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

The active ingredient isosorbide mononitrate is the main metabolite of isosorbide dinitrate, a drug widely used to prevent and treat coronary heart disease (CHD).

From the point of view of pharmacodynamics, isosorbide mononitrate - a peripheral vasodilator with a predominant effect on venous vessels. At the molecular level, it stimulates the formation of nitric oxide (endothelial relaxing factor), which activates intracellular guanylate cyclase in the vascular endothelium, resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) mediator of vasodilation. In addition to the main effect associated with increasing the capacity of the venous bed, isosorbide mononitrate also has an effect on the arteries, causing a decrease in peripheral vascular resistance. Thus, reduces pre-load and afterload on the heart (reduces the end-diastolic volume of the left ventricle and reduces the systolic tension of its walls), improving the pumping function of the heart and reduces the need for myocardium in oxygen. Has coronary dilating effect.Promotes redistribution of coronary blood flow in areas with reduced blood circulation. Increases exercise tolerance in patients with IHD, angina pectoris.

Reduces the flow of blood to the right atrium, helps reduce blood pressure in the small circle. When ingestion of isosorbide mono-nigra antianginal effect occurs after 30 minutes and lasts 2-6 hours.

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 continuous administration of high doses of the drug should be avoided.

Pharmacokinetics:Quickly and completely absorbed from the gastrointestinal tract after ingestion. Bioavailability is 100%, which is confirmed by the achievement of approximately the same concentration in the blood plasma after ingestion and after intravenous administration. The maximum concentration (C_max) in the blood plasma is reached in about 1-1.5 hours. Isosorbide mononitrate almost completely metabolized in the liver, is not subjected to the effect of "primary passage" through the liver (as opposed to isosorbide dinitrate). Isosorbide mononitrate is excreted mainly through the kidneys - both in unchanged form and in the form of glucuronides. Metabolites are pharmacologically inactive. The half-life (T_1/2) is about 5 hours, which is 8 times higher than that of isosorbide dinitrate.

Indications:

- Ischemic heart disease: prevention of angina attacks, including after a previous myocardial infarction;

Chronic heart failure (as part of combination therapy).

Contraindications:

- Hypersensitivity to isosorbide mononitrate and other organic nitrates, as well as to other components included in the preparation;

- Acute myocardial infarction with severe arterial hypotension;

- acute circulatory failure (shock, vascular collapse);

- cardiogenic shock if it is impossible to correct the final diastolic pressure of the left ventricle with the help of intra-arterial counterpulsation or through the introduction of agents that have a positive inotropic effect;

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

- Anemia (severe form);

- toxic pulmonary edema;

- simultaneous use of phosphodiesterase-5 inhibitors (including sildenafil, vardenafil, tadalafil);

- Lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome;

- Hemorrhage in the brain;

- hypertrophic obstructive cardiomyopathy;

- constrictive pericarditis;

- cardiac tamponade;

- severe hypovolemia;

- severe aortic and subaortic stenosis, severe mitral stenosis;

- Children under 18 years of age (efficacy and safety not established).

Carefully:

- Closed-angle glaucoma (risk of increased intraocular pressure);

- arterial hypotension (apply only under the supervision of a doctor);

- Inadequate and malnutrition;

- with reduced pressure of filling the left ventricle, for example, with acute myocardial infarction (risk of lowering blood pressure and tachycardia, which may increase ischemia);

aortic and / or mitral stenosis;

- the tendency to orthostatic disorders of vascular regulation;

- severe renal insufficiency;

- Hepatic insufficiency (risk of development of methaemoglobinaemia);

- hemorrhagic stroke;

- hypothyroidism;

- diseases accompanied by increased intracranial pressure (increased pressure was noted with intravenous administration of high doses of nitroglycerin);

- recently suffered craniocerebral injury.

Pregnancy and lactation:

The drug Monochinkwe® is not recommended for use during pregnancy and during breastfeeding. The use of the drug is possible only according to the prescription of the doctor, after a thorough evaluation of the benefits to the mother and the possible risk to the fetus / child, as there are currently insufficient data on the consequences of its use in pregnant and lactating mothers. There is evidence that nitrates are excreted in breast milk and can cause methaemoglobinemia in the baby. The amount of excretion of isosorbide mononigrite into breast milk was not determined, so caution should be exercised when using the drug during breastfeeding. If the nursing mother still takes the drug Monochinkwe®, it is necessary to establish observation of the child for possible side effects from the use of the drug.

Dosing and Administration:

Inside.Tablets are taken whole, not liquid and squeezed with a sufficient amount of liquid (for example, a glass of water).

Usually prescribed 20 mg isosorbide mononitrate (16 tablets of 40 mg) -40 mg isosorbide mononitrate (1 tablet of 40 mg) 2-3 times a day with an interval of 7-8 hours.

The maximum daily dose is 120 mg.

The frequency of admission and duration of treatment is set individually by the doctor. In patients with circulatory failure after the first intake of the drug, symptoms of collapse may occur. Appearance of such symptoms, as well as "nitrate" headache, it is possible to avoid if treatment begins with taking medications with less isosorbide mononitrate.

Side effects:

The frequency is classified according to the headings according to the recommendations of the World Health Organization, depending on the occurrence of the event: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1 / 100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), including individual messages, the frequency is unknown (can not be calculated from available data).

From the central nervous system

Very often: a headache of varying intensity and duration - "nitrate" headache (it usually stops for several days with continued therapy);

Often: weakness, coming attacks of dizziness (including postural), drowsiness, blurred vision, stiffness, decreased ability to rapid mental and motor reactions (especially at the beginning of treatment);

Rarely: cerebral ischemia.

From the skin and subcutaneous tissues

Infrequent: skin rash;

Rarely: "tides" of blood to the skin of the face;

Very rarely: angioedema, Stevens-Johnson syndrome;

The frequency is unknown: exfoliative dermatitis.

From the digestive system

Infrequent: nausea, vomiting, dryness of the oral mucosa, a feeling of mild burning of the tongue;

Very rarely: heartburn.

From the side of the cardiovascular system

Often: lowering blood pressure and / or developing orthostatic hypotension after the first dose or after increasing the dose, which may be accompanied by reflex tachycardia, drowsiness, weakness, etc.

Rarely: a marked decrease in blood pressure, accompanied by nausea, vomiting, increased excitability, pallor of the skin and increased sweating; it is possible to increase the symptoms of angina pectoris (paradoxical effect of nitrates); paradoxical bradycardia, collapse, syncopal conditions.

Prolonged use of the drug can cause transient hypoxemia due to a relative redistribution of blood flow to hypoventilation alveolar sites (in patients with IHD - may lead to myocardial hypoxia).

Perhaps the development of tolerance, incl. cross-over to other nitrates (to prevent the development of tolerance, continuous intake of high doses of the drug should be avoided).

Overdose:

Symptoms:

Pronounced decrease in arterial pressure with orthostatic dysregulation, reflex tachycardia and headache. There may be weakness, dizziness, hot flashes, nausea, pale skin, threadlike pulse, vomiting and diarrhea. In high doses (more than 20 mg / kg body weight), one should expect the appearance of met-hemoglobinemia, cyanosis, dyspnea and tachypnea due to the formation of nitrite ions due to the metabolism of isosorbide mononitrate.

Very high doses can lead to increased intracranial pressure with the onset of cerebral symptoms. In chronic overdose, an increase in methemoglobin is possible.

Therapy:

In addition to general recommendations,such as gastric lavage and placement of the patient in a horizontal position (legs are high), the main indicators of vital functions should be monitored and, if necessary, adjusted. Patients with severe arterial hypotension and / or shock should be injected with fluid; 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 in the form of the sodium salt intravenously 0.1-0.15 ml / kg 1% solution up to 50 ml;

2. Oxygenotherapy, hemodialysis, exchange blood transfusion.

If there is a stopping of breathing and heart, it is necessary to begin resuscitation.

Interaction:

When used with other vasodilators, antihypertensive agents, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, slow calcium channel blockers (BCCC), diuretics, antipsychotics (antipsychotics) or tricyclic antidepressants,with inhibitors of phosphodiesterase-5, including sildenafil, vardenafil, tadalafil, as well as with ethanol, the intensification of the vasodilatory action of isosorbide mononitrate is possible.

In the case of simultaneous use with antihypertensive drugs isosorbide mononitrate in high doses can enhance their antihypertensive effect.

Simultaneous use with phosphodiesterase-5 inhibitors (including sildenafil, vardenafil, tadalafil) enhances the hypotensive effect of organic nitrates (see section "Contraindications"). Isosorbide mononitrate can act as a physiological antagonist of norepinephrine, acetylcholine, histamine and other substances. Barbiturates accelerate metabolism and reduce the concentration of isosorbide mononitrate in the blood.

Isosorbide mononitrate 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-adrenomimetics, alpha-adrenoblockers (dihydroergotamine, etc.), it is possible to reduce the antianginal effect of isosorbide mononitrate (tachycardia and marked decrease in blood pressure).

With the simultaneous use of isosorbide mononitrate with m-holinoblokatorami (atropine and others) increases the likelihood of increased intraocular pressure.

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

Ethanol can enhance the hypotensive effect of isosorbide mononitrate and affect the ability to concentrate and / or speed of psychomotor reactions. Saprotherin is a cofactor of nitric oxide synthetase. Care should be taken when using drugs containing sapropterine, with all substances that cause vasodilation due to the synthesis of nitric oxide (incl. isosorbide mononitrate).

Special instructions:

The drug Monochinkwe® should not be used to stop acute attacks of angina and treat acute myocardial infarction. During the period of therapy, it is necessary to monitor blood pressure and heart rate. In the presence of arterial hypotension, the drug should be taken only under the supervision of a doctor. It should be avoided abrupt withdrawal of the drug (dose gradually reduce).With prolonged use of the drug, the development of tolerance is possible, therefore, it is recommended to cancel for 24-48 hours or for 3-5 days, after 3-6 weeks of regular use of the drug, replacing the preparation Monochinkwe with other antianginal drugs at this time.

Patients with lability of the circulation may develop symptoms of acute circulatory failure already at the first intake of the drug. During the treatment with the drug should be excluded from drinking alcohol.

Effect on the ability to drive transp. cf. and fur:The drug Monochinkwe® can influence the ability to concentrate and / or the speed of psychomotor reactions. Therefore, when taking the drug should be careful when driving vehicles and classes of potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets of 40 mg.

Packaging:

For 15 tablets in a planar cell package (PVC blister / aluminum foil). 2 blisters together with instructions for use in a cardboard bundle.

Storage conditions:Store in a dark place at a temperature of no higher than 30 ° C.Keep out of the reach of children!

Shelf life:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N014356 / 01

Date of registration:25.12.2008 / 12.02.2018

Expiration Date:Unlimited

The owner of the registration certificate:Instituto Luzofarmaco d'Italia SpAInstituto Luzofarmaco d'Italia SpA Italy

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp02.06.2018

Illustrated instructions

Instructions

Monochinkwe® (Monocinque)