Metoclopramide solution instructions for use. Instructions for use metoclopramide (metoclopramidum). Cardiovascular system, metabolism

Dosage form

Solution for injection 0.5% 2 ml

Compound

1 ml of solution contains

active substance: metoclopramide hydrochloride - 5 mg;

Excipients: sodium chloride, disodium edetate, anhydrous sodium sulfite (E221), propylene glycol, 0.1 M hydrochloric acid, water for injection.

Description

Transparent colorless liquid.

Pharmacotherapeutic group

Drugs for the treatment of functional disorders of the gastrointestinal tract. Gastrointestinal motility stimulants. Metoclopramide.

ATX code A03F A01.

Pharmacological properties

Pharmacokinetics

The onset of action on the gastrointestinal tract is observed 1-3 minutes after intravenous administration and 10-15 minutes after intramuscular administration. 13-30% of the drug binds to plasma proteins. The volume of distribution is 3.5 l / kg. Penetrates through the blood-brain and placental barriers, excreted in breast milk. Metabolized in the liver. The half-life is 4-6 hours. Part of the dose (about 20%) is excreted in its original form, and the rest (about 80%) after metabolic transformations by the liver is excreted by the kidneys in compounds with glucuronic or sulfuric acid.

Pharmacodynamics

Metoclopramide is a central dopamine antagonist that also exerts peripheral cholinergic activity.

Two main effects of the drug are noted: antiemetic and the effect of accelerating gastric emptying and passage through the small intestine.

The antiemetic effect is caused by an action on the central zone of the brain stem (chemoreceptors - the activating zone of the vomiting center), probably due to inhibition of dopaminergic neurons.

The increase in peristalsis is also partially controlled by the higher parts of the central nervous system, but a mechanism of peripheral action may also be partially involved, together with the activation of postganglionic cholinergic receptors and, possibly, inhibition of dopaminergic receptors in the stomach and small intestine. Through the hypothalamus and parasympathetic nervous system, it regulates and coordinates the motor activity of the upper gastrointestinal tract: increases the tone of the stomach and intestines, accelerates gastric emptying, reduces gastrostasis, prevents pyloric and esophageal reflux, stimulates intestinal motility. Normalizes the secretion of bile, reduces spasm of the sphincter of Oddi without changing its tone, eliminates dyskinesia of the gallbladder.

Side effects extend mainly to extrapyramidal symptoms, which are based on the mechanism of dopamine receptor-blocking action on the central nervous system.

Long-term treatment with metoclopramide can cause an increase in serum prolactin concentration due to the lack of dopaminergic inhibition of prolactin secretion. In women, cases of galactorrhea and menstrual irregularities are described, in men - gynecomastia. However, these symptoms disappeared after treatment was stopped.

Indications for use

adults

Metoclopramide 5 mg/ml injection is indicated for adults for:

Prevention of postoperative nausea and vomiting; nausea and vomiting caused by radiotherapy;

Symptomatic treatment of nausea and vomiting, including those associated with acute migraine

Prevention of nausea and vomiting caused by radiotherapy.

Children

Metoclopramide 5 mg/ml injection is indicated for children (aged 1-18 years) for:

As a second-line agent for the prevention of delayed chemotherapy-induced nausea and vomiting

As a second-line drug for the treatment of existing postoperative nausea and vomiting.

Dosage and administration

The solution is administered intravenously or intramuscularly. IV should be given as a slow bolus injection over at least 3 minutes.

All indications (adults)

A single dose of 10 mg is recommended to prevent postoperative nausea and vomiting. For the symptomatic treatment of nausea and vomiting, including those associated with acute migraine, as well as nausea and vomiting caused by radiotherapy, the recommended single dose is 10 mg up to 3 times a day.

The recommended maximum daily dose is 30 mg or 0.5 mg/kg body weight. The duration of treatment with injectable forms should be as short as possible with the most rapid transition to oral or rectal forms of treatment.

All indications (children aged 1-18 years)

Dosing schedule

For the treatment of existing postoperative nausea and vomiting, the maximum duration of treatment is 48 hours. To prevent delayed nausea and vomiting caused by chemotherapy, the maximum duration of treatment is 5 days.

Mode of application:

An interval of at least 6 hours between two doses must be observed even in case of vomiting or refusal of the dose.

Special populations

Elderly patients

In elderly patients, the possibility of dose reduction should be considered depending on renal or hepatic function and general condition.

Patients with impaired renal function

In patients with end-stage renal dysfunction (creatinine clearance 15 ml / min), the daily dose should be reduced to 75%. In patients with moderate to severe renal impairment (creatinine clearance 15-60 ml/min), the dose should be reduced by 50%.

Patients with impaired liver function

In patients with severe hepatic impairment, the dose should be reduced by 50%.

Children

Metoclopramide is contraindicated in children under the age of 1 year.

Side effects

The assessment of side effects is based on a classification taking into account the frequency of occurrence: very often (> 1/10); often (> 1/100 -<1/10); иногда (> 1/1000 - <1/100), редко (> 1/10000 - <1/1000), очень редко (<1/10000) явления.

Often:

- drowsiness

Often:

Asthenia

Extrapyramidal disorders (especially in children and young people and / or when the recommended dose is exceeded, even after a single dose of the drug), parkinsonism, akathisia

Depression

Hypotension, especially when administered intravenously

Skin rash, redness and itching of the skin, urticaria, Quincke's edema.

Due to the presence of sodium sulfite in the dosage form, there may be isolated cases of hypersensitivity reactions, especially in patients with bronchial asthma, in the form of nausea, vomiting, wheezing, acute asthma attack, impaired consciousness or shock. These reactions may be individual.

Sometimes:

Anaphylactic shock

Rarely:

Bradycardia (especially when administered intravenously)

Amenorrhea, hyperprolactinemia

Hypersensitivity

Dystonia, dyskinesia, confusion

hallucinations

Galactorrhea

Diarrhea (when used in doses exceeding the daily dose)

Dizziness, drowsiness, restlessness

Very rarely

- convulsions, especially in patients with epilepsy

Parkinsonism (tremor, muscle twitching, bradykinesia, muscle rigidity, mask-like face) after long-term treatment with metoclopramide in some elderly patients, and also in renal failure

Tardive dyskinesia, which may be irreversible, may occur during long-term therapy with metoclopramide, mainly in elderly patients (especially women), in patients with diabetes mellitus and usually develops after discontinuation of the drug. Manifested by involuntary movements of the tongue, face, mouth, jaw, sometimes involuntary movements of the trunk and / or limbs

Neuroleptic malignant syndrome, including hyperpyrexia, altered consciousness, muscle rigidity, dysfunction of the autonomic nervous system, and elevated serum creatine phosphokinase levels. This syndrome is potentially lethal, if it occurs, metoclopramide should be stopped immediately and treatment should be started urgently (dantrolene, bromocriptine)

Depression

Hypersensitivity reactions.

unknown

Methemoglobinemia

Cardiac arrest occurring shortly after injection, atrioventricular block, QT interval prolongation

Gynecomastia

Inflammation and local phlebitis at the injection site

Anaphylactic reactions (including anaphylactic shock), especially when administered intravenously

Tardive dyskinesia, which may be permanent during or after long-term treatment, especially in elderly patients, neuroleptic malignant syndrome

Shock, fainting after injections. Acute arterial hypertension in patients with pheochromocytoma.

Skin reactions such as rash, itching, angioedema and urticaria.

With the development of these phenomena, metoclopramide is canceled.

Single:

Decrease / increase in blood pressure with intravenous administration. There have been isolated cases of supraventricular extrasystoles, ventricular extrasystoles, tachycardia and bradycardia after parenteral administration of metoclopramide, which can sometimes lead to cardiac arrest.

Extrapyramidal reactions, usually dystonia (including very rarely cases of dyskinetic syndrome), especially in children and patients under the age of 30 years, the risk of which increases when the daily dose of 0.5 mg / kg of body weight is exceeded: facial muscle spasm, trismus , rhythmic protrusion of the tongue, bulbar type of speech, spasm of the extraocular muscles, including oculogyric crises, unnatural positions of the head and shoulders, opisthotonus, muscle hypertonicity

Dry mouth

Frequency unknown:

- headache, fatigue, fear, confusion, tinnitus

Nausea, dyspepsia

After longer therapy with the drug, due to the stimulation of prolactin secretion, hyperprolactinemia, gynecomastia, galactorrhea or menstrual irregularities may occur, with the development of these phenomena, the use of metoclopramide should be discontinued.

Other:

- in adolescents and patients with severely impaired renal function (renal failure), as a result of which the excretion of metoclopramide slows down, the development of side effects is especially closely monitored. In case of their occurrence, the use of the drug is immediately stopped.

Contraindications

Hypersensitivity to any component of the drug

Bleeding from the gastrointestinal tract

Stenosis of the pylorus of the stomach

Mechanical obstruction of the gastrointestinal tract

Perforation of the stomach or intestines

Confirmed or suspected pheochromocytoma due to risk of severe episodes of hypertension

Epilepsy (increased frequency and intensity of seizures)

Parkinson's disease

Concomitant use of anticholinergic drugs, levodopa and dopaminergic agonists

History of tardive dyskinesia induced by antipsychotics or metoclopramide

History of methemoglobinemia when co-administered with metoclopramide or NADH-cytochrome b5 reductase deficiency

Prolactinoma or prolactin-dependent tumor

Children under 1 year of age due to the risk of extrapyramidal reactions

I-III trimester of pregnancy and lactation

Bronchial asthma

Drug Interactions

Combination contraindicated

Levodopa or dapaminergic agonists and metoclopramide are antagonists.

Combination to avoid

Alcohol enhances the sedative effect of metoclopramide

Combination to be taken into account

Metoclopramide increases the absorption of diazepam, tetracycline, ampicillin, paracetamol, acetylsalicylic acid, levodopa, ethanol; slows down the absorption of digoxin and cimetidine.

Anticholinergics and morphine derivatives

Anticholinergics and morphine derivatives may be mutually antagonistic to metoclopramide in their effect on gastrointestinal motility.

Depressants that depress the activity of the central nervous system (morphine derivatives, tranquilizers, sedative H1 blockers of histamine receptors, sedative antidepressants, barbiturates, clonidine and the like)

Metoclopramide potentiates the effect of sedatives that affect the central nervous system.

Antipsychotics

With the simultaneous use of Metcoclopramide with neuroleptics, the risk of developing extrapyramidal disorders increases.

Serotonergic drugs

The use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of developing serotonin syndrome.

Digoxin

Metoclopramide may decrease the bioavailability of digoxin. Close monitoring of plasma digoxin concentrations is required.

Cyclosporine

Metoclopramide increases the bioavailability of cyclosporine (Cmax by 46% and effect by 22%). Close monitoring of plasma ciclosporin concentrations is required.

Mivacurium and suxamethonium

Metoclopramide injections may prolong the duration of neuromuscular blockade (by inhibiting plasma cholinesterase).

Strong inhibitorsCYP2D6

Metoclopramide exposure is increased when coadministered with strong CYP2D6 inhibitors such as fluoxetine and paroxetine.

Infusion solutions having an alkaline environment

Metoclopramide is incompatible with alkaline infusion solutions.

Bromocriptine

Metoclopramide increases the concentration of bromocriptine.

vitamins

With the simultaneous appointment of metoclopramide with thiamine (Vitamin B1), the latter quickly disintegrates.

Aspirin, paracetamol: the effect of metoclopramide on gastric motility may alter the absorption of other concomitantly taken oral medicinal products from the gastrointestinal tract, either by decreasing absorption from the stomach or increasing absorption from the small intestine (for example, the effects of paracetamol and aspirin are enhanced).

Atovaquone: metoclopramide may reduce its plasma concentrations.

special instructions

Caution should be exercised when using metoclopramide in patients with a history of atopy (including asthma and porphyrias).

Neurological disorders

Extrapyramidal disorders may occur, especially in children and young adults and/or at high doses. These reactions are usually observed at the beginning of treatment and may occur after a single application. If extrapyramidal symptoms develop, metoclopramide should be discontinued immediately. Usually these effects disappear completely after stopping treatment, but symptomatic treatment (benzodiazepine in children and / or anticholinergic antiparkinsonian drugs in adults) may be required. Between each administration of metoclopramide, even in the case of vomiting and dose rejection, at least a 6-hour interval must be observed to avoid overdose. Long-term treatment with metoclopramide can lead to tardive dyskinesia, which is potentially irreversible, especially in the elderly. Treatment should be discontinued when clinical signs of tardive dyskinesia appear.

When metoclopramide was used in combination with neuroleptics, as well as in monotherapy with metoclopramide, the development of neuroleptic malignant syndrome was reported. In the event of the development of symptoms of neuroleptic malignant syndrome, the use of metoclopramide should be immediately discontinued and appropriate treatment initiated.

Patients under 30 years of age have a greater predisposition to the occurrence of dystonic-dyskinetic disorders during treatment with metoclopramide.

With caution, prescribe the drug to elderly patients due to the more frequent occurrence of parkinsonism.

For patients with impaired renal function, the dose should be adjusted according to the degree of impairment.

Application in geriatrics

When used in elderly patients, it must be borne in mind that with prolonged use of the drug in high or medium doses, the most common side effects are extrapyramidal disorders, especially parkinsonism and tardive dyskinesia.

Metoclopramide should be administered with caution to patients with arterial hypertension, since it is possible to increase the concentration of catecholamines in the blood plasma.

Methemoglobinemia:

Cases of methemoglobinemia have been reported, which may be associated with a deficiency of NADH-cytochrome b5 reductase. In such cases, you should immediately stop taking metoclopramide and take appropriate measures (for example, taking methylene blue).

Cardiovascular disorders:

Serious adverse reactions from the cardiovascular system have been reported, including cases of acute vascular insufficiency, severe bradycardia, cardiac arrest and an increase in the duration of the QT interval, which were observed after the use of metoclopramide in injection form, especially after intravenous administration.

With due care, metoclopramide should be used, especially when administered intravenously in the elderly, patients with impaired cardiac conduction (including prolongation of the QT interval), patients with electrolyte imbalance, bradycardia, and also in patients taking drugs that potentially lengthen the QT interval.

Intravenously, the drug should be administered by slow bolus injection (at least 3 minutes) to reduce the risk of adverse reactions (eg, arterial hypotension, akathisia).

Impaired kidney and liver function:

Dose reduction is recommended in patients with impaired renal function or severe hepatic impairment.

Metoclopramide should be used with caution in patients at risk, namely in elderly people with impaired cardiac conduction, electrolyte imbalance or bradycardia, and those taking other drugs that increase the length of the QT interval. The drug should not be used for the treatment of chronic diseases such as gastroparesis, dyspepsia and gastroesophageal reflux disease or as an adjunct to surgical or radiological procedures.

Pregnancy, lactation

Data obtained on the use of metoclopramide in pregnant women indicate the absence of fetotoxicity and the ability to cause malformations in the fetus, but embryotoxic data do not indicate the complete safety of the drug, extrapyramidal effects in newborns are not excluded.

The drug is contraindicated in the Ι trimester of pregnancy. The use of the drug in the II and III trimesters is possible only if there are vital indications.

If it is necessary to use the drug for the period of treatment, it is necessary to stop breastfeeding.

Features of the influence of the drug on the ability to drive vehicles and especially dangerous mechanisms

When using the drug, you should refrain from potentially hazardous activities that require increased attention (driving vehicles, working with other mechanisms).

Overdose

Symptoms: drowsiness, confusion, irritability, anxiety and its increase, convulsions, extrapyramidal-motor disorders, dysfunction of the cardiovascular system with bradycardia and an increase or decrease in blood pressure. Isolated cases of methemoglobinemia have been reported.

Treatment: extrapyramidal disorders are eliminated by slow administration of the biperiden antidote. In the case of large doses of metoclopramide, it must be removed from the gastrointestinal tract by gastric lavage or activated charcoal and sodium sulfate should be taken. The vital functions of the body are monitored until the symptoms of poisoning disappear completely.

Release form and packaging

2 ml of the drug in glass ampoules.

A label made of paper with a self-adhesive coating is glued onto the ampoule or applied with gravure printing ink for glass products.

5 ampoules, together with a knife for opening ampoules, are placed in a blister pack (cassette).

When packing ampoules with a colored break ring or a colored break point, the placement of knives for opening ampoules is excluded.

Do not use after the expiration date.

Holiday conditions

On prescription

Manufacturer

PJSC “Pharmaceutical firm “Darnitsa”, Ukraine

02093, Kyiv, st. Borispolskaya, 13.

active substance: metoclopramide;

1 ml of solution contains metoclopramide hydrochloride 5 mg;

Excipients: sodium chloride, disodium edetate, anhydrous sodium sulfite (E 221), propylene glycol, dilute hydrochloric acid, water for injection.

Dosage form. Injection.

Basic physical and chemical properties: clear colorless liquid.

Pharmacotherapeutic group. Peristalsis stimulants (propulsants).

ATX code A03F A01.

Pharmacological properties

Pharmacodynamics.

Metoclopramide is a central dopamine antagonist that also exerts peripheral cholinergic activity.

Two main effects of the drug are noted: antiemetic and the effect of accelerating gastric emptying and passage through the small intestine.

The antiemetic effect is caused by action on the central point of the brain stem (chemoreceptors - the activating zone of the vomiting center), probably due to inhibition of dopaminergic neurons.

The increase in peristalsis is also partially controlled by higher centers, but a mechanism of peripheral action may also be partially involved, along with activation of postganglionic cholinergic receptors and, possibly, inhibition of dopaminergic receptors in the stomach and small intestine. Through the hypothalamus and parasympathetic nervous system, it regulates and coordinates the motor activity of the upper gastrointestinal tract: increases the tone of the stomach and intestines, accelerates gastric emptying, reduces gastrostasis, prevents pyloric and esophageal reflux, stimulates intestinal motility. Normalizes the secretion of bile, reduces spasm of the sphincter of Oddi without changing its tone, eliminates dyskinesia of the gallbladder.

Undesirable effects extend mainly to extrapyramidal symptoms, which are based on the mechanism of dopamine receptor-blocking action on the central nervous system.

Pharmacokinetics.

The onset of action on the gastrointestinal tract is observed 1–3 minutes after intravenous administration and 10–15 minutes after intramuscular administration. The antiemetic effect persists for 12 hours. 13-30% of the drug binds to plasma proteins. The volume of distribution is 3.5 l / kg. Penetrates through the blood-brain and placental barriers, excreted in breast milk. Metabolized in the liver. The half-life is 4-6 hours. Part of the dose (approximately 20%) is excreted in its original form, and the rest (approximately 80%) after metabolic transformations by the liver is excreted by the kidneys in compounds with glucuronic or sulfuric acid.

In patients with severe renal insufficiency, creatinine clearance is reduced to 70%, and the plasma half-life is increased (approximately 10 hours for creatinine clearance of 10-50 ml / min and 15 hours for creatinine clearance< 10 мл / минуту).

In patients with cirrhosis of the liver, accumulation of metoclopramide was observed, which was accompanied by a decrease in plasma clearance by 50%.

clinical characteristics.

Indications

For adults: prevention of postoperative nausea and vomiting; nausea and vomiting caused by radiotherapy; symptomatic treatment of nausea and vomiting, including those associated with acute migraine.

For kids: as a second-line drug for the prevention of delayed chemotherapy-induced nausea and vomiting; treatment of postoperative nausea and vomiting.

Contraindications

Hypersensitivity to metoclopramide or to any other component of the drug;
gastrointestinal bleeding;
mechanical intestinal obstruction;
gastrointestinal perforation;
confirmed or suspected pheochromocytoma (due to the risk of severe attacks of arterial hypertension);
tardive dyskinesia, due to neuroleptics or metoclopramide, in history;
epilepsy (increased frequency and intensity of seizures);
Parkinson's disease;
simultaneous use with levodopa or dopaminergic agonists;
established methemoglobinemia with the use of metoclopramide or a history of NADH-cytochrome b5 reductase deficiency;
prolactin-dependent tumors;
increased convulsive readiness (extrapyramidal movement disorders);
the patient's age is up to 1 year (due to the risk of developing extrapyramidal disorders).

Interaction with other drugs and other types of interactions.

Contraindicated combinations.

Levodopa or dopaminergic agonists and metoclopramide are characterized by mutual antagonism.

Combinations to avoid.

Alcohol enhances the sedative effect of metoclopramide.

Combinations to watch out for.

When used concomitantly with oral medicinal products such as paracetamol, metoclopramide may interfere with their absorption by affecting gastric motility.

Anticholinergics and morphine derivatives: anticholinergics and morphine derivatives are characterized by mutual antagonism with metoclopramide regarding the effect on the motor activity of the digestive tract.

Central nervous system inhibitors (morphine derivatives, neuroleptics, sedative antihistamine-H1 receptor blockers, sedative antidepressants, barbiturates, clonidine and related drugs): potentiate the action of metoclopramide.

Antipsychotics: when using metoclopramide in combination with other antipsychotics, a cumulative effect and the appearance of extrapyramidal disorders may occur.

Serotonergic drugs: the use of metoclopramide in combination with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), may increase the risk of developing serotonin syndrome.

Digoxin: metoclopramide may decrease the bioavailability of digoxin. Plasma concentrations of digoxin should be carefully monitored.

Cyclosporine: metoclopramide increases the bioavailability of cyclosporine (C max by 46% and effect by 22%). It is necessary to carefully monitor the concentration of cyclosporine in plasma. The clinical implications of this phenomenon have not been definitively determined.

Mivacurium and suxamethonium: injection of metoclopramide may increase the duration of the neuromuscular block (due to inhibition of plasma cholinesterase).

Potent inhibitors of CYP2D6: Exposure levels of metoclopramide are increased when used concomitantly with strong inhibitors of CYP2D6, such as fluoxetine and paroxetine. Although the clinical significance of this is not exactly known, patients should be monitored for adverse reactions. Metoclopramide may prolong action succinylcholine.

Application features

The drug should not be used for the treatment of chronic diseases such as gastroparesis, dyspepsia and gastroesophageal reflux disease, or as an adjunct to surgical or radiological procedures.

Patients under 30 years of age are more likely to develop dystonic-dyskinetic disorders when treated with metoclopramide.

With caution, prescribe the drug to elderly patients due to the frequent occurrence of parkinsonism.

neurological disorders.

Extrapyramidal disorders may occur, especially in children, and/or at high doses. These reactions are usually observed at the beginning of treatment and may occur after a single application. If extrapyramidal symptoms develop, metoclopramide should be discontinued immediately. In general, these effects disappear completely upon discontinuation of treatment, but may require symptomatic treatment (benzodiazepines in children and/or anticholinergic antiparkinsonian drugs in adults).

Between each administration of metoclopramide, even in the case of vomiting and dose rejection, at least a 6-hour interval must be observed to avoid overdose. Long-term treatment with metoclopramide can lead to tardive dyskinesia, which is potentially irreversible, especially in the elderly. Treatment should not be continued for more than 3 months due to the risk of tardive dyskinesia. Treatment should be discontinued if clinical signs of tardive dyskinesia appear.

Neuroleptic malignant syndrome has been reported with the use of metoclopramide in combination with neuroleptics, as well as with metoclopramide monotherapy. If symptoms of neuroleptic malignant syndrome occur, metoclopramide should be discontinued immediately and appropriate treatment instituted.

In patients with concomitant neurological diseases and in patients receiving treatment with other drugs acting on the central nervous system, it is necessary to be especially careful.

The use of metoclopramide may also increase the symptoms of Parkinson's disease.

Methemoglobinemia.

Cases of methemoglobinemia have been reported, which may be associated with a deficiency of NADH-cytochrome b5 reductase. In such cases, you should immediately permanently stop taking metoclopramide and take appropriate measures (for example, treatment with methylene blue).

Heart disorders.

Serious adverse reactions from the cardiovascular system have been reported, including cases of acute vascular insufficiency, severe bradycardia, cardiac arrest and prolongation of the QT interval, which were observed after taking metoclopramide in the form of injections, especially after administration.

The intravenous drug should be administered as a slow bolus injection (over at least 3 minutes) to reduce the risk of adverse reactions (eg, hypotension, akathisia).

Impaired kidney and liver function.

Dose reduction is recommended in patients with impaired renal function or severe hepatic impairment.

The drug should be used with caution in patients at risk, namely in elderly patients with cardiac conduction disorders, with uncorrected electrolyte imbalance or bradycardia, and patients taking other drugs that prolong the QT interval. The drug should not be used for the treatment of chronic diseases such as gastroparesis, dyspepsia and gastroesophageal reflux disease, or as an adjunct to surgical or radiological procedures.

Ampoules taken from the package should not be left in the sun for a long time.

Use during pregnancy or lactation.

Pregnancy.

A large amount of data on pregnant women (more than 1000 results from the use of the drug) indicates the absence of any toxicity that leads to malformations or fetotoxicity. Metoclopramide can be used during pregnancy if clinically necessary. Due to the pharmacological properties (as with other neuroleptics), in the case of the use of metoclopramide at the end of pregnancy, the appearance of extrapyramidal syndrome in the newborn cannot be excluded. It is necessary to avoid the use of metoclopramide in the final stages of pregnancy. When using metoclopramide, you need to monitor the newborn.

Lactation.

Metoclopramide passes into breast milk in small amounts. Therefore, it is not recommended to use metoclopramide during breastfeeding. Consideration should be given to discontinuing metoclopramide in women who are breastfeeding.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.

When using the drug, you should refrain from potentially hazardous activities that require increased attention (driving vehicles, working with other mechanisms).

Dosage and administration

The solution for injection is administered intramuscularly or intravenously as a slow bolus injection over at least 3 minutes.

As a solvent, use 0.9% sodium chloride solution, 5% glucose solution.

Adults.

The drug is prescribed at a dose of 10 mg up to 3 times a day. The maximum daily dose is 30 mg or 0.5 mg/kg of body weight.

The use of injectable forms should be carried out for the shortest possible period of time with the fastest possible transition to the use of oral or rectal forms of metoclopramide.

Children.

When used to prevent postoperative nausea and vomiting, metoclopramide should be used after surgery.

The recommended dose of metoclopramide is 0.1-0.15 mg/kg body weight up to 3 times a day. The maximum daily dose is 0.5 mg/kg of body weight. If it is necessary to continue the use of the medicinal product, at least 6-hour intervals should be observed.

Dosing scheme.

Age, years	Body weight, kg	Single dose, mg	Frequency
			Up to 3 times a day
			Up to 3 times a day
			Up to 3 times a day
			Up to 3 times a day
			Up to 3 times a day

The maximum duration of use of metoclopramide for the treatment of established postoperative nausea and vomiting is 48 hours.

The maximum duration of the use of metoclopramide to prevent delayed nausea and vomiting caused by chemotherapy is 5 days.

Patients with impaired renal function

In patients with end-stage renal dysfunction (creatinine clearance ≤15 ml / min), the dose of metoclopramide should be reduced by 75%.

In patients with moderate to severe renal impairment (creatinine clearance 15–60 ml/min), the dose of metoclopramide should be reduced by 50%.

Patients with liver failure due to an increase in the half-life, use half the dose.

Elderly patients.

Consideration should be given to reducing the dose in elderly patients due to age-related decline in renal and hepatic function.

duration of treatment.

In order to minimize the risks of adverse reactions from the nervous system and other adverse reactions, the drug should be used only for short-term treatment (up to 5 days).

Children.

Metoclopramide is contraindicated in children under the age of 1 year.

Overdose

Symptoms: drowsiness, decreased level of consciousness, confusion, irritability, anxiety and its increase, convulsions, extrapyramidal-motor disorders, dysfunction of the cardiovascular system with bradycardia and an increase or decrease in blood pressure, hallucinations, respiratory and cardiac arrest, dystonic reactions. Isolated cases of methemoglobinemia have been reported.

Adverse reactions

From the gastrointestinal tract: nausea, dyspepsia, dry mouth, constipation. When using metoclopramide in doses exceeding the daily dose, diarrhea may occur in patients.

From the nervous system:

; extrapyramidal reactions, usually dystonia (including very rarely cases of dyskinetic syndrome), especially in children and patients under the age of 30, the risk of which increases when the daily dose of 0.5 mg / kg of body weight is exceeded: facial muscle spasm, trismus, rhythmic protrusion of the tongue, bulbar type of speech, spasm of extraocular muscles, including oculogeric crises, involuntary spasmodic movements, in particular in the head, neck and shoulders, tonic blepharospasm, unnatural positions of the head and shoulders, opisthotonus, muscle hypertonicity;
parkinsonism (tremor, muscle twitching, bradykinesia, muscle rigidity, akinesia, mask-like face) after long-term treatment with metoclopramide in some elderly patients, as well as in renal failure;
tardive dyskinesia, which may be irreversible, may occur during long-term therapy with metoclopramide, mainly in elderly patients (especially women), in patients with diabetes mellitus and usually develops after discontinuation of the drug. Manifested by involuntary movements of the tongue, face, mouth, jaw, sometimes involuntary movements of the trunk and / or limbs;
neuroleptic malignant syndrome, including hyperpyrexia, altered consciousness, muscle rigidity, dysfunction of the autonomic nervous system and elevated serum creatine phosphokinase levels. This syndrome is potentially lethal, if it occurs, metoclopramide should be stopped immediately and treatment should be started urgently (dantrolene, bromocriptine);
fever, headache, dizziness, drowsiness, fatigue, asthenia, fatigue, depressed consciousness, fear, anxiety, confusion, tinnitus, akathisia.

There is also a risk of acute (short-term) neurological disorders, which is higher in children.

From the side of the psyche: depression, hallucinations, confusion, anxiety, restlessness.

From the side of the cardiovascular system: bradycardia, especially with intravenous use, cardiac arrest within a short time after injection, which may be due to bradycardia, atrioventricular block, sinus node block, especially with intravenous use, QT interval prolongation, supraventricular premature beats, ventricular premature beats, ventricular torsades de pointes , arterial hypotension, shock, syncope when administered intravenously, acute arterial hypertension in patients with pheochromocytoma.

Separate reports have been registered on the possibility of developing severe cardiovascular reactions due to the use of metoclopramide, especially when administered intravenously.

From the blood and lymphatic system: methemoglobinemia, which may be associated with a deficiency of NADH-cytochrome-b5-reductase, especially in infants, sulfhemoglobinemia, which is associated mainly with the concomitant use of high doses of drugs that release sulfur.

From the immune system: hypersensitivity reactions including anaphylactic reactions, including angioedema, anaphylactic shock. Due to the presence of sodium sulfite in the dosage form, there may be isolated cases of hypersensitivity reactions, especially in patients with bronchial asthma, in the form of nausea, vomiting, wheezing, acute asthma attack, impaired consciousness or shock. These reactions may have an individual course.

From the skin and subcutaneous tissue: hypersensitivity reactions, including: skin rashes, flushing and itching of the skin, urticaria.

From the reproductive system and the function of the mammary glands: after longer drug therapy, due to stimulation of prolactin secretion, hyperprolactinemia, gynecomastia, galactorrhea or menstrual disorders, amenorrhea may occur; with the development of these phenomena, the use of metoclopramide should be discontinued.

Laboratory indicators: increased levels of liver enzymes.

In adolescents and patients with severely impaired renal function (renal failure), as a result of which the excretion of metoclopramide slows down, the development of side effects is especially closely monitored. In case of their occurrence, the use of the drug should be stopped immediately.

The risk of developing adverse reactions from the nervous system increases with the use of the drug in high doses and with prolonged use.

Best before date

Storage conditions

Keep out of the reach of children in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Incompatibility. Metoclopramide injection solution must not be mixed with alkaline infusion solutions.

Package

2 ml in an ampoule; 5 ampoules in a blister pack; 1 or 2 blister packs in a pack.

Manufacturer

PJSC “Pharmaceutical firm “Darnitsa”.

Location of the manufacturer and its address of the place of business.

Ukraine, 02093, Kyiv, st. Borispolskaya, 13.

Compound

One ampoule (2 ml solution) contains - active substancewa: metoclopramide hydrochloride - 10 mg; Excipients: sodium chloride, sodium sulfite anhydrous E 221, disodium edetate, propylene glycol, hydrochloric acid, water for injection.

Description

Transparent colorless liquid.

Pharmacotherapeutic group

Means for the treatment of functional disorders of the gastrointestinal tract; prokinetics.
ATX code: A03FA01.

Pharmacological properties

Pharmacodynamics
Antiemetic, helps to reduce nausea, hiccups; stimulates the peristalsis of the upper gastrointestinal tract. The antiemetic effect is due to the blockade of dopamine receptors and an increase in the excitation threshold of the trigger zone chemoreceptors. Metoclopramide is believed to inhibit dopamine-induced relaxation of gastric smooth muscle, thus enhancing the cholinergic responses of gastrointestinal smooth muscle. Helps accelerate gastric emptying by preventing relaxation of the body of the stomach and increasing the phase activity of the antrum. In this case, the relaxation of the upper sections of the small intestine occurs, which leads to an improvement in the coordination of the peristalsis of the body and the antrum of the stomach and upper sections of the small intestine. Reduces the reflux of contents into the esophagus by increasing the pressure of the lower esophageal sphincter at rest and increases the clearance of acid from the esophagus by increasing the amplitude of its peristaltic contractions.
Metoclopramide stimulates prolactin secretion and causes a transient increase in circulating aldosterone levels, which may be accompanied by transient fluid retention.
Pharmacokinetics
Protein binding is about 30%. Passes through the placental barrier and the blood-brain barrier, penetrates into breast milk. The effect begins to develop 10-15 minutes after intramuscular injection and 1-3 minutes after intravenous administration. T½ - 3 - 5 hours, in case of impaired renal function - up to 14 hours. The drug is excreted mainly through the kidneys (85% within 72 hours) unchanged and in the form of sulfate and glucuronide conjugates.
In children, the pharmacodynamics of metoclopramide after intravenous administration is very variable and a clear “concentration-effect” relationship has not been established in them. Although the pharmacokinetics of metoclopramide has been studied in children with chemotherapy-induced nausea and vomiting, there is insufficient data to conclude that the pharmacokinetics of metoclopramide in adults and children coincide. The elimination half-life of metoclopramide in neonates (aged 3.5 weeks) after the first and tenth doses was significantly longer (23.1 and 10.3 hours, respectively) compared with children of other age groups due to reduced clearance. This may be due to age-related immaturity of liver and kidney function at birth. The mean half-life of metoclopramide in children of other age groups was 4.1-4.5 hours (range 1.7 to 12.5 hours).
In patients with renal insufficiency, the clearance of metoclopramide decreases in proportion to the decrease in creatinine clearance, while its half-life increases. However, in this group of patients, the pharmacokinetics of metoclopramide remain linear. Due to the reduced clearance of metoclopramide in this group of patients, the maintenance dose of metoclopramide should be reduced to avoid accumulation. In severe renal insufficiency, the clearance of metoclopramide is reduced by 70%, and the elimination half-life increases to 10 hours (with creatinine clearance 10–50 ml / min) and 15 hours (with creatinine clearance less than 10 ml / min).
In patients with impaired liver function (cirrhosis), metoclopramide may accumulate, associated with a decrease in its clearance by 50%.
Data on the pharmacokinetics of the solution after administration to the elderly are not available. It is possible to change the pharmacokinetic parameters associated with age-related changes in liver and kidney function.

Indications for use

Adults. For the prevention of postoperative nausea and vomiting.
For the symptomatic treatment of nausea and vomiting, including nausea and vomiting in acute migraine.
For the prevention of nausea and vomiting induced by radiation therapy.
The injection course of treatment should be as short as possible. The patient should be transferred to the oral or rectal route of administration as soon as possible.
Children aged 1 to 18 years. For the prevention of delayed (non-acute) nausea and vomiting associated with chemotherapy, as a second-line drug. The maximum course of treatment is 5 days.
For the treatment of established postoperative nausea and vomiting, as a second-line drug. The maximum course of treatment is 48 hours.

Contraindications

Hypersensitivity to metoclopramide or drug components, gastrointestinal bleeding, pyloric stenosis, mechanical intestinal obstruction, perforation of the stomach or intestines, 3-4 days after operations on the stomach and / or intestines, pheochromocytoma (confirmed or suspected, due to the risk of severe hypertensive complications), Parkinson's disease, extrapyramidal disorders (including a history of neuroleptic or metoclopramide-induced tardative dyskinesia), epilepsy, prolactin-dependent tumors, episodes of methemoglobinemia in a history of taking metoclopramide or with a deficiency of NADP-cytochrome-b5, simultaneous use of levodopa or dopamine stimulants receptors, pregnancy, children under 1 year of age, lactation.
Due to the content of sodium sulfite, metoclopramide solution should not be administered to patients with bronchial asthma with hypersensitivity to sulfite.

Dosage and administration

The maximum duration of the drug use is not more than 5 days!
The solution for injection is administered intramuscularly or intravenously as a bolus for at least 3 minutes. Adults at a dose of 10 mg up to 3 times a day (the maximum single dose is 10 mg, the maximum daily dose is 30 mg or 0.5 mg / kg).
Children. The dose is calculated in accordance with the table or based on the calculation of 0.10 - 0.15 mg / kg of body weight up to 3 times a day. The maximum daily dose is 0.5 mg/kg of body weight.

The maximum duration of therapy is 5 days. With repeated vomiting, the minimum interval between injections of metoclopramide should not be less than 6 hours.
With reduced kidney function, the drug is prescribed:
- with creatinine clearance less than 15 ml / min - in doses reduced by 75%;
- with creatinine clearance from 15 to 60 ml / min - in doses reduced by 50%.
In severe hepatic impairment, the dose of metoclopramide should be reduced by 50%.
For elderly patients, dosing is carried out taking into account changes in liver and kidney function, as indicated above.

Side effect

From the digestive system: at the beginning of treatment, constipation, diarrhea are possible; rarely - dry mouth.
From the side of the central nervous system: at the beginning of treatment, fatigue, drowsiness, dizziness, headache, depression, akathisia are possible; infrequently - dystonia, impaired consciousness, rarely - convulsions (especially in patients with epilepsy), the frequency is unknown - tardive dyskinesia, which may be permanent, during or after long-term treatment (especially in elderly patients), neuroleptic malignant syndrome. With prolonged use, more often in elderly patients, the phenomena of parkinsonism, dyskinesia are possible.
Mental disorders: rarely - hallucinations.
From the hematopoietic and lymphatic systems: at the beginning of treatment, agranulocytosis is possible, the frequency is unknown - methemoglobinemia, which may be associated with a deficiency of NADP-cytochrome-b5-reductase, especially in newborns; sulfhemoglobinemia due to sulfur-containing substances in the composition of the drug (mainly with the concomitant use of high doses of drugs containing sulfur).
From the side of the heart: rarely - bradycardia, the frequency is unknown - cardiac arrest (occurs shortly after injection, and may be due to bradycardia); atrioventricular blockade, blockade of the sinus node (especially with intravenous administration); prolongation of the QT interval; arrhythmia by type torsade de pointes.
From the vascular side: often - hypotension, especially with intravenous administration, the frequency is unknown - shock, syncope after injection, acute arterial hypertension in patients with pheochromocytoma.
From the endocrine system: rarely, with prolonged use in high doses - hyperprolactinemia and associated amenorrhea, galactorrhea, gynecomastia, menstrual disorders.
General disorders: often - asthenia.
From the immune system: rarely - hypersensitivity reactions, the frequency is unknown - anaphylactic reactions (including anaphylactic shock, especially when administered intravenously).
Allergic reactions: rarely - skin rash.
The following reactions occur most frequently when high doses of metoclopramide are used: extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia (even after a single dose of the drug, especially in children and young people); drowsiness, impaired consciousness, hallucinations.

Precautionary measures

During the period of treatment with the drug, you can not drink alcohol and alcohol-containing drugs.
Caution should be used in bronchial asthma, arterial hypertension, hepatic and / or renal insufficiency, in old age, early childhood (increased risk of dyskinetic syndrome).
neurological disorders. Extrapyramidal disorders are more likely to occur in children or when prescribing the drug in high doses. As a rule, they occur at the beginning of therapy, even with a single administration of the drug. These disorders are completely reversible and, if they occur, it is necessary to immediately stop the administration of metoclopramide. In severe cases, the administration of benzodiazepines (in children) or anticholinergic antiparkinsonian drugs (in adults) may be required to reduce extrapyramidal disorders.
To reduce the risk of overdose, the time interval between injections should not be less than 6 hours.
Long-term treatment with metoclopramide can lead to the development of irreversible tardative dyskinesia. In order to prevent this complication, the duration of treatment should not exceed 3 months. When the first symptoms of tardative dyskinesia appear, the administration of metoclopramide should be stopped immediately. When administered in combination with neuroleptics (very rarely - in the form of monotherapy), metoclopramide can provoke the development of neuroleptic malignant syndrome. In this case, the introduction of metoclopramide should also be immediately stopped and its treatment should be started.
Metoclopramide may exacerbate parkinsonism.
Methemoglobinemia. Although there have been no reports of metoclopramide provoking episodes of methemoglobinemia, if it develops (especially in individuals with a deficiency of NADP-cytochrome-b5), its administration should be stopped and methylene blue should be started.
Cardiovascular pathology. There are isolated cases of occurrence after intravenous administration of metoclopramide of cardiovascular insufficiency, severe bradycardia (up to cardiac arrest), prolongation of the QT interval. This should be taken into account when intravenous administration of metoclopramide, especially in patients with risk factors (persons with prolongation of the QT interval, uncompensated electrolyte imbalance, bradycardia and taking concomitant drugs that affect repolarization). To reduce the risk of cardiovascular complications, the dose of metoclopramide should be administered over at least 3 minutes.
The drug contains sodium sulfite as excipients, which in rare cases can provoke the occurrence of severe allergic reactions, bronchospasm.
The solution contains a small amount (less than 1 mmol per dose) of sodium ions, which should be taken into account when administered to young children.
Peculiarities of application in pediatric and geriatric practice
Metoclopramide is contraindicated in children under 1 year of age. Since the pharmacodynamics of metoclopramide after oral and intravenous administration is variable in children, and a clear concentration-effect relationship has not been established.
Adolescents and young people (15-19 years old), as well as the elderly, have an increased risk of extrapyramidal reactions during treatment with metoclopramide.
Treatment with metoclopramide for more than 5 days should be avoided in all cases, except when it is assumed that the therapeutic effect outweighs the risk of developing tardive dyskinesia.

Use during pregnancy and lactation

Contraindicated for use during pregnancy. There is evidence that the use of metoclopramide during pregnancy does not cause congenital disorders or fetotoxic changes. However, its use can be justified only as a last resort, since the development of extrapyramidal syndrome in a child after birth is not excluded. You should refrain from using metoclopramide in the last weeks of pregnancy, neonatal monitoring should be carried out if it is prescribed during pregnancy.
When used during lactation (breastfeeding), it should be borne in mind that metoclopramide passes into breast milk. Despite the fact that the level of metoclopramide in milk is low, its effect on the child in this case cannot be excluded. Consideration should be given to stopping breastfeeding if metoclopramide is needed.

Influence on the ability to drive vehicles and control mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions due to the risk of drowsiness, dizziness, dystonia and dyskinesia, as well as impaired visual reactions.

Interaction with other drugs

Contraindicated combinations. The drug is not prescribed simultaneously with levodopa drugs or dopamine receptor stimulants (antagonism with metoclopramide).
Combinations to avoid. Alcohol enhances the sedative effect of metoclopramide.
Combinations to consider when prescribing metoclopsramida. Due to the prokinetic action of metoclopramide, the absorption of some drugs may be altered.
Anticholinergics and morphine enhance the inhibitory effect of metoclopramide on gastrointestinal motility.
CNS depressants (morphine and its derivatives, tranquilizers, sedatives, antihistamines, antidepressants, barbiturates and clonidine) mutually enhance the effect when used with metoclopramide.
Antipsychotics increase the risk of extrapyramidal disorders. Taking metoclopramide together with antidepressants from the group of serotonin reuptake blockers increases the risk of serotonin syndrome.
Metoclopramide reduces the bioavailability of digoxin, and monitoring of plasma concentrations of digoxin is required.
The drug enhances the absorption of tetracycline, ampicillin, paracetamol, acetylsalicylic acid, levodopa, ethanol, cyclosporine (maximum concentration by 46%, exposure - by 22%, which requires monitoring the concentration of cyclosporine); reduces the absorption of cimetidine.
When administered against the background of the use of mivacuronium and suxamethonium, it can increase the duration of muscle relaxation (due to blockade of cholinesterase). The action of metoclopramide can be weakened by cholinesterase inhibitors.
Strong inhibitors of CYP2D6 (fluoxetine and paroxetine) may increase the effect of metoclopramide (although the clinical significance of this is not yet clear).
Metoclopramide solution is pharmaceutically (physically and chemically) compatible (up to 48 hours) with solutions of cimetidine, mannitol, potassium acetate and potassium phosphate; physically compatible (up to 48 hours) with solutions of ascorbic acid, benztropine mesylate, cytarabine, dexamethasone sodium phosphate, diphenhydramine, doxorubicin, sodium heparin, sodium hydrocortisone phosphate, lidocaine hydrochloride, multivitamin solutions (if stored in a refrigerator), solutions of B vitamins with ascorbic acid.
Solutions of metoclopramide are physically compatible up to 24 hours (do not use if precipitation is observed) with clindamycin phosphate, cyclophosphamide, insulin. Conditionally compatible (use within one hour after mixing or can be infused directly into the same venous line) with ampicillin sodium, cisplatin, erythromycin lactobionate, sodium methotrexate, potassium benzylpenicillin, tetracycline hydrochloride. Incompatible (not compatible) with sodium cephalothin, sodium chloramphenicol, sodium bicarbonate.

Metoclopramide hydrochloride (metoclopramide)

Composition and form of release of the drug

Tablets white or white with a yellowish tint, with a chamfer, marbling is allowed.

Excipients: lactose monohydrate 60 mg, potato starch "Extra" 28.47 mg, 0.53 mg, calcium stearate 1 mg.

10 pieces. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (5) - packs of cardboard.

pharmachologic effect

Means, helps to reduce nausea, hiccups; stimulates peristalsis of the gastrointestinal tract. The antiemetic effect is due to the blockade of dopamine D 2 receptors and an increase in the threshold of the trigger zone chemoreceptors; it is a blocker of serotonin receptors. Metoclopramide is thought to inhibit dopamine-induced relaxation of gastric smooth muscle, thus enhancing cholinergic responses in GI smooth muscle. Promotes faster gastric emptying by preventing relaxation of the body of the stomach and increasing the activity of the antrum and upper small intestine. It reduces the reflux of contents into the esophagus by increasing the pressure of the esophageal sphincter at rest and increases the clearance of acid from the esophagus by increasing the amplitude of its peristaltic contractions.

Metoclopramide stimulates prolactin secretion and causes a transient increase in circulating aldosterone levels, which may be accompanied by transient fluid retention.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Protein binding is about 30%. Biotransformed in the liver. It is excreted mainly by the kidneys both unchanged and as metabolites. T 1/2 is from 4 to 6 hours.

Indications

Vomiting, nausea, hiccups of various origins. Atony and hypotension of the stomach and intestines (including postoperative); biliary dyskinesia; reflux esophagitis; flatulence; as part of the complex therapy of exacerbations of peptic ulcer of the stomach and duodenum; acceleration of peristalsis during radiopaque studies of the gastrointestinal tract.

Contraindications

Bleeding from the gastrointestinal tract, mechanical intestinal obstruction, perforation of the stomach or intestines, pheochromocytoma, extrapyramidal disorders, epilepsy, prolactin-dependent tumors, glaucoma, pregnancy, lactation, simultaneous use of anticholinergic drugs, hypersensitivity to metoclopramide.

Dosage

Adults inside - 5-10 mg 3-4 times / day. With vomiting, severe nausea, metoclopramide is administered intramuscularly or intravenously at a dose of 10 mg. Intranasally - 10-20 mg in each nostril 2-3 times / day.

Maximum doses: single when taken orally - 20 mg; daily - 60 mg (for all methods of administration).

The average single dose for children over 6 years of age is 5 mg 1-3 times / day orally or parenterally. For children under 6 years of age, the daily dose for parenteral administration is 0.5-1 mg / kg, the frequency of administration is 1-3 times / day.

Side effects

From the digestive system: at the beginning of treatment, constipation, diarrhea are possible; rarely - dry mouth.

From the side of the central nervous system: at the beginning of treatment, a feeling of fatigue, drowsiness, dizziness, headache, depression, akathisia are possible. Extrapyramidal symptoms may occur in children and young people (even after a single use of metoclopramide): spasm of the facial muscles, hyperkinesis, spastic torticollis (usually disappear immediately after stopping metoclopramide). With prolonged use, more often in elderly patients, the phenomena of parkinsonism, dyskinesia are possible.

From the hematopoietic system: at the beginning of treatment, agranulocytosis is possible.

From the endocrine system: rarely, with prolonged use in high doses - galactorrhea, gynecomastia, menstrual disorders.

Allergic reactions: rarely - skin rash.

drug interaction

With simultaneous use with anticholinergics, mutual weakening of the effects is possible.

With simultaneous use with neuroleptics (especially the phenothiazine series and butyrophenone derivatives), the risk of extrapyramidal reactions increases.

With simultaneous use, absorption of paracetamol, ethanol is enhanced.

Metoclopramide, when administered intravenously, increases the rate of absorption of diazepam and increases its maximum plasma concentration.

With simultaneous use with a slowly dissolving dosage form of digoxin, a decrease in the concentration of digoxin in the blood serum by 1/3 is possible. With simultaneous use with in a liquid dosage form or in the form of an instant dosage form, no interaction was noted.

With simultaneous use with zopiclone, absorption is accelerated; with cabergoline - a decrease in the effectiveness of cabergoline is possible; with ketoprofen - the bioavailability of ketoprofen decreases.

Due to antagonism against dopamine receptors, metoclopramide can reduce the antiparkinsonian effect of levodopa, while it is possible to increase the bioavailability of levodopa due to the acceleration of its evacuation from the stomach under the influence of metoclopramide. The results of the interaction are ambiguous.

With simultaneous use with mexiletin, the absorption of mexiletin is accelerated; with mefloquine - the rate of absorption of mefloquine and its concentration in blood plasma increase, while it is possible to reduce its side effects.

With simultaneous use with morphine, the absorption of morphine when taken orally is accelerated and its sedative effect is enhanced.

With simultaneous use with nitrofurantoin, the absorption of nitrofurantoin decreases.

When using metoclopramide immediately before the introduction of propofol or thiopental, it may be necessary to reduce their induction doses.

In patients receiving metoclopramide, the effects of suxamethonium chloride are enhanced and prolonged.

With simultaneous use with tolterodine, the effectiveness of metoclopramide decreases; with fluvoxamine - a case of the development of extrapyramidal disorders is described; with fluoxetine - there is a risk of developing extrapyramidal disorders; with cyclosporine - the absorption of cyclosporine increases and its concentration in the blood plasma increases.

special instructions

Use with caution in patients with bronchial asthma, arterial hypertension, impaired liver and / or kidney function, with Parkinson's disease.

With extreme caution should be used in children, especially young children, because. they have a significantly higher risk of developing dyskinetic syndrome. Metoclopramide in some cases may be effective for vomiting caused by cytotoxic drugs.

Against the background of the use of metoclopramide, distortions of the data of laboratory indicators of liver function and the determination of the concentration of aldosterone and prolactin in the blood plasma are possible.

Influence on the ability to drive vehicles and control mechanisms

During the treatment period, potentially hazardous activities that require increased attention, rapid psychomotor reactions should be avoided.

Pregnancy and lactation

Contraindicated for use during pregnancy.

When used during lactation (breastfeeding), it should be borne in mind that metoclopramide passes into breast milk.

Use in the elderly

When used in elderly patients, it must be borne in mind that with long-term use of metoclopramide in high or medium doses, the most common side effects are extrapyramidal disorders, especially parkinsonism and tardive dyskinesia.

Description

Tablets of white or almost white color, with a facet, marbling is allowed.

Compound

Each tablet contains: active substance- metoclopramide hydrochloride - 10 mg; Excipients- lactose monohydrate, potato starch, povidone, calcium stearate.

Pharmacotherapeutic group

Means for the treatment of functional disorders of the gastrointestinal tract. Prokinetics.
ATX code: A03FA01.

Pharmacological properties

Indications for use

Adults. For the prevention of delayed (non-acute) nausea and vomiting associated with chemotherapy; for the prevention of nausea and vomiting induced by radiation therapy; for the symptomatic treatment of nausea and vomiting, including nausea and vomiting in acute migraine. Metoclopramide can be used in combination with oral analgesics to improve their absorption in acute migraine.
Children aged 1 to 18 years. For the prevention of delayed (non-acute) nausea and vomiting associated with chemotherapy as a second-line drug.

Contraindications

Gastrointestinal bleeding, pyloric stenosis, mechanical intestinal obstruction, perforation of the stomach or intestines, the first 3-4 days after operations on the stomach and / or intestines, pheochromocytoma, extrapyramidal disorders, epilepsy, prolactin-dependent tumors, pregnancy, children under 1 year of age, period lactation, hypersensitivity to metoclopramide or drug components, tardive dyskinesia due to a history of taking neuroleptics or metoclopramide, Parkinson's disease, simultaneous use with levodopa or dopamine receptor agonists, methemoglobinemia associated with the use of metoclopramide or a history of NADH-cytochrome b5 reductase deficiency in history .

Dosage and administration

Metoclopramide should be taken 30 minutes before a meal, the tablets are swallowed without chewing, washed down with a small amount of water.
The required minimum interval between doses should be 6 hours, even in case of loss of the drug due to vomiting.
The maximum duration of the drug use is not more than 5 days!
The dose is determined individually depending on the clinical symptoms and age of the patient. The maximum daily dose is not more than 0.5 mg/kg of body weight. The usual adult dose is 10 mg up to three times daily.
Children
Metoclopramide is contraindicated in children under 1 year of age due to an increased risk of extrapyramidal disorders. For children aged 1–18 years weighing less than 60 kg, the recommended dose of metoclopramide is 0.1–0.15 mg/kg body weight up to three times a day. For this category of patients, it is recommended to use metoclopramide in dosage forms with the possibility of ensuring appropriate dosing. Children aged 15-18 years: weighing more than 60 kg, the drug is used at a dose of 10 mg up to three times a day.
Elderly patients
Consideration should be given to reducing the dose in elderly patients due to age-related decline in renal and hepatic function.
Impaired kidney function
In patients with end-stage renal disease (creatinine clearance ≤ 15 ml / min), the dose of metoclopramide should be reduced by 75%. In moderate to severe renal insufficiency (creatinine clearance 15-60 ml / min), the dose of metoclopramide should be reduced by 50%.
Impaired liver function
In patients with severe hepatic impairment, the dose of metoclopramide should be reduced by 50%.
If it is necessary to use metoclopramide in a single dose of less than 10 mg, it is recommended to use dosage forms with the ability to ensure appropriate dosing.

Precautionary measures

Use with caution in bronchial asthma, arterial hypertension, Parkinson's disease, hepatic and / or renal insufficiency, in old age.
During the period of treatment with metoclopramide, you should not drink alcohol and alcohol-containing drugs.
Peculiarities of application in pediatric and geriatric practice
Adolescents and young people (15-19 years old), as well as the elderly, have an increased risk of extrapyramidal reactions during treatment with metoclopramide.
Treatment with metoclopramide for more than 5 days should be avoided in all cases, except when it is assumed that the therapeutic effect outweighs the risk of developing tardive dyskinesia.
Neurological disorders
Extrapyramidal disorders are more likely to occur in children or when prescribing the drug in high doses. These disorders are completely reversible and, if they occur, metoclopramide should be stopped immediately.
To reduce the risk of overdose, the interval between doses should not be less than 6 hours.
Long-term treatment with metoclopramide can lead to the development of irreversible tardive dyskinesia. In order to prevent this complication, the duration of treatment should not exceed 3 months. When the first symptoms of tardive dyskinesia appear, metoclopramide should be stopped immediately. When taken in combination with neuroleptics (very rarely - in the form of monotherapy), metoclopramide can provoke the development of neuroleptic malignant syndrome. In this case, metoclopramide should also be stopped immediately and treatment started.
Metoclopramide may exacerbate parkinsonism.
Methemoglobinemia
Although there have been no reports of metoclopramide provoking episodes of methemoglobinemia, if it develops (especially in individuals with a deficiency of NADH-cytochrome-b5-reductase), its administration should be stopped and methylene blue should be started.
Cardiovascular pathology
Given the very rare reports of serious cardiovascular adverse reactions associated with the use of metoclopramide, especially when administered intravenously, special care is needed when using metoclopramide in patients with an increased risk of developing cardiovascular complications, including elderly patients with impaired cardiac conduction. , electrolyte balance or bradycardia, or using other drugs that prolong the QT interval.
Due to the lactose content, the drug is not recommended for patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Use during pregnancy and lactation

Metoclopramide is contraindicated in pregnancy. Metoclopramide passes into breast milk, so when taking it, it is necessary to wean the baby from the breast.
AT experimental studies no adverse effect of metoclopramide on the fetus has been established.

Influence on the ability to drive vehicles and mechanisms

Metoclopramide can cause drowsiness, dizziness, dyskinesia and dystonia, and therefore affect vision, as well as the ability to drive vehicles or operate machines. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

Side effect

Adverse reactions are presented in accordance with the classification of organ systems and the frequency of occurrence: very often (≥ 1/10), often (≥ 1/100 to< 1/10), нечасто (≥ 1/1000 до < 1/100), редко (≥ 1/10000 до < 1/1000), очень редко (< 1/10000), частота неизвестна (не может быть оценена на основе имеющихся данных).
From the digestive system: at the beginning of treatment, constipation, diarrhea are possible; rarely - dry mouth.
From the side of the central nervous system: at the beginning of treatment, a feeling of fatigue, drowsiness, dizziness, headache, depression, akathisia are possible; infrequently - dystonia, impaired consciousness; rarely - convulsions (especially in patients with epilepsy); frequency unknown - tardive dyskinesia, which may be permanent, during or after long-term treatment (especially in elderly patients), neuroleptic malignant syndrome. With prolonged use, more often in elderly patients, the phenomena of parkinsonism, dyskinesia are possible.
tardive dyskinesia. After taking metoclopramide, elderly patients, especially women, may experience dyskinesias (lip biting, cheek puffing, fast or worm-like movements of the tongue, uncontrolled chewing movements, uncontrolled movements of the arms and legs), often irreversible. Such symptoms appear, as a rule, after long-term continuous treatment with metoclopramide, less often during short-term treatment with smaller doses of the drug. Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms may resolve or improve upon discontinuation of metoclopramide treatment.
Allergic reactions: rarely - skin rash.
Mental disorders: often - depression; infrequently - hallucinations; rarely - confusion.
From the endocrine system: infrequently - hyperprolactinemia.
General disorders: often - asthenia.
From the hematopoietic and lymphatic systems: at the beginning of treatment, agranulocytosis is possible; rarely - galactorrhea (with prolonged use in high doses), gynecomastia, menstrual disorders; frequency unknown - methemoglobinemia, which may be associated with a deficiency of NADH-cytochrome-b5-reductase, especially in newborns, sulfhemoglobinemia, which is associated mainly with the concomitant use of high doses of drugs that release sulfur.
From the side of the heart: rarely - bradycardia; frequency unknown - cardiac arrest (occurs shortly after injection and may be due to bradycardia), atrioventricular block, sinus node block (especially with intravenous administration), prolongation of the QT interval, arrhythmia by type torsade de pointes.
From the vascular side: often - hypotension, especially when administered intravenously; frequency unknown - shock, syncope after injection, acute arterial hypertension in patients with pheochromocytoma.
From the immune system: rarely - hypersensitivity reactions; the frequency is unknown - anaphylactic reactions (including anaphylactic shock, especially when administered intravenously).
The following reactions occur most frequently when high doses of metoclopramide are used: extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia (even after taking a single dose of the drug, especially in children and young people); drowsiness, impaired consciousness, hallucinations.
Treatment with metoclopramide may cause extrapyramidal symptoms in the form of violations of muscle tone, involuntary movements of the limbs, spasms of the mimic muscles of the face and torticollis. The appearance of such symptoms can occur at therapeutic doses in any age group, but most often in children and young people, as well as after the use of metoclopramide at higher doses used to prevent vomiting, due to antitumor chemotherapy. Dystonic reactions usually resolve within 24 to 48 hours after discontinuation of metoclopramide.

Interaction with other drugs

Contraindicated combinations
The drug is not prescribed simultaneously with levodopa drugs or dopamine receptor stimulants.
Combinations to avoid
Alcohol enhances the sedative effect of metoclopramide.
Combinations to consider when prescribing metoclopramide
Due to the use of metoclopramide, the absorption of some drugs may be altered.
Anticholinergics and morphine enhance the inhibitory effect of metoclopramide on gastrointestinal motility.
CNS depressants (morphine and its derivatives, tranquilizers, sedatives, antihistamines, antidepressants, barbiturates and clonidine) mutually enhance the effect when used with metoclopramide.
Antipsychotics increase the risk of extrapyramidal disorders. Taking metoclopramide together with antidepressants from the group of serotonin reuptake blockers increases the risk of serotonin syndrome.
Metoclopramide reduces the bioavailability of digoxin, and monitoring of plasma concentrations of digoxin is required.
The drug enhances the absorption of tetracycline, ampicillin, paracetamol, acetylsalicylic acid, levodopa, ethanol, cyclosporine (maximum concentration by 46%, exposure - by 22%, which requires monitoring the concentration of cyclosporine), reduces the absorption of cimetidine.
When administered against the background of the use of mivacuronium and suxamethonium, it can increase the duration of muscle relaxation (due to blockade of cholinesterase). The action of metoclopramide can be weakened by cholinesterase inhibitors.
Strong inhibitors of CYP2D6 (fluoxetine and paroxetine) may increase the effect of metoclopramide (although the clinical significance of this is not yet clear).

Overdose

Symptoms: extrapyramidal disorders, hypersomnia, changes in consciousness, confusion and hallucinations, dysfunction of the cardiovascular system with bradycardia and cardiac arrest, increased or decreased blood pressure, disorientation.
Symptoms persist 24 hours after ingestion.
Treatment: in case of extrapyramidal symptoms associated or not associated with overdose, treatment is symptomatic only (benzodiazepines in children and / or anticholinergic antiparkinsonian drugs in adults).
Symptomatic treatment and continuous monitoring of the state of cardiovascular and respiratory function in accordance with the clinical condition of the patient.

Package

10 tablets in a blister pack made of PVC film and aluminum foil. 1 or 5 blister packs, together with the leaflet, are placed in a pack of cardboard (No. 10x1, No. 10x5).