Metoclopramidum

General characteristics. Structure:

Active ingredient: 10 mg of Metoclopramidum in 1 tablet.

The drug having pro-kinetic, antiemetic, protivoikotny effect.

Pharmacological properties:

Pharmacodynamics. Is an antagonist of dopamine (D2) receptors, and also serotoninovy (5-HT3) receptors (in high doses). Stimulates a physical activity of an upper part of a GIT (including regulates a tone of the lower esophageal sphincter at rest) and normalizes its motor function. Strengthens a tone and amplitude of gastric reductions (especially antral department), weakens a sphincter of the gatekeeper and a bulb of a duodenum, raises a peristaltics and accelerates gastric emptying. Normalizes department of bile (increases pressure in a gall bladder and bilious channels), reduces a spasm of a sphincter of Oddi, eliminates dyskinesia of a gall bladder.

Antiemetic activity is caused by blockade of the central and peripheral D2 - dopamine receptors, braking of a trigger zone of the emetic center and reduction of perception of signals from esodic visceral nerves is a consequence of what. As an antiemetic it is effective at the nausea and vomiting of various etiology including caused by cancer chemotherapy (prevention), connected with an anesthesia, side effect of drugs (drugs of a foxglove, cytostatics, antituberculous remedies, antibiotics, morphine) at diseases of a liver and kidneys, at uraemia, a craniocereberal injury, at vomiting of pregnant women, at disturbance of a diet. At migraine Metoclopramidum is applied to prevention of a gastric staz and nausea, and also to stimulation of absorption of the antimigrenozny HP accepted inside. Metoclopramidum is inefficient at vomiting of vestibular genesis.

Suppresses the central and peripheral action of Apomorphinum, increases prolactin secretion, causes tranzitorny increase in level of Aldosteronum (the short-term delay of liquid is possible), increases sensitivity of fabrics to acetylcholine (action does not depend on a vagal innervation, but is eliminated with holinoblokator).

Pharmacokinetics. It is quickly and well soaked up after intake, Cmax  is reached in 1–2 h after reception of a single dose, bioavailability — 60–80%. Linkng with proteins of plasma — about 30%. Easily passes through gistogematichesky barriers, including through GEB, a placental barrier, gets into breast milk. Distribution volume — 3,5 l/kg. It Biotransformirutsya in a liver. T1/2  at normal function of kidneys makes 4–6 h, at a renal failure — do14 h. It is removed by kidneys (at intake about 85% of a dose during 72 h appears in urine in not changed look and in the form of sulphatic and glyukuronidny conjugates).

Begins to work in 1–3 min. later in/in introductions, cherez10-15min after introduction in oil, in 30–60 min. after intake; the effect proceeds 1–2 h.

Carcinogenicity, mutagenicity, influence on fertility. In a 77 weeks research at the rats receiving the peroral doses exceeding MRDCh approximately by 40 times increase in level of prolactin which remained raised at chronic introduction is recorded. Increase in frequency of new growths of mammary glands at rodents at chronic introduction is revealed prolactin - the stimulating neuroleptics and Metoclopramidum. However in clinical and epidemiological trials communication between reception of these HP and formation of tumors is not revealed.

In Ames's test of mutagen properties of Metoclopramidum it is not revealed. In experiments on mice, rats and rabbits at in/in, in oil, п / to and peroral introduction of Metoclopramidum in the doses, by 12–250 times exceeding a dose for the person, disturbances of fertility it is not revealed.

Indications to use:

Nausea, vomiting, hiccups of various genesis (it can be in certain cases effective at the vomiting caused by radiation therapy or reception of tsitostatik), functional digestive disturbances, a gastroesophageal reflux disease, an atony and hypotonia of a stomach and duodenum (including postoperative), dyskinesia of biliary tract, a meteorism, an aggravation of a peptic ulcer of a stomach and duodenum (as a part of complex therapy), preparation for diagnostic testings of a GIT.

Route of administration and doses:

Inside, in oil, in / century. Adult: inside — on 5–10 mg 3 times a day to food; in oil or in/in — 10 mg; the maximum single dose — 20 mg, maximum daily — 60 mg (for all ways of introduction).

To children 2 years — depending on age are more senior. To patients with a liver failure the initial dose is reduced twice in connection with increase in T1/2.

At a renal failure the dose is selected depending on clearance of creatinine.

Features of use:

Use at pregnancy and feeding by a breast. In experiments on mice, rats and rabbits at in/in, in oil, п / to and peroral introduction of Metoclopramidum in the doses, by 12–250 times exceeding a dose for the person, adverse action on a fruit it is not revealed.

At pregnancy use is possible only in case of need (adequate and strictly controlled researches at the person are not conducted).

Category of action on a fruit on FDA — B. Though complications at the person are not registered, during breastfeeding it is necessary to apply with care (gets into breast milk).

The patients having hypersensitivity to Procainum or procaineamide can have hypersensitivity to Metoclopramidum.

It is not necessary to appoint after GIT operations (such as pyloroplasty or anastomosis of intestines) as muscular contractions interfere with healing of seams.

Patients can appoint Metoclopramidum with a depression in the anamnesis only if the estimated advantage exceeds potential risk.

Extrapyramidal frustration can be noted when using Metoclopramidum in therapeutic doses at patients of any age (see also "Side effects"). However more often they arise at reception of high doses. The extrapyramidal symptoms expressed, mainly, as acute dystonic reactions, were shown in the first 24–48 h treatment, arose at teenagers more often and 30 years are younger than adult patients.

Parkinsonichesky symptoms were noted usually within the first 6 months after an initiation of treatment, but could be shown also later longer span. These symptoms disappeared, as a rule, within 2–3 months after the termination of reception of Metoclopramidum.

Treatment by Metoclopramidum can lead to development of late dyskinesia, often irreversible (see also "Side effects"). The risk of development of late dyskinesia and probability that it will become irreversible increases with a duration of treatment and the general cumulative dose. At development in patients of symptoms of late dyskinesia therapy by Metoclopramidum should be stopped. At some patients symptoms can disappear partially or completely within several weeks or months after cancellation of HP. Special researches concerning risk of development of late dyskinesia at therapy by Metoclopramidum were not conducted, however in one of the published researches it is reported that prevalence of this complication makes about 20% among the patients treated by Metoclopramidum at least of 12 weeks. In this regard duration of continuous treatment should not exceed 12 weeks, except exceptional cases when the therapeutic effect as believe, outweighs risk of development of this serious complication. Late dyskinesia develops at patients of advanced age, women and patients with a diabetes mellitus more often.

There are rare messages on potentially fatal symptom complex — the antipsychotic malignant syndrome (AMS) connected with treatment by Metoclopramidum (see also "Side effects"). Clinical manifestations of NZS include a hyperthermia, muscular rigidity, consciousness disturbance, and also vegetative instability (irregular pulse or unstable the ABP, tachycardia, the increased sweating, arrhythmia). At development of NZS immediate cancellation of Metoclopramidum and other HP which are not necessary for the accompanying therapy, performing intensive symptomatic care and monitoring is necessary.

Against the background of Metoclopramidum distortion of laboratory indicators — such as functional trials of a liver, levels of Aldosteronum and prolactin in blood serum is possible.

During treatment by Metoclopramidum it is not necessary to take alcoholic beverages in order to avoid risk of development of complications.

It is necessary to consider a possibility of decrease in concentration of attention and increase in time of reaction during treatment (it is better to refuse driving of the car and work with potentially dangerous equipment).

Side effects:

Frequency of side effects correlates with a dose and duration of administration of drug.

From a nervous system and sense bodys: motive concern (about 10%), drowsiness (about 10%, a thicket at reception of high doses), unusual fatigue or weakness (about 10%). Extrapyramidal frustration, including acute dystonic reactions (0,2% at doses of 30-40 mg/days), such as convulsive twitching of facial muscles, a lockjaw, an opisthotonos, a muscle hyper tone, a spastic wryneck, a spasm of extraocular muscles (including okulogirny crisis), a rhythmic protrusion of language, bulbar type of the speech; seldom — a stridor and диспноэ, perhaps caused by a laryngospasm.

Parkinsonichesky symptoms: the bradykinesia, a tremor, muscular rigidity — manifestation dopamine - the blocking action, risk of development in children and teenagers increases at exceeding of a dose of 0,5 g/kg/days. Late dyskinesia, including the involuntary movements of language, inflation of cheeks, the uncontrollable chewing movements, the uncontrollable movements of hands and legs (see also "Precautionary measures"). Insomniya, a headache, dizziness, a disorientation, a depression (symptoms were from average to heavy degree of manifestation and included suicide thoughts and a suicide), uneasiness, confusion, a sonitus; seldom — hallucinations. There are rare messages on development of an antipsychotic malignant syndrome (a hyperthermia, muscle tension, consciousness disturbance, vegetative frustration) (see also "Precautionary measures").

From cardiovascular system and blood (a hemopoiesis, a hemostasis): hypotension/hypertensia, tachycardia/bradycardia, liquid delay.

From bodies of a GIT: lock/diarrhea, dryness in a mouth; seldom — a hepatotoxic (jaundice, disturbance of functional indicators of a liver — if Metoclopramidum was applied together with other gepatotoksichny means).

Allergic reactions: small tortoiseshell.

Others: increase of an urination, an urine incontience, at long reception in high doses — a gynecomastia, a galactorrhoea, disturbance of a menstrual cycle, an asymptomatic weak hyperemia of a mucous membrane of a nose, an agranulocytosis.

It was reported about development of a methemoglobinemia in the premature and been born in time newborns which in oil entered Metoclopramidum in doses of 1-2 mg/kg/days within 3 days and more.

Interaction with other medicines:

Neuroleptics (especially fenotiazina and derivatives of phenyl propyl ketone) increase probability of development of extrapyramidal frustration.

At simultaneous use reduces efficiency of a levodopa. At reception with the HP causing oppression of TsNS — strengthening of sedation.

At joint reception with cyclosporine the reduction of time of gastric emptying caused by Metoclopramidum can increase bioavailability of cyclosporine (monitoring of concentration of cyclosporine can be necessary).

Can reduce absorption of digoxin from a stomach (correction of a dose of digoxin can be necessary).

Can accelerate absorption of a meksiletin. Accelerates absorption of paracetamol, tetracycline.

Simultaneous use with alcohol can strengthen the oppressing effect of alcohol or Metoclopramidum on TsNS, and also to accelerate removal of alcohol from a stomach, possibly increasing thus the speed and extent of its absorption in a small bowel.

Combined use with the HP containing opioids can block action of Metoclopramidum on a GIT peristaltics.

Simultaneous use with Metoclopramidum can reduce effect of Cimetidinum owing to reduction of its absorption.

Contraindications:

Hypersensitivity, bleeding from a GIT, a stomach pyloric stenosis, mechanical intestinal impassability, perforation of a wall of a stomach or intestines (including states when strengthening of a physical activity of a GIT is undesirable), glaucoma, a pheochromocytoma (hypertensive crisis in connection with emission of catecholamines from a tumor is possible), epilepsy (weight and frequency of epileptic seizures can increase), Parkinson's disease and other extrapyramidal frustration (the aggravation is possible), prolaktinzavisimy tumors, early children's age up to 2 years (the risk of emergence of a diskinetichesky syndrome is increased).

Restrictions to use. Bronchial asthma (the risk of a bronchospasm increases), arterial hypertension (at in introduction the aggravation of symptoms owing to release of catecholamines), a liver and/or renal failure, advanced age, children's age up to 14 years (for parenteral administration is possible).

Overdose:

Symptoms: hypersomnia, confusion of consciousness, extrapyramidal frustration.

Treatment: the termination of administration of drug (the symptomatology disappears during 24 h after the end of reception).

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 10 mg, 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.