Instructions for use Cerucal tablets 10 mg bottle No. 50
Composition
active ingredient: metoclopramide hydrochloride;
1 tablet contains metoclopramide hydrochloride (as metoclopramide hydrochloride monohydrate) 10 mg;
Excipients: potato starch, lactose monohydrate, gelatin, precipitated silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white, round, flat tablets with a bevel, a break line on one side, undamaged edges and uniform appearance.
Pharmacotherapeutic group
Peristaltic stimulants (propulsants). Metoclopramide. ATX code A03F A01.
Pharmacological properties
Pharmacodynamics
Metoclopramide is a central dopamine antagonist that also exhibits peripheral cholinergic activity.
Two main effects are noted: an antiemetic effect and an effect of accelerating gastric emptying and passage through the small intestine.
The antiemetic effect is the result of 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 partially 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 of the stomach and small intestine. Through the hypothalamus and parasympathetic nervous system, it regulates and coordinates the motor activity of the upper gastrointestinal tract. Increases the tone of the stomach and intestines, accelerates gastric emptying, reduces gastrostasis, prevents pyloric and esophageal reflux, stimulates intestinal peristalsis. Normalizes bile secretion, reduces spasm of the sphincter of Oddi, does not change its tone, eliminates gallbladder dyskinesia.
Undesirable effects are manifested mainly by 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, but these symptoms resolved after discontinuation of treatment.
Pharmacokinetics
After oral administration, it is rapidly and completely absorbed. 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 after 20-40 minutes after oral administration. The bioavailability of oral metoclopramide is on average 60-80%. The antiemetic effect persists for 12 hours. The half-life is from 2.6 to 4.6 hours. Only a small part of the dose of metoclopramide taken binds to blood plasma proteins. The volume of distribution ranges from 2.2 to 3.4 l/kg. Metabolized in the liver. Penetrates the blood-brain and placental barriers, penetrates into breast milk. 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.
Kidney failure.
In patients with severe renal insufficiency, the clearance of metoclopramide is reduced by up to 70% and the plasma half-life is increased (about 10 hours for creatinine clearance 10-50 ml/min and 15 hours for creatinine clearance <10 ml/min).
Liver failure.
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 those 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;
concomitant use with levodopa or dopaminergic agonists (see section "Interaction with other medicinal products and other types of interactions");
established methemoglobinemia with metoclopramide use or history of NADH-cytochrome-b5-reductase deficiency; prolactin-dependent tumors; increased seizure readiness (extrapyramidal movement disorders);
children under 1 year of age, due to the increased risk of extrapyramidal disorders (see section "Special instructions for use").
Interaction with other medicinal products and other types of interactions
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.
The prokinetic action of metoclopramide may affect the absorption of some drugs.
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, anxiolytics, sedative antihistamines - H1 receptor blockers, sedative antidepressants, barbiturates, clonidine and related drugs): Central nervous system inhibitors potentiate the sedative effect of metoclopramide.
Neuroleptics: when metoclopramide is used in combination with other neuroleptics, a cumulative effect and extrapyramidal disorders are possible.
Serotonergic drugs: Taking metoclopramide in combination with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), may increase the risk of developing 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 blockade (due to inhibition of plasma cholinesterase). Metoclopramide may prolong the action of succinylcholine.
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 increase is unknown, patients should be monitored for adverse reactions.
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 (including 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 when high doses are used. 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 doses 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 (see section 4.8). Treatment should be discontinued if clinical signs of tardive dyskinesia appear.
When metoclopramide is used in combination with neuroleptics, as well as with metoclopramide monotherapy, the development of neuroleptic malignant syndrome has been reported (see section "Adverse reactions"). 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 in patients receiving treatment with other drugs acting on the central nervous system (see section "Contraindications").
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. administration of methylene blue).
Heart disorders.
Metoclopramide should be used with caution, especially when administered intravenously, in elderly patients, patients with cardiac conduction disorders (including QT prolongation), patients with electrolyte imbalance, bradycardia, and patients taking drugs that prolong the QT interval.
Impaired kidney and liver function.
A dose reduction is recommended for patients with renal impairment or severe hepatic impairment (see section 4.2).
If the patient has been diagnosed with intolerance to some sugars, he should consult his doctor before taking this medicine. The drug contains lactose, therefore patients suffering from rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not be prescribed Cerucal.
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 on pregnant women (more than 1000 outcomes with the drug) indicate the absence of any malformative toxicity or fetotoxicity. Metoclopramide can be used during pregnancy if clinically needed. Due to its pharmacological properties (as with other neuroleptics), the possibility 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.
Breast-feeding.
Metoclopramide is excreted in small amounts in breast milk. It is not excluded that metoclopramide may affect the breastfed infant. 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 adverse reactions from the nervous system and other side effects, 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 |
| 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 for 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 the increased risk of extrapyramidal disorders. Tablets should not be used to treat children weighing less than 30 kg. For children weighing <30 kg, metoclopramide should be used in dosage forms that allow for appropriate dosing.
Overdose
Symptoms: drowsiness, depressed level of consciousness, confusion, irritability, anxiety and its increase, convulsions, extrapyramidal disorders, dysfunction of the cardiovascular system with bradycardia and increased or decreased blood pressure, hallucinations, respiratory and cardiac arrest.
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.
Adverse reactions
Cardiovascular system: bradycardia, especially with intravenous administration, cardiac arrest for a short time after injection, which may be a consequence of bradycardia (see section "Special instructions for use"), atrioventricular block, sinus node arrest, especially with intravenous administration, QT prolongation, torsades de pointes, arterial hypotension, especially with intravenous administration, shock, syncope with parenteral administration, acute arterial hypertension in patients with pheochromocytoma (see section "Contraindications"), temporary increase in blood pressure.
From the endocrine system *: amenorrhea, hyperprolactinemia, galactorrhea, gynecomastia, menstrual disorders.
Gastrointestinal: nausea, dry mouth, constipation, diarrhea.
Immune system disorders: hypersensitivity, anaphylactic reactions (including anaphylactic shock) mainly with intravenous administration.
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, tongue deviation, spasm of the pharyngeal and tongue muscles, incorrect head and neck posture, overstrain of the spine, spasmodic flexion of the arms, spasmodic extension of the legs), headache, dizziness, drowsiness, extrapyramidal disorders (which may occur even after a single dose, mainly in children and adolescents, and/or when the recommended dose is exceeded) (see section "Special precautions for use"), parkinsonism (tremor, muscle rigidity, akinesia), akathisia, dystonia (including visual disturbances and oculogyric crisis), dyskinesia, depressed level of consciousness, tardive dyskinesia (which may be permanent during or after long-term treatment, especially in patients elderly), neuroleptic malignant syndrome (characteristic symptoms: fever, muscle rigidity, loss of consciousness, fluctuations in blood pressure, seizures (mainly in patients with epilepsy)).
Skin: rash, urticaria, hyperemia and itching of the skin, angioedema.
Mental disorders: depression, hallucinations, confusion, anxiety, restlessness.
Laboratory tests: increased liver enzymes.
General disorders: asthenia, fatigue.
* Endocrine disorders during long-term treatment are associated with hyperprolactinemia (amenorrhea, galactorrhea, gynecomastia). In such cases, the drug should be discontinued.
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 drug should be discontinued immediately.
Severe cardiovascular reactions have been reported following intravenous administration of metoclopramide (arrhythmias, e.g. supraventricular extrasystoles, ventricular extrasystoles, tachycardia, ranging from bradycardia to cardiac arrest).
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 and adolescents; drowsiness, depressed level of consciousness, confusion, hallucinations.
Expiration date
5 years.
It is forbidden to use the drug after the expiration date.
Storage conditions
Store in the original packaging to protect from light at a temperature not exceeding 25 °C, out of the reach of children.
Packaging
50 tablets per bottle, 1 bottle per box.
Vacation category
According to the recipe.
Producer
PLIVA Hrvatska d.o.o.
Location of the manufacturer and its business address
Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
