Instructions for use Metoclopramide-Darnitsa tablets 10 mg No. 50
Composition
active ingredient: metoclopramide;
1 tablet contains metoclopramide hydrochloride 10 mg;
excipients: potato starch, lactose monohydrate, microcrystalline cellulose, povidone, calcium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a yellowish tinge, flat-cylindrical shape, with a bevel.
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 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
After oral administration, the drug is rapidly and completely absorbed. Bioavailability is on average 60-80%. Only a small part of the administered dose of metoclopramide binds to blood plasma proteins. The volume of distribution ranges from 2.2 to 3.4 l/kg. The maximum concentration in blood plasma is reached after 30-120 minutes, on average - after 1 hour. The onset of action on the gastrointestinal tract is noted 20-40 minutes after oral administration.
The antiemetic effect persists for 12 hours. Metabolized in the liver. Penetrates through the blood-brain and placental barriers, into breast milk. The half-life is from 2.6 to 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.
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
In adults, metoclopramide is indicated for the prevention of nausea and vomiting induced by radiotherapy, delayed nausea and vomiting induced by chemotherapy, and for the symptomatic treatment of nausea and vomiting, including that associated with acute migraine (in combination with oral analgesics to improve their absorption).
In children, metoclopramide should only be used as a second-line drug to prevent delayed chemotherapy-induced nausea and vomiting.
Contraindication
Hypersensitivity to metoclopramide or 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; simultaneous use with levodopa or dopaminergic agonists; established methemoglobinemia when using metoclopramide or with a history of NADH-cytochrome-b5-reductase deficiency; prolactin-dependent tumors; increased convulsive readiness (extrapyramidal movement disorders).
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.
Combinations to pay attention to.
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 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 are not fully understood.
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 tablets may prolong the effects of succinylcholine.
Metoclopramide may affect the absorption of other substances. For example, it may slow down the absorption of cimetidine, accelerate the absorption of paracetamol, various antibiotics (in particular, tetracycline, pivampicillin), lithium. Simultaneous administration of metoclopramide tablets and lithium may cause an increase in plasma lithium levels.
Application features
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.
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 administration. If extrapyramidal symptoms develop, 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 case of vomiting with the removal of the drug dose along with vomit, 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.
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 is required in patients with concomitant neurological diseases and patients receiving treatment with other drugs acting on the central nervous system.
The use of metoclopramide may also worsen the 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.
Particular attention should be paid to the use of metoclopramide in elderly patients, patients with cardiac conduction disorders (including QT interval prolongation), patients with electrolyte imbalance, bradycardia, and patients taking medications that prolong the QT interval.
Impaired kidney and liver function.
Given the very rare reports of severe cardiovascular reactions associated with the use of metoclopramide, it should be used with particular caution in elderly patients, patients with cardiac conduction disorders, uncorrected electrolyte imbalance or bradycardia, and patients taking drugs that prolong the QT interval.
The medicine contains lactose, therefore it should not be administered to patients suffering from rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
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.
Use during pregnancy or breastfeeding
Pregnancy. A large amount of data from pregnant women (more than 1000 outcomes of drug use) indicate the absence of any toxicity leading to malformations or fetotoxicity. Metoclopramide can be used during pregnancy if there is a clinical need. Due to pharmacological properties (as with other neuroleptics) in case of use of metoclopramide in late pregnancy, the occurrence of extrapyramidal syndrome in the newborn cannot be excluded. The use of metoclopramide in late pregnancy should be avoided. The newborn should be observed when using metoclopramide.
Breastfeeding. Metoclopramide is excreted in breast milk in small amounts. Therefore, the use of metoclopramide during breast-feeding is not recommended. Discontinuation of metoclopramide use in breast-feeding women should be considered.
Method of administration and doses
Take orally before meals, without chewing, with sufficient liquid.
In order to minimize the risks of nervous system and other adverse reactions, metoclopramide should only be prescribed for short-term treatment (up to 5 days).
Adults.
The usual therapeutic dose of metoclopramide is 10 mg up to 3 times a day. The maximum daily dose is 30 mg or 0.5 mg/kg body weight. The maximum duration of metoclopramide use is 5 days.
Children.
The recommended dose of metoclopramide for the prevention of delayed nausea and vomiting caused by chemotherapy 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.
Dosage regimen
| Body weight, kg | Single dose, mg | Frequency |
| 10-14 | 1 | up to 3 times a day |
| 15-19 | 2 | up to 3 times a day |
| 20-29 | 2.5 | up to 3 times a day |
| 30-60 | 5 | up to 3 times a day |
| > 60 | 10 | up to 3 times a day |
The maximum duration of metoclopramide use is 5 days.
Elderly patients.
Dose reduction should be considered in elderly patients due to age-related decline in renal and hepatic function.
Kidney dysfunction.
In patients with end-stage renal failure (creatinine clearance ≤ 15 ml/min), the dose of metoclopramide should be reduced by 75%.
In patients with moderate to severe renal insufficiency (creatinine clearance 15-60 ml/min), the dose of metoclopramide should be reduced by 50%.
Liver dysfunction.
Patients with severe hepatic insufficiency should use half the dose of metoclopramide.
Children
Metoclopramide is contraindicated in children under 1 year of age due to an increased risk of extrapyramidal disorders. For children weighing < 30 kg, metoclopramide should be used in dosage forms that allow for adequate dosing.
Overdose
Symptoms: drowsiness, depressed level of consciousness, confusion, irritability, restlessness and its increase, convulsions, extrapyramidal disorders, impaired function of the cardiovascular system with bradycardia and increased or decreased blood pressure, hallucinations, respiratory and cardiac arrest. Isolated cases of methemoglobinemia have been reported.
Treatment. In case of extrapyramidal symptoms associated with overdose, only symptomatic treatment is carried out (benzodiazepines - for children and/or anticholinergic antiparkinsonian drugs - for adults). In case of use of large doses of metoclopramide, it is necessary to remove it from the gastrointestinal tract by gastric lavage or taking activated charcoal and sodium sulfate.
According to the clinical condition, symptomatic treatment and constant monitoring of the functions of the cardiovascular and respiratory systems should be carried out.
Adverse reactions
Nervous system: dyskinetic syndrome, mainly in children (involuntary spasmodic movements, particularly in the head, neck and shoulders, tonic blepharospasm, spasm of the facial and masticatory muscles, deviation of the tongue, spasm of the pharyngeal muscles and tongue muscles, incorrect posture of the head and neck, overstrain of the spine, spasmodic flexion of the arms, spasmodic extension of the legs), headache, dizziness, increased fatigue, drowsiness, extrapyramidal disorders (which may occur even after a single dose, mainly in children and adolescents and/or when the recommended dose is exceeded), parkinsonism (tremor, muscle rigidity, akinesia), akathisia, dystonia, dyskinesia, depressed level of consciousness, tardive dyskinesia (which may be permanent during or after long-term treatment, especially in elderly patients), neuroleptic malignant syndrome (characteristic symptoms: fever, muscle rigidity, loss of consciousness, fluctuations in blood pressure, seizures (mainly in patients with epilepsy).
There is a risk of acute (short-term) neurological disorders, which is higher in children, and tardive dyskinesia in elderly patients. The risk of developing adverse reactions from the nervous system increases with the use of the drug in high doses and with prolonged treatment.
When using high doses, the following reactions occur more frequently (sometimes simultaneously):
Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia, even after a single dose of the drug, especially in children; drowsiness, depressed level of consciousness, confusion, hallucinations.
On the part of the psyche: asthenia, depression, hallucinations, confusion, anxiety, restlessness, confusion, tinnitus.
Cardiovascular system: bradycardia, atrioventricular block, sinus node block, QT prolongation, torsades de pointes, hypotension, shock, syncope, acute hypertension in patients with pheochromocytoma.
Blood and lymphatic system disorders: methemoglobinemia, which may be associated with NADH-cytochrome b5-reductase deficiency, especially in infants, sulfhemoglobinemia, mainly associated with concomitant use of high doses of sulfur-releasing drugs.
Immune system disorders: hypersensitivity reactions including urticaria, angioedema, anaphylactic reactions (including anaphylactic shock).
Skin and subcutaneous tissue disorders: rash, urticaria, hyperemia and itching of the skin.
From the reproductive system and mammary gland function: amenorrhea, hyperprolactinemia, galactorrhea, gynecomastia, menstrual disorders. In such cases, the use of the drug should be discontinued.
Laboratory indicators: increased liver enzymes, increased serum creatine phosphokinase.
In adolescents and patients with severe renal impairment (renal failure), which impairs the excretion of metoclopramide, the development of adverse reactions should be monitored particularly closely. If they occur, the use of the drug should be discontinued immediately.
Expiration date
4 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister pack, 5 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.
