Metoclopramide

Instruction manual

For medical use of the drug

Structure:

Active ingredient: megoclopramide hydrochloride;

1 ml of the drug contains 5 mg of metoclopramide hydrochloride (in terms of 100% anhydrous substance);

excipients: sodium sulfite anhydrous (E 221), disodium edetate, sodium chloride, water for injection.

Dosage form.

Injection.

Basic physical and chemical properties: transparent, colorless liquid.

Pharmacotherapeutic group.

Means that affect the digestive system and metabolism. peristalsis stimulants. code atx a03f a01.

Pharmacological properties.

Pharmacodynamics

A specific blocker of dopamine (D2) and serotonin (5-HT3) receptors, inhibits the chemoreceptors of the trigger zone of the brain stem, weakens the sensitivity of visceral nerves that transmit impulses from the pylorus and duodenum to the vomiting center. Through the hypothalamus and the parasympathetic nervous system (innervation of the gastrointestinal tract), it has a regulatory and coordinating effect on the tone and motor activity of the digestive system. Increases the tone of the stomach and intestines, accelerates the emptying of the stomach, reduces pseudocidal stasis, prevents pyloric and esophageal reflux, stimulates intestinal motility. It normalizes the separation of bile, reduces the spasm of the sphincter of Oddi, without changing its tone, eliminates dyskinesia of the gallbladder. Stimulates the secretion of prolactin (like other dopamine receptor blockers).

Pharmacokinetics

The onset of action on the gastrointestinal tract is observed 10-15 minutes after intramuscular injection and 1-3 minutes after intravenous administration, manifested by accelerated evacuation of the contents of the stomach (approximately 3 hours) and antiemetic effect (lasts 12 hours). With parenteral administration, it is rapidly and completely absorbed. It is slightly metabolized in the liver by binding to sulfuric and glucuronic acids. The elimination half-life makes 2,5-6 hours. About 85% of the dose is excreted in the urine unchanged or in the form of metabolites within 72 hours, the other part - with feces. In patients with impaired renal function, the elimination half-life is increased. It easily penetrates the blood-brain and placental barriers, as well as into breast milk.

Clinical characteristics.

Indications.

Adults

• Prevention of postoperative nausea and vomiting.
• Symptomatic treatment of nausea and vomiting, including those associated with acute migraine.
• Prevention of nausea and vomiting caused by radiotherapy.

Children.

• As a second-line drug to prevent delayed nausea and vomiting caused by chemotherapy.
• As a second-line drug for the treatment of existing postoperative nausea and vomiting.

Contraindications

• Hypersensitivity to metoclopramide or to any other components of the drug; gastrointestinal bleeding; mechanical intestinal obstruction; gastrointestinal perforation; confirmed or suspected pheochromocytoma due to the risk of severe attacks of arterial hypertension; history of tardive dyskinesia due to antipsychotics or metoclopramide; epilepsy (increased frequency and intensity of seizures); Parkinsons disease; simultaneous use with levodopa or dopaminergic agonists; established methemoglobinemia with the use of metoclopramide or a history of nadn-cytochrome b5 reductase deficiency; prolactin-dependent tumors; increased convulsive readiness (ektirapiramidnye movement 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 pay attention to.

When used with oral medicinal products, such as paracetamol, metoclopramide hydrochloride may affect their absorption due to the effect of metoclopramide on gastric motility.

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

Inhibitors of the central nervous system (morphine derivatives, antipsychotics, sedative antihistamine blockers of H1 receptors sedative antidepressants, barbiturates, clonidine and similar drugs): potentiate the effect of metoclopramide.

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

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

Digoxin: Metoclopramide may decrease the bioavailability of digoxin. It is necessary to carefully monitor the concentration of digoxin in the blood plasma.

Cyclosporin: metoclopramide increases the bioavailability of cyclosporin (Cmax by 46% and effect by 22%). It is necessary to carefully monitor the concentration of cyclosporine in blood plasma. The clinical consequences of this phenomenon have not been definitively determined.

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

Powerful CYP2D6 inhibitors: exposure levels of metoclopramide increase while it is used with strong CYP2D6 inhibitors, 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 the action of succinylcholine.

Tricyclic antidepressants, monoamine oxidase inhibitors (MAOs), sympathomimetic drugs: metoclopramide may affect their effect.

Thiamine (Vitamin B): due to the content of metoclopramide sodium sulfite in the injection solution, simultaneous administration can lead to the rapid breakdown of thiamine in the body.

Features of the application.

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

2 ml of Metoclopramide hydrochloride solution contain less than 1 mmol (23 mg) of sodium.

Neurological disorders. Extrapyramidal disorders may occur, especially in children, and / or when using high doses. These reactions are usually observed at the beginning of treatment and can occur after a single application. In the event of the development of extrapyramidal symptoms, metoclopramide should be withdrawn immediately. In general, these effects completely disappear after 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 case of vomiting and dose rejection, in order to avoid overdose, it is necessary to observe at least a 6-hour interval.

Long-term treatment with metoclopramide can lead to tardive dyskinesia, which is irreversible, especially in the elderly. Treatment should not be continued for more than 3 months because of the risk of developing tardive dyskinesia. Treatment should be discontinued if clinical signs of tardive dyskinesia appear.

With the use of metoclopramide in combination with antipsychotics, as well as with monotherapy with metoclopramide, the development of malignant antipsychotic syndrome has been reported. In case of symptoms of a malignant antipsychotic syndrome, the use of metoclopramide should be stopped immediately and appropriate treatment should be started.

Use metoclopramide with caution in patients with concomitant neurological diseases and in patients receiving treatment with other drugs acting on the central nervous system.

When using metoclopramide, the symptoms of Parkinsons disease may also intensify.

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

Heart disorders. Severe adverse reactions from the cardiovascular system, 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 intravenous administration, were reported. Metoclopramide should be used with particular care, especially when the drug is administered intravenously, to elderly patients, patients with impaired cardiac conduction (including prolongation of the QT interval), patients with impaired electrolyte balance, bradycardia, as well as patients taking drugs that extend the QT interval. Intravenously, the drug should be administered by slow bolus injection (for at least 3 minutes) to reduce the risk of adverse reactions (eg, hypotension, akathisia).

Impaired renal and hepatic function. In patients with impaired renal function or severely impaired liver function, a dose reduction is recommended.

It should be used with caution in patients at risk, namely: elderly patients, patients with cardiac conduction disorders, with arterial hypertension, diabetes mellitus, with a history of depression (only if the expected benefit exceeds potential risks), with an uncorrected electrolyte imbalance or bradycardia, and patients taking drugs that prolong the QT interval.

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

If nausea, vomiting continues during treatment with metoclopramide, the possibility of cerebral disorders must be excluded.

The drug should not be prescribed after operations on the gastrointestinal tract (pyloroplasty or intestinal anastomosis), since vigorous muscle contractions interfere with the healing of sutures.

The drug contains sodium sulfite, so it can not be prescribed to patients with asthma with increased sensitivity to sulfite.

Ineffective with vomiting of vestibular origin.

Use during pregnancy or lactation.

Clinical studies indicate a lack of toxicity, leading to malformations or fetotoxicity. metoclopramide can be used during pregnancy, if there is a clinical need. due to pharmacological properties (like other antipsychotics) in the case of metoclopramide in the final stages of pregnancy, the appearance of extrapyramidal syndrome in a newborn cannot be ruled out. it is necessary to avoid the use of metoclopramide in the final stages of pregnancy. when using metoclopramide, you need to observe the newborn.

Metoclopramide in small amounts passes into breast milk.Therefore, it is not recommended to use metoclopramide during breastfeeding. It is necessary to consider the possibility of discontinuing the use of metoclopramide in women who are breastfeeding.

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

Metoclopramide can cause drowsiness, dizziness, dyskinesia, and dystonia, which can affect vision, as well as the ability to drive vehicles or other automated systems.

Dosage and administration.

The injection is administered intramuscularly or slowly intravenously. metoclopramide for intravenous administration should be used as a slow bolus injection for at least 3 minutes.

Adults

To prevent postoperative nausea and vomiting, the recommended single dose of metoclopramide is 10 mg. For the symptomatic treatment of nausea and vomiting, including those associated with acute migraine, as well as to prevent nausea and vomiting caused by radiotherapy, the recommended single dose of metoclopramide is 10 mg up to 3 times a day. The maximum recommended daily dose is 30 mg or 0.5 mg / kg body weight. The use of injection forms should occur within the shortest possible period of time with the most rapid 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 body weight. If necessary, continue the use of the drug, the interval between doses should be at least 6 hours.

Dosage schedule

The maximum duration of metoclopramide for the treatment of established postoperative nausea and vomiting is 48 hours. The maximum duration of metoclopramide to prevent delayed nausea and vomiting caused by chemotherapy is 5 days.

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

Patients with end-stage renal impairment (creatinine clearance

Patients with clinically severe hepatic insufficiency due to an increase in half-life should first be prescribed a half dose, the subsequent dose depends on the individual reaction to metoclopramide.

Children.

Metoclopramide hydrochloride, injection, is contraindicated in children under 1 year old.

Overdose.

Symptoms: drowsiness, decreased consciousness, confusion, irritability, hallucinations, disorientation, motor anxiety, cramps, extrapyramidal motor disorders, dystonic reactions, impaired cardiovascular function with bradycardia, increased or decreased blood pressure, respiratory arrest and cardiac activity . may develop methemoglobinemia, especially in children.

Treatment: in the event of the development of extrapyramidal symptoms, whether or not associated with an overdose, only symptomatic treatment is carried out (benzodiazepines in children and / or anticholinergic antiparkinsonian drugs in adults). In accordance with the clinical condition, it is necessary to carry out symptomatic treatment and constant monitoring of the functions of the cardiovascular and respiratory system.

Adverse Reactions

Immune system: hypersensitivity reactions, anaphylactic reactions (including anaphylactic shock, especially when administered intravenously), bronchospasm, especially in patients with a history of bronchial asthma.

Blood system and lymphatic system: methemoglobinemia, which may be associated with deficiency of NADH-cytochrome-b5 reductase, especially in infants, sulfhemoglobinemia, associated mainly with the concomitant use of high doses of sulfur-releasing drugs.

Cardiovascular system: bradycardia, especially when administered intravenously, cardiac arrest for a short time after injection, which may be a consequence of bradycardia, atrioventricular block, sinus node blockage, especially when administered intravenously, QT interval prolongation, ventricular tachycardia of the “pirouette” type ,