Instructions for use Metoclopramide-Darnitsa solution for injection 5 mg/ml ampoule 2 ml No. 10
Composition
active ingredient: metoclopramide;
1 ml of solution contains metoclopramide hydrochloride 5 mg;
Excipients: sodium chloride, disodium edetate, anhydrous sodium sulfite (E 221), propylene glycol, diluted hydrochloric acid, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear colorless liquid.
Pharmacotherapeutic group
Peristalsis stimulants (propulsants).
ATX code A03F A01.
Pharmacological properties
Pharmacodynamics.
Metoclopramide is a central dopamine antagonist that also exhibits 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 point of the brain stem (chemoreceptors - the activating zone of the vomiting center), presumably through inhibition of dopaminergic neurons.
The increase in peristalsis is also partly controlled by higher centers, but the peripheral mechanism of action may also be partially involved, together with the activation of postganglionic cholinergic receptors and, possibly, the 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: it increases the tone of the stomach and intestines, accelerates gastric emptying, reduces gastrostasis, prevents pyloric and esophageal reflux, stimulates intestinal peristalsis. It normalizes bile secretion, reduces spasm of the sphincter of Oddi without changing its tone, and eliminates gallbladder dyskinesia.
Undesirable effects mainly extend to extrapyramidal symptoms, which are based on the mechanism of dopamine receptor-blocking action on the central nervous system.
Long-term treatment with metoclopramide may cause an increase in serum prolactin concentrations due to the lack of dopaminergic inhibition of prolactin secretion. Galactorrhea and menstrual irregularities have been reported in women, and gynecomastia in men. However, these symptoms resolved after discontinuation of treatment.
Pharmacokinetics.
In the case of intravenous administration, metoclopramide is rapidly distributed.
The onset of action on the gastrointestinal tract is noted 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 blood plasma proteins. The volume of distribution is 2.2–3.4 l/kg of body weight. It is metabolized in the liver. The half-life is 2.6–4.6 hours in healthy volunteers and approximately 14 hours in patients with renal failure. It penetrates the blood-brain and placental barriers, is excreted in breast milk. Part of the dose (approximately 20%) is excreted in its original form, and the rest (approximately 80%) after metabolic transformations in the liver is excreted by the kidneys together with urine in compounds with glucuronic or sulfuric acid.
In patients with severe renal impairment, creatinine clearance is reduced by up to 70% and the plasma elimination half-life is increased (approximately 10 hours for creatinine clearance 10–50 ml/min and 15 hours for creatinine clearance < 10 ml/min).
In patients with liver cirrhosis, accumulation of metoclopramide was observed, accompanied by a 50% decrease in plasma clearance.
Indication
For adults: prevention of postoperative nausea and vomiting; nausea and vomiting induced by radiotherapy; symptomatic treatment of nausea and vomiting, including those associated with acute migraine.
For children: as a second-line drug for the prevention of delayed chemotherapy-induced nausea and vomiting; treatment of postoperative nausea and vomiting.
Contraindication
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);
history of tardive dyskinesia caused by neuroleptics or metoclopramide;
epilepsy (increased frequency and intensity of seizures);
Parkinson's disease;
concomitant use with levodopa or dopaminergic agonists;
established methemoglobinemia with metoclopramide or a history of NADH-cytochrome-b5-reductase deficiency;
prolactin-dependent tumors;
increased seizure readiness (extrapyramidal movement disorders);
patient's age up to 1 year (due to the risk of developing extrapyramidal disorders).
Due to the content of sodium sulfite, the drug should not be prescribed to patients with bronchial asthma with hypersensitivity to sulfite.
Interaction with other medicinal products 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.
When used concomitantly with oral medications, such as paracetamol, metoclopramide may affect their absorption due to its effect on 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 antihistamines-H1 receptor blockers, sedative antidepressants, barbiturates, clonidine and related drugs): potentiate the sedative effect of metoclopramide.
Neuroleptics: when metoclopramide is used in combination with other neuroleptics, 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 serotonin syndrome.
Digoxin: Metoclopramide may reduce the bioavailability of digoxin. Close monitoring of digoxin plasma concentrations is necessary.
Cyclosporine: Metoclopramide increases the bioavailability of cyclosporine (Cmax by 46% and exposure by 22%). Close monitoring of cyclosporine plasma concentrations is necessary. The clinical consequences of this phenomenon have not been definitively determined.
Mivacurium and suxamethonium: Metoclopramide injection may prolong the duration of neuromuscular block (due to inhibition of plasma cholinesterase).
Potent CYP2D6 inhibitors: Metoclopramide exposure levels are increased when co-administered with potent CYP2D6 inhibitors, such as fluoxetine and paroxetine. Although the clinical significance of this is not known, patients should be monitored for adverse reactions.
Metoclopramide may prolong the action of succinylcholine.
Due to the content of sodium sulfite in the injection solution, thiamine (vitamin B1) taken simultaneously with metoclopramide can be rapidly broken down in the body.
Application features
Metoclopramide-Darnitsa, solution for injection contains sodium: 1 ml of solution for injection contains less than 1 mmol (23 mg) of sodium, i.e. this medicinal product is essentially sodium-free.
Ampoules removed from the packaging should not be left in the sun for a long time.
Neurological disorders.
Extrapyramidal disorders may occur, especially in children and/or when high doses are used. These reactions are usually observed at the beginning of treatment and may occur after a single administration. In the event of extrapyramidal symptoms, metoclopramide should be discontinued immediately. These effects generally disappear completely after discontinuation of treatment, but may require symptomatic treatment (benzodiazepines in children and/or anticholinergic antiparkinsonian drugs in adults).
An interval of at least 6 hours must be observed between each administration of metoclopramide, even in the event of vomiting and rejection of the dose, to avoid overdose.
Long-term treatment with metoclopramide may lead to tardive dyskinesia, which is potentially irreversible, especially in the elderly. Treatment should not exceed 3 months due to the risk of developing tardive dyskinesia. Treatment should be discontinued if clinical signs of tardive dyskinesia appear (see section "Adverse reactions").
When using metoclopramide in combination with neuroleptics, as well as with metoclopramide monotherapy, the development of neuroleptic malignant syndrome has been reported. If symptoms of neuroleptic malignant syndrome occur, metoclopramide should be discontinued immediately and appropriate treatment should be initiated.
Particular caution should be exercised when treating patients with concomitant neurological diseases and patients receiving other drugs that act on the central nervous system (see section "Contraindications").
Metoclopramide may also worsen symptoms of Parkinson's disease.
Methemoglobinemia.
Cases of methemoglobinemia, which may be associated with NADH-cytochrome b5-reductase deficiency, have been reported. In such cases, metoclopramide should be immediately and permanently discontinued and appropriate measures should be taken (e.g. treatment with methylene blue).
Heart disorders.
Severe cardiovascular adverse reactions, including cases of acute vascular insufficiency, severe bradycardia, cardiac arrest and QT prolongation, have been reported following the administration of metoclopramide by injection, most commonly following intravenous administration (see section 4.8).
Particular caution is required when metoclopramide is administered intravenously to elderly patients, patients with cardiac conduction disorders (including QT prolongation), patients with electrolyte imbalance, bradycardia, and patients taking drugs that prolong the QT interval. Intravenously, the drug should be administered by slow bolus injection (minimum 3 minutes) to reduce the risk of adverse reactions (e.g. hypotension, akathisia).
Impaired kidney and liver function.
The drug should not be used to treat chronic diseases such as gastroparesis, dyspepsia and gastroesophageal reflux disease, or as an adjunct to surgical or radiological procedures.
The drug contains sodium sulfite, which in some cases may cause severe hypersensitivity reactions and bronchospasm.
Use during pregnancy or breastfeeding
Pregnancy: A large amount of data on pregnant women (more than 1000 outcomes from the use of the medicinal product) indicate the absence of any toxicity leading to malformations or feto/neonatal toxicity. Metoclopramide can be used during pregnancy if there is a clinical need. Due to its pharmacological properties (as with other neuroleptics), the occurrence of extrapyramidal syndrome in the newborn cannot be excluded when metoclopramide is used in late pregnancy. The use of metoclopramide in late pregnancy should be avoided. The newborn should be observed when metoclopramide is used.
Breastfeeding. Metoclopramide is excreted in small amounts in breast milk. Metoclopramide may affect the breastfed infant. Therefore, the use of metoclopramide during breast-feeding is not recommended. Discontinuation of metoclopramide should be considered in breast-feeding women.
Ability to influence reaction speed when driving vehicles or other mechanisms
Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonia, which may affect vision and the ability to drive or operate other automated systems.
Method of administration and doses
The solution for injection should be 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.
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 for the prevention of 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 injectable forms should be for the shortest possible period of time, with a transition to oral or rectal forms of metoclopramide as soon as possible.
For children.
When used to prevent postoperative nausea and vomiting, metoclopramide should be used after the end of 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 it is necessary to continue using the drug, intervals of at least 6 hours should be observed.
Dosage regimen
| Age, years | Body weight, kg | Single 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 | >60 | 10 | 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 use of metoclopramide for the prevention of delayed nausea and vomiting caused by chemotherapy is 5 days.
Patients with renal impairment
In patients with end-stage renal disease (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
For patients with severe hepatic impairment, the dose of metoclopramide should be reduced by 50%.
Elderly patients.
Dose reduction should be considered in elderly patients due to age-related decline in renal and hepatic function.
Children.
Metoclopramide is contraindicated in children under 1 year of age.
Overdose
Symptoms: drowsiness, decreased level of consciousness, confusion, irritability, restlessness and its increase, convulsions, extrapyramidal motor disorders, cardiovascular dysfunction with bradycardia and increased or decreased blood pressure, hallucinations, respiratory and cardiac arrest, dystonic reactions. Isolated cases of methemoglobinemia have been reported.
Treatment: in the event of the development of extrapyramidal symptoms, whether or not related to overdose, only symptomatic treatment is provided (benzodiazepines for children and/or anticholinergic antiparkinsonian drugs for adults).
According to the clinical condition, symptomatic treatment and constant monitoring of the functions of the cardiovascular and respiratory systems should be carried out.
Side effects
Gastrointestinal: nausea, dyspepsia, dry mouth, constipation. When using metoclopramide in doses higher than the daily dose, patients may experience diarrhea.
From the nervous system:
extrapyramidal reactions, usually dystonia (including very rare cases of dyskinetic syndrome), especially in children and patients under 30 years of age, the risk of which increases when the daily dose of 0.5 mg/kg body weight is exceeded: facial muscle spasm, trismus, rhythmic protrusion of the tongue, bulbar type of speech, spasm of extraocular muscles, including oculogyric crises, involuntary spasmodic movements, particularly in the head, neck and shoulders, tonic blepharospasm, unnatural positions of the head and shoulders, opisthotonus, muscle hypertonia;
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 with long-term metoclopramide therapy, mainly in elderly patients (especially women), in patients with diabetes mellitus and usually develops after drug withdrawal. It is manifested by involuntary movements of the tongue, face, mouth, jaw, sometimes involuntary movements of the trunk and/or limbs;
neuroleptic malignant syndrome, which includes hyperpyrexia, altered consciousness, muscle rigidity, autonomic dysfunction, and elevated serum creatine phosphokinase. This syndrome is potentially fatal and should be treated immediately with metoclopramide (dantrolene, bromocriptine).
fever, headache, dizziness, drowsiness, feeling of fatigue, feeling of fear, confusion, asthenia, increased fatigue, depressed level of consciousness, tinnitus, akathisia.
There is also a risk of acute (short-term) neurological disorders, which is higher in children.
Psychiatric: depression, hallucinations, confusion, anxiety, restlessness.
Cardiovascular system: bradycardia, especially with intravenous administration, cardiac arrest for a short time after injection, which may be a consequence of bradycardia, atrioventricular block, sinus node block, especially with intravenous administration, QT interval prolongation, supraventricular extrasystole, ventricular extrasystole, torsades de pointes, hypotension, shock, syncope with intravenous administration, acute arterial hypertension in patients with pheochromocytoma.
There have been isolated reports of the possibility of severe cardiovascular reactions associated with the use of metoclopramide, especially when administered intravenously.
Blood and lymphatic system disorders: methemoglobinemia, which may be associated with NADH-cytochrome b5-reductase deficiency, especially in infants, sulfhemoglobinemia, which is mainly associated with concomitant use of high doses of sulfur-releasing drugs.
Immune system disorders: hypersensitivity reactions including anaphylactic reactions, including angioedema, anaphylactic shock. Due to the sodium sulfite content in the dosage form, isolated cases of hypersensitivity reactions may occur, 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.
Skin and subcutaneous tissue disorders: hypersensitivity reactions, including: skin rashes, hyperemia and itching of the skin, urticaria.
On the part of the reproductive system and mammary gland function: after longer-term therapy with the drug, due to stimulation of prolactin secretion, hyperprolactinemia, gynecomastia, galactorrhea or menstrual cycle disorders, amenorrhea may occur; if these phenomena develop, the use of metoclopramide should be discontinued.
Laboratory indicators: increased liver enzymes.
In adolescents and patients with severe renal impairment (renal failure), as a result of which the excretion of metoclopramide is impaired, the development of side effects should be monitored particularly closely. If they occur, the use of the drug should be discontinued immediately.
The risk of developing adverse reactions from the nervous system increases when using the drug in high doses and with prolonged use.
Expiration date
4 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 ° C. Do not freeze.
Incompatibility
Metoclopramide injection solution should not be mixed with alkaline infusion solutions.
Metoclopramide-Darnitsa, solution for injection, is incompatible with the following drugs: chloramphenicol, cisplatin, erythromycin, furosemide, calcium gluconate, methotrexate, sodium bicarbonate, penicillin G.
Packaging
2 ml in an ampoule; 5 ampoules in a contour blister pack, 1 or 2 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
Address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
