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

Pharmacodynamics:A specific blocker of dopamine (D₂ ) and serotonin (5-HT₃) receptors, inhibits the chemoreceptors of the trigger zone of the brainstem, weakens the sensitivity of the visceral nerves that transmit impulses from the pyloric and duodenum to the vomiting center.Through the hypothalamus and the parasympathetic nervous system (innervation of the gastrointestinal tract (GI tract)) has a regulating and coordinating effect on the tone and motor activity of the upper gastrointestinal tract (including the tone of the lower sphincter of the esophagus). Increases the tone of the stomach and intestines, accelerates the emptying of the stomach, reduces the hyperacid stasis, prevents pyloric and esophageal reflux, stimulates intestinal peristalsis. Normalizes the separation of bile, reduces the spasm of the sphincter of Oddi. Without changing its tone, it eliminates dyskinesia of the gallbladder. Does not possess M-holinoblokiruyuschim, antihistamine, antiserotoninovym and ganglioblokiruyutsim action; does not affect the tone of the blood vessels of the brain, blood pressure, respiratory function, as well as kidney and liver, on the blood, gastric and pancreatic secretion. Stimulates the secretion of prolactin. Increases the sensitivity of tissues to acetylcholine (the action does not depend on vagal innervation, but is eliminated by holinoblokatorami). Stimulating the secretion of aldosterone, enhances the retention of sodium ions (Na⁺ ) and excretion of potassium ions (K⁺).

Pharmacokinetics:

The onset of action on the gastrointestinal tract is noted 1-3 minutes after intravenous (iv) injection and 10-15 minutes after intramuscular (IM) administration and is manifested by accelerating the evacuation of the stomach contents and antiemetic effect.

It is metabolized in the liver. Removal of the drug occurs mainly through the kidneys for 24-72 hours (85% of the dose), 30% unchanged. Easily penetrates through placental and blood-brain barrier, excreted in breast milk.

Pharmacokinetics in special clinical cases

Impaired renal function

In patients with severe renal dysfunction, the clearance of metoclopramide is reduced by 70%, while the half-life of plasma is increased (approximately 10 hours with creatinine clearance of 10-50 ml / min and 15 hours with creatinine clearance <10 mL / min).

Impaired liver function

In patients with cirrhosis of the liver metoclopramide is accumulated, associated with a decrease in plasma clearance by 50%.

Indications:

Adults

Prevention of postoperative nausea and vomiting.

Symptomatic treatment of nausea and vomiting, including acute migraine. Prevention of nausea and vomiting caused by radiation therapy.

Children and teens

Treatment of postoperative nausea and vomiting - as a second-line therapy. Prophylaxis of delayed nausea and vomiting caused by chemotherapy - as second-line therapy.

Contraindications:

- Hypersensitivity to metoclopramide or other components of the drug;

- gastrointestinal hemorrhage, mechanical intestinal obstruction, perforation of the wall of the stomach or intestine, conditions in which stimulation of the peristalsis of the gastrointestinal tract represents a risk;

- confirmed or suspected pheochromocytoma in connection with the risk of developing severe arterial hypertension;

- tardive dyskinesia, which developed after treatment with neuroleptics or metoclopramide in history;

- Epilepsy (increased frequency and severity of seizures);

- Parkinson's disease;

- simultaneous administration with levodopa or agonists of dopaminergic receptors;

- Methemoglobinemia due to metoclopramide or nicotinamide adenine dinucleotide (NADH) deficiency of cytochrome b5 in history;

prolactin-dependent tumors;

- pregnancy (III trimester);

- the period of breastfeeding;

- Children's age up to 1 year.

Carefully:Childhood; elderly age; renal / hepatic impairment; bronchial asthma; impaired cardiac conduction (including QT interval prolongation); violation of water-electrolyte balance; bradycardia; simultaneous reception of other drugs that extend the QT interval; arterial hypertension; associated neurological diseases; simultaneous administration of drugs affecting the central nervous system; depression (history); pregnancy (I, II trimester).

Pregnancy and lactation:Metoclopramide contraindicated in the third trimester of pregnancy due to the risk of developing extrapyramidal disorders in newborns. When using metoclopramide, pregnant women should be monitored for newborns. Metoclopramide excreted in breast milk. It is not recommended to use metoclopramide during breastfeeding, if necessary, use of the drug should stop breastfeeding.

Dosing and Administration:

Intravenously (intravenously) or intramuscularly (in / m).

The recommended single dose in adults is 10 mg, the maximum daily dose is -30 mg. Children are administered in a dose of 0.1-0.15 mg / kg body weight,the maximum dose is 0.5 mg / kg of body weight per day.

Recommendations for the regimen of dosing in children are given in the table:

Age	Body mass	Dose	Frequency
1-3 years	10-14 kg	1 mg	up to 3 times a day
3-5 years	15-19 kg	2 mg	up to 3 times a day
5-9 years	20-29 kg	2.5 mg	up to 3 times a day
9-18 years old	30-60 kg	5 mg	up to 3 times a day
15-18 years old	more than 60 kg	10 mg	up to 3 times a day

The duration of the drug is no more than 5 days. The maximum duration of treatment for postoperative nausea and vomiting is 48 hours. The interval between administration of the drug is 6 hours.

Intravenous injections are administered slowly (for a minimum of 3 minutes) in order to reduce the risk of unwanted effects (eg, hypotension, akathisia).

Special patient groups

Elderly patients

Consideration should be given to reducing the dose, taking into account the kidney and liver function, as well as the general condition of the patient.

Impaired renal function

In patients with terminal stage of renal failure (creatinine clearance <15 ml / min), the daily dose should be reduced by 75%.

In patients with moderate or severe renal impairment (creatinine clearance 15-60 ml / min), the dose should be reduced by half.

Impaired liver function

In patients with severe impairment of liver function, the dose should be reduced by half.

Side effects:

The frequency of unwanted reactions is given in accordance with the classification: very often (≥ 1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); rarely (≥1/10000, <1/1000); very rarely (<1/10000); the frequency is unknown (the frequency can not be estimated from the available data).

Violations from the blood and lymphatic system: the frequency is unknown - methemoglobinemia, probably associated with a deficiency of the enzyme NADH-dependent cytochrome-b5 reductase (especially in newborns), sulfemoglobinemia (most often with the simultaneous use of high doses of sulfur-containing drugs).

Heart Disease: infrequently bradycardia; frequency unknown - cardiac arrest, which can be caused by bradycardia, atrioventricular block, blockade of the sinus node, prolongation of the QT interval on the electrocardiogram, arrhythmia of the "pirouette" type.

Vascular disorders: often - lowering blood pressure, the frequency is unknown - cardiogenic shock, acute increase in blood pressure in patients with pheochromocytoma.

Disorders from the endocrine system *: infrequently - amenorrhea, hyperprolactinemia; rarely - galactorrhea; frequency unknown - gynecomastia.

* Endocrine disorders during prolonged treatment are associated with hyperprolactinemia (amenorrhea, galactorrhea, gynecomastia).

Disorders from the gastrointestinal tract: often - diarrhea; rarely dry mouth.

Immune system disorders: infrequently - hypersensitivity reactions; frequency unknown - anaphylactic reactions (including anaphylactic shock).

Impaired nervous system: very often - drowsiness; frequent-extrapyramidal disorders (especially in children and young patients and / or when the recommended dosage is exceeded, even after a single dose), parkinsonism, akathisia; infrequently - dystonia, dyskinesia, impaired consciousness; rarely convulsions, especially in patients with epilepsy; frequency unknown - tardive dyskinesia, sometimes persistent, during or after long-term treatment, especially in elderly patients, malignant neuroleptic syndrome.

Disorders of the psyche: often - depression; infrequently - hallucinations; rarely confusion.

General disorders and disorders at the site of administration: often - asthenia.

Undesirable reactions, most common when using high doses of the drug:

- Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia developed even after single dose application, especially in children and young patients (see section "Special instructions"),

- Drowsiness, decreased level of consciousness, confusion, hallucinations.

Overdose:

Symptoms: extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucinations, cardiac arrest and respiration.

Treatment: In the case of developing extrapyramidal symptoms caused by overdose or for another reason, treatment is exceptionally symptomatic (benzodiazepines in children and / or anticholinergic antiparkinsonics in adults).

Symptomatic treatment and continuous monitoring of cardiac and respiratory function are required depending on the clinical condition of the patient.

Interaction:

Contraindicated combinations

Simultaneous use of metoclopramide with levodopa or antagonists of dopamine receptors is contraindicated in connection with the existing mutual antagonism.

Combinations to Avoid

Alcohol increases the sedative effect of metoclopramide.

Combinations that should be taken into account

In connection with the prokinetic effect of metoclopramide, absorption of certain drugs may be impaired.

M-holinoblokatory and derivatives of morphine have a mutual antagonism with metoclopramide in relation to the effect on peristalsis of the gastrointestinal tract. Drugs that depress the central nervous system (morphine derivatives, tranquilizers, H1-histamine receptor blockers, antidepressants with sedative effect, barbiturates, clonidine and other drugs of these groups) may enhance the sedation effect of metoclopramide.

Metoclopramide enhances the effect of neuroleptics on extrapyramidal symptoms.

The use of metoclopramide with serotonergic drugs, for example, with selective serotonin reuptake inhibitors, increases the risk of developing serotonin syndrome (serotonin intoxication).

Metoclopramide decreases the bioavailability of digoxin. It is necessary to monitor the concentration of digoxin in the blood plasma.

Metoclopramide increases the bioavailability of cyclosporine (Cmax by 46% and exposure by 22%). It is necessary to regularly monitor the concentration of cyclosporine in the blood plasma.The clinical consequences of this interaction are not established.

With the simultaneous administration of metoclopramide with suxamethonium, the duration of the neuromuscular blockade may increase (by inhibiting cholinesterase in the plasma).

The exposure of metoclopramide increases with simultaneous use with potent inhibitors of the CYP2D6 isoenzyme, for example, fluoxetine and paroxetine. Although the clinical significance of this interaction is not established, it is necessary to monitor the occurrence of adverse reactions in patients.

Metoclopramide increases the absorption of tetracycline, ampicillin, paracetamol, acetylsalicylic acid; slows the absorption of cimetidine.

Simultaneous use with drugs that have a central stimulating effect (for example, monoamine oxidase inhibitors and sympathomimetics) can lead to a change in their effect, which may require adjustment of dosages.

Special instructions:

It is not effective for vomiting of vestibular genesis.

Do not appoint after operations on the digestive tract (like pyloroplasty or anastomosis of the intestine), because vigorous muscle contractions prevent healing.

Against the background of the use of metoclopramide, there are possible distortions of these laboratory parameters of liver function and determination of the concentration of aldosterone and prolactin in plasma.

In the appointment of metoclopramide, more often in high doses, extrapyramidal disorders may develop, especially in children and young patients, even after the administration of a single dose.

Care must be taken when using in patients with concomitant neurological diseases and in patients taking drugs that affect the central nervous system.

When the drug is used, symptoms of Parkinson's disease can also be noted. There have been reports of the occurrence of methemoglobinemia, which could be caused by a deficiency of the enzyme NADH-dependent cytochrome-b5 reductase. In this case, the drug should be stopped immediately and appropriate measures taken.

There have been reports of severe cardiovascular side effects, including vascular insufficiency, severe bradycardia, cardiac arrest, and prolongation of the QT interval after metoclopramide administration.

Particular care should be taken when administering intravenously to patients with "weak sinus syndrome" or otherimpaired conduction of the heart muscle (including prolongation of the QT interval), elderly patients, patients with electrolyte balance disorders, bradycardia, and also with the use of drugs that extend the QT interval.

Most side effects occur within 36 hours of the start of treatment and disappear within 24 hours after cancellation. The course of treatment should be as short as possible.

During the treatment with the drug, alcohol is not recommended.

The sodium pyrosulfite included in the preparation in rare cases can cause serious hypersensitivity reactions and bronchospasm.

Effect on the ability to drive transp. cf. and fur:When taking the drug should be avoided potentially dangerous activities that require increased attention, rapid mental and motor reaction (vehicle management, etc.) due to the possible development of side effects such as dizziness, drowsiness, dyskinesia, dystonia.

Form release / dosage:Solution for intravenous and intramuscular injection 5 mg / ml.

Packaging:

2 ml into ampoules of colorless hydrolytic glass of class I with a coding strip in the form of a ring of yellow color.On the neck of the ampoule, a notch and a point of white color above it are marked at the fault site. 5 ampoules are placed in a contour mesh package.

On 1 contour acheikova packing together with the instruction on application place in a pack from a cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013299 / 02

Date of registration:21.11.2008

Expiration Date:Unlimited

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

POLPHARMA PHARMACEUTICAL WORKS, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp09.05.2018

Illustrated instructions

Instructions

Metoclopramide (Metoclopramide)