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

*Active substance:*
Metoclopramide hydrochloride monohydrate in terms of metoclopramide hydrochloride	- 5.00 mg
Excipients:
Disodium edetate dihydrate	- 0.10 mg
Sodium sulfite anhydrous	- 0.125 mg
Sodium chloride	- 9.00 mg
Sodium acetate trihydrate	- 0.54 mg
Acetic acid	- 0.00066 ml
Water for injections	- up to 1.0 ml

Description:Pa clear, colorless solution.

Pharmacotherapeutic group:Antiemetics - dopamine receptor blocker central

ATX: & nbsp

A.03.F.A Motility stimulators GIT

A.03.F.A.01 Metoclopramide

Pharmacodynamics:

Metoclopramide is 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) it has 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 in mowing). 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 affect the tone of the blood vessels of the brain, blood pressure, respiratory function, as well as kidney and liver, on hematopoiesis, 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 and the excretion of potassium ions.

Pharmacokinetics:

Binding to plasma proteins is approximately 30%. Passes through the placental barrier and the blood-brain barrier penetrates into breast milk. The effect begins to develop 10-15 min after intramuscular injection and 1-3 min after intravenous injection. T_1/2- 3-5 hours, with renal dysfunction - up to 14 hours. Removal of the drug occurs mainly through the kidneys (85% for 72 hours) in an unchanged form and in the form of sulfate and glucuronide conjugates.

Children pharmacodynamics of metoclopramide after intravenous administration is very variable and a clear "concentration-effect" ratio has not been established. Although the pharmacokinetics of metoclopramide have been studied in children with nausea and vomiting caused by chemotherapy, there is insufficient evidence to conclude that the pharmacokinetics of metoclopramide coincide in adults and children.The half-life of metoclopramide in newborn infants (at the age of 3.5 weeks) after the first and tenth dose was significantly higher (23.1 and 10.3 hours, respectively) compared with children of other age groups due to lower clearance. This may be due to the age-related immaturity of the liver and kidney function at birth. The average half-life of metoclopramide in children of other age groups is 4.1-4.5 hours (range of vibrations from 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 the period of its half-elimination increases. Nevertheless, this group of patients retains the linearity of the pharmacokinetics of metoclopramide. Due to a decrease in the clearance of metoclopramide in this group of papists, a maintenance dose of metoclopramide should be reduced to avoid its cumulation. In severe renal failure, the clearance of metoclopramide decreases to 10 hours (with creatinine clearance of 10-50 ml / min) and 15 hours (with creatinine clearance less than 10 ml / min).

In patients with impaired liver function (cirrhosis) It is possible to accumulate metoclopramide, which is associated with a 50% decrease in its clearance.

Data on the pharmacokinetics of the solution after administration older persons are absent. Possible changes in pharmacokinetic parameters associated with age-related changes in liver and kidney function.

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 and chemotherapy.

To enhance peristalsis in radiocontrast studies of the gastrointestinal tract.

Children aged 1 to 18 years

The second line of treatment for postoperative nausea and vomiting.

The second line of prevention of delayed nausea and vomiting caused by chemotherapy.

Contraindications:

- Hypersensitivity to metoclopramide or any of the components of the drug;

- gastrointestinal hemorrhage, mechanical intestinal obstruction, perforation of the wall of the stomach and intestines, 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 application with levodopa and agonists of dopamine receptors;

- methemoglobinemia due to taking metoclopramide or a deficiency of nicotinamide adenine dinucleotide (NADH) cytochrome b5 in the anamnesis;

- prolactinoma or prolactin-dependent tumor;

- children under 1 year;

- the period of breastfeeding;

- pregnancy (III trimester).

Carefully:

When used in elderly patients, impaired cardiac conduction (including lengthening of the interval QT), disturbance of water-electrolyte balance, bradycardia, with the use of other drugs that extend the interval QT, arterial hypertension, concomitant neurological diseases, when taking medications that affect the central nervous system, depression (in the anamnesis); renal insufficiency of moderate and severe severity (SC 15-60 ml / min); hepatic failure of severe severity; pregnancy (I-II trimesters).

Pregnancy and lactation:

Pregnancy

Metoclopramide can be used during pregnancy (I-II trimesters) only if the potential benefit to the mother exceeds the potential risk to the fetus.

In connection with the pharmacological features (like other neuroleptics) in the use of metoclopramide at the end of pregnancy, it is impossible to exclude the possibility of developing extrapyramidal symptoms in a newborn.

Breastfeeding period

Metoclopramide in small amounts excreted in breast milk. It is impossible to exclude the possibility of developing adverse reactions in the child. The use of metoclopramide during breastfeeding is contraindicated. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenous or intramuscular.

Intravenously, the drug should be administered bolus slowly (at least 3 minutes). To avoid an overdose, a minimum interval of 6 hours between administration of the drug should be observed.

Adults

Prevention of postoperative nausea and vomiting

The recommended single dose is 10 mg.

Symptomatic treatment of nausea and vomiting, including acute migraine

Prevention of nausea and vomiting caused by radiation therapy and chemotherapy

The recommended single dose of 10 mg is administered up to three times a day.

To enhance peristalsis in radiopaque studies of the gastrointestinal tract

Intravenous bolus slow administration of 10-20 mg is recommended 10 minutes before the start of the study.

The maximum daily dose is 30 mg or 0.5 mg / kg.

The period of administration of the drug in the form of an injection should be as short as possible, with a subsequent transition to a dosage form for oral administration.

Children aged 1 to 18 years

Intravenous bolus slow administration is recommended. The dose is calculated according to the table or based on a calculation of 0.10-0.15 mg / kg body weight up to 3 times a day. The maximum daily dose is 0.5 mg / kg body weight.

Age (years)	Weight, kg)	Dose (mg)	Frequency
1-3	10-14	1	Up to 3 times a day
3-5	15-19	2	Up to 3 times a day
5-9	20-29	2,5	Up to 3 times a day
9-18	30-60	5	Up to 3 times a day
15-18	More than 60	10	Up to 3 times a day

The maximum duration of metoclopramide for the prevention of postoperative nausea and vomiting is 2 days.

To prevent nausea and vomiting caused by chemotherapy - 5 days.

Elderly patients may need to reduce the dose due to a decrease in kidney and liver function.

In patients with terminal stage of renal failure (QC less than 15 ml / min), the daily dose should be reduced by 75%. In patients with moderate or severe renal insufficiency (KK 15-60 ml / min), the dose should be reduced by 50%.

In patients with hepatic insufficiency of severe severity, the dose should be reduced by 50%.

Side effects:

The incidence of adverse reactions is classified as follows: 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 (can not be estimated based on available data).

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

From the central nervous system: at the beginning of treatment, a feeling of fatigue, drowsiness, dizziness, headache, depression, asthenia, extrapyramidal disorders (especially in children and young patients and / or exceeding the recommended doses of the drug, even after a single injection), infrequent - dystonia, impaired consciousness; rarely - convulsions (especially in patients with epilepsy); frequency unknown - tardive dyskinesia, which can be permanent, during or after long-term treatment (especially in elderly patients), neuroleptic malignant syndrome.With prolonged use, more often in elderly patients, there may be phenomena of parkinsonism, dyskinesia.

Mental disorders: often - depression; infrequently - hallucinations; rarely confusion.

On the part of the hematopoiesis and lymphatic system: at the beginning of treatment, agranulocytosis is possible; the frequency is unknown - methemoglobinemia, which may be associated with a deficiency of the enzyme NADH-cytochrome b5-reductase, especially in newborns; sulfgemoglobinemia, caused by sulfur-containing substances in the preparation (mainly, with the concomitant use of high doses of drugs containing sulfur); leukopenia, neutropenia.

From the heart: rarely - bradycardia; frequency unknown - cardiac arrest, which can be caused by bradycardia; atrioventricular blockade, blockade of the sinus node (especially with intravenous administration), prolongation of the QT interval on the electrocardiogram, arrhythmia of the pirouette type (torsade de pointes).

From the side of the vessels: often - hypotension, especially with intravenous administration; frequency unknown - cardiogenic shock, fainting after injection, acute arterial hypertension in patients with pheochromocytoma.

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

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

From the immune system: infrequently - hypersensitivity; frequency unknown - anaphylactic reactions (including anaphylactic shock);

Allergic reactions: rarely - hives, maculopapular rash.

From the side of the kidneys and urinary tract: frequency unknown - polyuria, incontinence.

From the genitals and breast: unknown frequency - sexual dysfunction, priapism.

Undesirable reactions most frequently encountered with high doses of metoclopramide: extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia developed even after a single dose, especially in children and young patients (see section "Special instructions"); drowsiness, decreased level of consciousness, confusion, hallucinations.

Overdose:

Symptoms. Disorientation and extrapyramidal disorders, hypersomnia, drowsiness, altered consciousness,his confusion and hallucinations, irritability, dizziness, bradycardia, changes in blood pressure, cardiac and respiratory arrest, abdominal pain.

As a rule, the symptomatology disappears after stopping the drug within 24 hours.

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 cardiovascular and respiratory function are required depending on the clinical condition of the patient. There is no specific antidote.

Interaction:

Contraindicated combinations

Contraindicated concurrent use of metoclopramide with levodopa or dopamine receptor agonists, in connection with the existing mutual antagonism.

Combinations, which should be avoided

Alcohol increases the sedative effect of metoclopramide.

Combinations that require caution

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, H blockers₁-gistaminovyh receptors, 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.

With the concomitant use of metoclopramide and tetrabenazine, there is a possibility of a deficiency of dopamine, which can be accompanied by muscle spasm, difficulty in speaking or swallowing, anxiety, tremor, involuntary movements of muscles, including facial muscles.

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, while monitoring the concentration of digoxin in the blood plasma is required.

Metoclopramide enhances the absorption of tetracycline, ampicillin, paracetamol, acetylsalicylic acid, mexiletine, lithium, levodopa, ethanol and cyclosporine (C_maxby 46% and impact by 22%, which requires monitoring the concentration of cyclosporine in the blood plasma); reduces the absorption of cimetidine.

The exposure of metoclopramide increases with simultaneous use with potent inhibitors of isoenzyme CYP2D6, 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.

With the concomitant use of metoclopramide with atovahona, the concentration of atovahona in plasma is significantly reduced (about 50%). Concomitant use of metoclopramide with atovahona is not recommended.

With the concomitant use of metoclopramide with bromocriptine, the concentration of bromocriptine in the blood plasma increases.

The solution of metoclopramide 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, heparin sodium, hydrocortisone sodium phosphate, lidocaine hydrochloride, solutions of multivitamins (if stored in a refrigerator), solutions of B vitamins, with ascorbic acid.

The solution of metoclopramide is physically compatible up to 24 h (do not use if precipitation is observed) with clindamycin phosphate, cyclophosphamide, insulin.

Conditionally compatible (use within one hour after mixing or can be poured directly into the same venous line) with ampicillin sodium, cisplatinum, erythromycin lactobionate, sodium methotrexate, benzylpenicillin potassium, tetracycline hydrochloride.

Incompatible (do not combine!) With cephalothin sodium, chloramphenicol sodium, sodium bicarbonate.

Special instructions:

Metoclopramide is not effective in vomiting vestibular genesis.

In connection with the sodium sulfite content, the injectable solution of metoclopramide should not be prescribed to patients with bronchial asthma, with increased sensitivity to sulfites.

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.

Most side effects occur within 36 hours of the start of treatment and take place within 24 hours after withdrawal. Treatment should be, if possible, short-term.

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

Effect on the ability to drive transp. cf. and fur:

During the treatment period, it is necessary to refrain from driving vehicles, working with mechanisms and other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:RAsterol for intravenous and intramuscular administration, 5 mg / ml.

Packaging:

2 ml per ampoule of neutral glass.

For each ampoule paste a label of paper or lettering on the ampoule applied quickly fastening paint for glass products.

5 ampoules are placed in a contiguous cell pack of a polyvinylchloride (PVC) film or a polyethylene terephthalate (PET) film.

1 or 2 contour packs together with the instructions for use and the ampoule scarifier are placed in a cardboard pack.

5 or 10 ampoules together with the instruction for use and the ampoule ampoule are placed in a cardboard box with a corrugated liner.

When packing ampoules with a dot or a ring of fracture, the scarifier is not inserted.

Packing for hospitals. 4, 5 or 10 contour mesh packages together with an equal number of instructions for use are placed in a pack of cardboard for consumer containers.

50 or 100 contour mesh packages together with an equal number of instructions for use are placed in a box of corrugated cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004096

Date of registration:24.01.2017

Expiration Date:24.01.2022

The owner of the registration certificate:ELLARA, LTD. ELLARA, LTD. Russia

Manufacturer: & nbsp

ELLARA, LTD. Russia

Information update date: & nbsp24.02.2017

Illustrated instructions

Instructions

Metoclopramide (Metoclopramide)