - 414 ng / ml, during the 12th hour - 199 ng / ml (ie, the concentration drop is slow). Isosorbide mononitrate almost completely metabolized in the liver, is not exposed to the effect of "primary transmission" through the liver.Metabolites are pharmacologically inactive. Isosorbide mononitrate is excreted by the kidneys almost exclusively in the form of metabolites. Approximately 2% is displayed unchanged. The renal clearance is 1.8 l / min. The half-life is 4-5 hours.

    Lack of liver and kidney function does not have a significant effect on the pharmacokinetics of the drug. Efficiency varies according to individual sensitivity.

    The development of tolerance, as well as cross-tolerance with other nitrocompounds in long-term continuous treatment with high doses of isosorbide mononitrate, is described. To prevent a decrease or loss of efficacy, continuous intake of high doses of the drug should be avoided.

    Indications:Prevention of attacks of stable angina pectoris, including in the post-infarction period; chronic heart failure (combination therapy).
    Contraindications:

    - Pexcessive sensitivity to organic nitrates or other components of the drug;

    - acute circulatory disorders (shock, vascular collapse);

    - acute myocardial infarction with severe arterial hypotension;

    - cardiogenic shock if a sufficiently high end-diastolic pressure in the left ventricle is not achieved by using intra-aortic counterpulsation or by administering agents that have a positive inotropic effect;

    - toxic pulmonary edema;

    - anemia (severe form);

    - severe aortic and mitral stenosis, severe hypovolemia;

    - severe arterial hypotension (systolic blood pressure (BP) less than 90 mm Hg, diastolic blood pressure less than 60 mm Hg);

    - simultaneous administration of phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, tadalafil, as they potentiate the hypotensive effect of nitrates;

    - hypertrophic cardiomyopathy;

    - constrictive pericarditis;

    - cardiac tamponade;

    - hemorrhagic stroke;

    - hereditary intolerance to galactose, a deficiency of lactase or a syndrome of glucose-galactose malabsorption;

    - age to 18 years (efficacy and safety not established).

    Carefully:

    - Low filling pressure for acute myocardial infarction, left ventricular inadequacy. Do not lower the systolic blood pressure below 90 mm Hg. p.

    - aortic and / or mitral stenosis;

    - propensity to orthostatic reactions of vascular regulation;

    - with angle-closure glaucoma (risk of increased intraocular pressure);

    - severe renal insufficiency;

    - with hepatic insufficiency (risk of development of methemoglobinemia);

    - hypothyroidism;

    - diseases accompanied by increased intracranial pressure;

    - recently suffered craniocerebral trauma;

    - inadequate and malnutrition.

    Pregnancy and lactation:

    It is not recommended during pregnancy, in experimental conditions, the animals did not have a negative effect on the fetus (teratogenic effect). There are no reliable clinical data confirming the safety of the use of Isosorbide mononitrate in humans.

    The use of the drug during pregnancy is possible only in those cases when the expected benefit exceeds the possible risk for the fetus and the child.

    During pregnancy Isosorbide mononitrate should only be used as directed by a doctor.

    If it is necessary to use isosorbide mononitrate breastfeeding mother should stop breastfeeding.

    Dosing and Administration:

    Before using the drug, you should consult your doctor.Inside, after eating without chewing, washing with water.

    Frequency of admission and duration of treatment are set individually.

    It is advisable to start therapy with 10 mg (in this case, you can use% of other isosorbide mononitrate preparations in a 20 mg dosage form with a risk) or 20 mg twice a day. Then, gradually increase the dose to 20-40 mg per reception 2-3 times a day with an interval of 7-8 hours.

    The maximum daily dose is 120 mg.

    The duration of treatment is determined by the doctor.

    It should be avoided abrupt withdrawal of the drug (dose gradually reduce).

    If you missed taking a single dose, do not take a double dose next time, but continue to adhere to the prescribed treatment regimen.

    Side effects:

    Side effects are given with a frequency distribution and organ systems. The incidence of side effects was classified as follows: very often (≥10%), often (≥1%, <10%), infrequently (≥0.1%, <1%) and very rarely (<0.01%).

    From the nervous system: very often: a "nitrate" headache, which usually lasts for several days with the continuation of therapy; often: stiffness, drowsiness, blurred vision, decreased speed of psychomotor reactions (especially at the beginning of treatment).

    From the cardiovascular system: often: after the first dose, or after increasing the dose of drug may be a reduction in blood pressure and / or the development of orthostatic hypotension, that may be accompanied by tachycardia, lethargy, dizziness, malaise, pallor, etc. Uncommon:. in severe hypotension may increase angina (paradoxical response to nitrates) and / or severe paradoxical bradycardia, collapse, syncopal conditions; methemoglobinemia (with long-term treatment), cases of collapoid states, sometimes with bradyarrhythmia and syncope, were noted.

    From the gastrointestinal tract: infrequently: nausea, vomiting, there may be a slight burning sensation of the tongue, dryness of the oral mucosa.

    From the skin and subcutaneous tissues: infrequently: skin allergic reactions (including rash), redness of the skin of the face; very rarely: angioedema, Stevens-Johnson syndrome, exfoliative dermatitis.

    Other: sweating, increased levels of catecholamines and vanillin-succinic acid in the urine.

    Prolonged use of the drug may cause transient hypoxemia due to the relativeredistribution of blood flow to hypoventilated alveolar areas (in patients with coronary heart disease - may lead to myocardial hypoxia).

    Overdose:

    Symptoms: Decrease in blood pressure with orthostatic dysregulation, reflex tachycardia and headache. May appear weakness, dizziness, "tides" of heat, nausea, vomiting and diarrhea.

    At high doses (20 mg / kg body weight) should expect methemoglobinemia, cyanosis, dyspnea and tachypnea from the formation of nitrite ions as a result of metabolism of isosorbide mononitrate.

    Very high doses can lead to an increase in intracranial pressure with the onset of cerebral symptoms.

    In chronic overdose, an increase in the level of methemoglobin is possible, although the clinical significance of this has not yet been established.

    Treatment: In addition to general recommendations, such as gastric lavage and placement of the patient in a horizontal position with raised legs, the main indicators of vital functions should be monitored and, if necessary, adjusted. Patients with severe arterial hypotension and / or shock should be supplemented with a volume of circulating blood; in exceptional cases to improve blood circulation,it is possible to carry out infusions of norepinephrine (norepinephrine) and / or dopamine. The introduction of epinephrine (adrenaline) and related compounds is contraindicated. Depending on the degree of severity, in the cases of methemoglobinemia the following antidotes are used:

    1. Ascorbic acid: 1 g inside or in the form of sodium salt intravenously;

    2. Oxygenotherapy, hemodialysis, exchange blood transfusion.

    Interaction:

    When used with other vasodilators, antihypertensive agents, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, slow calcium channel blockers (BCCs), diuretics, antipsychotics (antipsychotics) or tricyclic antidepressants, with phosphodiesterase-5 inhibitors , including sildenafil, vardenafil, tadalafil, as well as with ethanol, it is possible to increase the antihypertensive effect of the drug Isosorbide mononitrate. Barbiturates accelerate metabolism and reduce the concentration of isosorbide mononitrate in the blood.

    Reduces the effect of vasopressors.

    When combined with amiodarone, propranolol, BCCK (verapamil, nifedipine, etc.), it is possible to increase the antianginal effect.

    Under the influence of beta-adrenostimulants, alpha-adrenoblockers (dihydroergotamine, etc.), it is possible to reduce the antianginal effect (tachycardia and excessive BP decrease).

    When combined with M-holinoblokatorami (atropine and others) increases the likelihood of increased intraocular pressure.

    Adsorbents, astringent and enveloping medicines reduce the absorption of isosorbide mononitrate from the gastrointestinal tract.

    The therapeutic effect of norepinephrine (norepinephrine) decreases with simultaneous intake with nitrocompounds.

    Sapropterin is a coenzyme of nitric oxide synthetase. It is advisable to use caution while using saprotherin with all vasodilating agents that are associated with nitric oxide, including classic nitric oxide donators (for example, nitroglycerine, isosorbide dinitrate, isosorbide mononitrate, sodium nitroprusside, molsidomine), inhibitors of phosphodiesterase-5 and minoxidil.
    Special instructions:

    Isosorbide mononitrate should not be used to stop acute attacks of angina and acute myocardial infarction!

    During the period of therapy, it is necessary to monitor blood pressure and heart rate.

    It should be avoided abrupt withdrawal of the drug (dose gradually reduce). It is possible to develop tolerance to isosorbide mononitrate or cross tolerance to other nitro compounds (a decrease in the effectiveness of the drug due to the previous use of other nitrocompounds). To prevent the development of tolerance to the action of isosorbide mononitrate, its continuous intake in high doses should be avoided.

    Even with the first administration of the drug in patients with lability of the circulation (circulatory insufficiency), symptoms of acute circulatory failure may develop (see section "Side Effects" from the side of the nervous and cardiovascular system). "Nitrate" headaches can be largely prevented if at the beginning of therapy take isosorbide mononitrate in a dose of 10 mg (in this case, you can use 1/2 other preparations of isosorbide mononitrate in a 20 mg dosage form with a risk) or 20 mg in the morning and evening. During the treatment with the drug should be excluded from the use of ethanol.

    Effect on the ability to drive transp. cf. and fur:During treatment it is not recommended to drive vehicles and engage in other potentially dangerous activities requiring a fast psychomotor reaction.
    Form release / dosage:
    Tablets of 20 mg and 40 mg.
    Packaging:

    10 tablets per contour cell pack.

    For 1, 2, 3 or 5 contour squares with instructions for use in a pack of cardboard.

    Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:5 years. Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002349
    Date of registration:21.01.2014
    Expiration Date:21.01.2019
    The owner of the registration certificate:BIOKOM, CJSC BIOKOM, CJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp10.11.2017
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