Моночинкве®

General characteristics. Structure:

Active ingredient: isosorbide-5-mononitrate - 40 mg;

excipients: lactoses monohydrate, cellulose microcrystallic, starch corn, talc, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. A peripheral vazodilatator with preferential influence on venous vessels. Has vasodilating and anti-anginal effect.

Reduces preloading (due to expansion of peripheral veins) and an afterload (owing to decrease in the general peripheric vascular resistance), reduces the need of a myocardium for oxygen, expands coronary arteries and improves a coronary blood stream, promotes its redistribution to ischemic areas, reduces the final diastolic volume of a left ventricle and reduces the systolic tension of its walls. Increases tolerance to an exercise stress of patients with the coronary heart disease (CHD), reduces pressure in a small circle of blood circulation.

Isosorbide mononitrate causes a relaxation of muscles of bronchial tubes, urinary tract, muscles of a gall bladder, biliary tract and a gullet, and also small and large intestine, including sphincters.

Nitrates act on molecular level by means of formation of an oxide of nitrogen (NO) and a cyclic guanozilmonofosfat (cGMP) which is considered a relaxation mediator. At intake of isosorbide-5-mononitrate the anti-anginal effect is shown in 30 minutes and 2-6 hours proceed.

Pharmacokinetics. It is quickly and completely soaked up after intake. Bioavailability makes from 90 to 100%. The maximum concentration in a blood plasma is reached approximately in 1-1,5 hours. Therapeutic concentration of isosorbide-5-mononitrate in blood is reached in 30 minutes and makes 250 ng/ml, within the 4th hour - 414 ng/ml, within the 12th hour - 199 ng/ml (i.e. concentration falling slow). Isosorbide-5-mononitrat it is almost completely metabolized in a liver, is not exposed to effect of "the first passing" through a liver (unlike dinitrate isosorbide). Metabolites - pharmacological are inactive. Isosorbide-5-mononitrat it is removed by kidneys almost only in the form of metabolites. About 2% are removed in not changed look. The elimination half-life makes 4-5 h that is 8 times higher, than at dinitrate isosorbide.

Tolerance development, and also cross tolerance with other nitro compounds is described at prolonged continuous treatment by high doses of isosorbide-5-mononitrate. To prevent decrease or loss of efficiency, it is necessary to avoid continuous reception of high doses of drug.

Indications to use:

• prevention of attacks of stenocardia at patients with coronary heart disease, including after the postponed myocardial infarction;
• treatment of chronic heart failure (as a part of a combination therapy).

Route of administration and doses:

Inside, after food, washing down with water, not chewing.

Frequency of reception and duration of treatment are established individually.

It is reasonable to begin therapy about 1/2 tablets (20 mg) 2 times a day. Then gradually to raise a dose to therapeutic: on 1 tablet (40 mg) on reception 2-3 times a day with an interval of 7-8 hours.

The maximum daily dose makes 120 mg.

Features of use:

Моночинкве® it is not necessary to apply to stopping of bad attacks of stenocardia and an acute myocardial infarction.

During therapy control of arterial pressure and heart rate is necessary.

It is necessary to avoid sharp drug withdrawal (to reduce a dose gradually).

Development of tolerance to Monochinkve® or cross tolerance to other nitro compounds is possible (decrease in efficiency of medicine owing to the previous use of other nitro compounds). For prevention of development of tolerance to action of Monochinkve®, it is necessary to avoid its continuous reception in high doses.

At patients with lability of blood circulation symptoms of an acute circulatory unefficiency can develop already at the first administration of drug. "Nitrate" headaches can be prevented substantially if at the beginning of therapy to accept 1/2 tablets Monochinkve® in the morning and in the evening.

During treatment by drug it is necessary to exclude the ethanol use.

Side effects:

At administration of drug in therapeutic doses of any significant side effects, as a rule, does not develop.

Very often (і 10%): The "nitrate" headache can arise in an initiation of treatment, and at therapy continuation usually passes within several days.

Often (і 1% - <10%): After the first reception or after increase in a dose of drug there can be a lowering of arterial pressure and/or development of orthostatic hypotension that can be followed by tachycardia, dizziness, and also weakness.

From a nervous system: constraint, drowsiness, a sight illegibility, decline in the ability to bystry mental and motor reactions (especially in an initiation of treatment).

Seldom (і 0,1% - <1%): Nausea, vomiting can be noted, the feeling of easy burning of language, dryness in a mouth, face reddening and skin allergic reactions is possible.

The expressed lowering of arterial pressure which is followed by weighting of symptoms of stenocardia (paradoxical reaction to nitrates).
Cases of kollaptoidny states, sometimes with a bradyarrhythmia and a faint were noted.

Separate cases (<0,01%): Exfoliative dermatitis.

Interaction with other medicines:

At use with other vazodilatator, anti-hypertensive means, inhibitors the angiotensin of the turning enzyme (ATE), beta adrenoblockers, blockers of "slow" calcium channels (BMKK), diuretics, antipsychotic means (neuroleptics) or tricyclic antidepressants, with phosphodiesterase inhibitors, including sildenafily, vardenafily, tadalafily, and also with ethanol strengthening of anti-hypertensive effect of the drug Monochinkve® is possible.

Barbiturates accelerate metabolism and reduce concentration of isosorbide of mononitrate in blood.

Reduces effect of vazopressor.

At a combination with Amiodaronum, propranolol, BMKK (verapamil, nifedipine, etc.) strengthening of anti-anginal effect is possible.

Under the influence of a beta adrenostimulyatorov, alpha adrenoblockers (dihydroergotamine, etc.) decrease in anti-anginal effect (tachycardia and excessive decrease in the ABP) is possible.

At the combined use with M-holinoblokatorami (atropine, etc.) the probability of increase in intraocular pressure increases.

The adsorbents knitting and enveloping HP reduce mononitrate isosorbide absorption from digestive tract.

The therapeutic effect of Norepinephrinum (noradrenaline) decreases at a concomitant use with nitro compounds.

Influence on ability to manage vehicles and to work with mechanisms:

During treatment it is not recommended to manage vehicles and to be engaged in other potentially dangerous types of activity demanding bystry psychomotor reaction.

Contraindications:

• hypersensitivity to organic nitrates or other components of drug;
• acute disorders of blood circulation (shock, vascular collapse);
• an acute myocardial infarction with the expressed arterial hypotension;
• cardiogenic shock if rather high end diastolic pressure in a left ventricle by use of intra aortal counterpulsation or due to introduction of the means having positive inotropic effect is not provided;
• toxic fluid lungs;
• anemia (severe form);
• the expressed arterial hypotension (systolic arterial pressure less than 90 mm hg, diastolic arterial pressure less than 60 mm hg);
• a concomitant use of inhibitors of phosphodiesterase, including sildenafit, vardenafit, tadalafit as they exponentiate anti-hypertensive effect of nitrates;
• hereditary intolerance of a galactose, deficit of lactase or sprue of glucose and galactose;
• children's and teenage age up to 18 years (efficiency and safety are not established).

With care
• hypertrophic subaortic stenosis, chronic cardial compression, pericardium tamponade;
• low filling pressure at an acute myocardial infarction,
left ventricular failure. It is not necessary to allow decrease in systolic arterial pressure below 90 mm of mercury.;
• aortal and/or mitral stenosis;
• tendency to orthostatic disturbances of vascular regulation;
• at glaucoma (risk of increase in intraocular pressure);
• heavy renal failure;
• at a liver failure (risk of development of a methemoglobinemia);
• hemorrhagic stroke;
• thyrotoxicosis;
• the diseases which are followed by the increased intracranial pressure;
• recently postponed craniocereberal injury.

Use at pregnancy and a lactation
For safety reasons Monochinkve® can be applied at pregnancy and in the period of a lactation only strictly on doctor's orders, after careful assessment of advantage and possible risk as by the present moment not enough data on effects of its use for pregnant women and nursing mothers. If the nursing mother nevertheless accepts Monochinkve®, it is necessary to establish observation of the child regarding development of possible effects of drug.

Overdose:

Symptoms:

Lowering of arterial pressure with orthostatic dysregulation, reflex tachycardia and a headache. There can be a weakness, dizziness, heat "inflows", nausea, vomiting and diarrhea. In high doses (more than 20 mg/kg of body weight) it is necessary to expect emergence of a methemoglobinemia, cyanosis, диспноэ and a tachypnea because of education nitrite ions owing to mononitrate isosorbide metabolism. Very high doses can lead to increase in intracranial pressure with emergence of cerebral symptoms.

At chronic overdose increase in level of a methemoglobin is possible though clinical value of it is not finalized yet.

Therapy:

In addition to the general recommendations, such as a gastric lavage and laying of the patient in horizontal position (legs are highly raised), it is necessary to control the main indicators of vital signs and if necessary to adjust.

Patients with the expressed arterial hypotension and/or in state of shock should enter liquid; in exceptional cases for improvement of blood circulation it is possible to carry out infusions of noradrenaline (Norepinephrinum) and/or a dopamine.

Introduction of Epinephrinum (adrenaline) and related connections contraindicated.

Depending on severity, in cases of a methemoglobinemia the following antidotes are applied:
1. Vitamin C: 1 g in or in the form of sodium salt intravenously.
2. Methylene blue: to 50 ml of 1% of solution methylene blue intravenously.
3. Toluidine blue: at first 2-4 mg/kg of body weight intravenously: then, if necessary repeated introductions on 2 mg/kg of body weight with an interval between introductions are possible at one o'clock.
4. Oxygenotherapy, hemodialysis, exchange hemotransfusion.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity of 5 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 40 mg.

On 15 tablets in a blister strip packaging (the blister from aluminum PVC/foil).

On 2 blisters together with the application instruction in a cardboard pack.