Cerucal, tablets 10 mg 50 pcs

Pharmacotherapeutic group: A central dopamine receptor blocker.

ATX code: A03FA01

Pharmacological properties

Pharmacodynamics

p> Antiemetic, is a specific blocker of dopamine (D2) and serotonin receptors. The mechanism of action is based on both the central and peripheral effects of metoclopramide. The antiemetic effect is associated with blockade of dopamine receptors in the brain, which causes an increase in the threshold of irritation of the vomiting center. It has antiemetic effect, eliminates nausea and hiccups. It reduces esophageal motility, increases the tone of the lower esophageal sphincter, accelerates gastric emptying, and also accelerates the movement of food through the small intestine without causing diarrhea. Normalizes bile secretion, reduces spasm of Oddi sphincter, does not change its status, eliminates gall bladder dyskinesia. Stimulates the secretion of prolactin.

Pharmacokinetics

After oral administration is rapidly absorbed, time to reach maximum plasma concentration 30-120 minutes. Bioavailability is 60-80%.

It is metabolized in the liver. Elimination half-life is 3 to 5 hours; in renal function disorders it may be increased up to 14 hours. It is excreted by kidneys during the first 24 hours unchanged and as metabolites (about 80% of the dose taken). It easily passes through the blood-brain barrier and is excreted with breast milk.

Indications

Vomiting, Hiccups, Reflux esophagitis, Gastric and 12 duodenal ulcer, Biliary dyskinesia, Meteorism, Nausea, Gastroduodenitis

• 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.
  

Active ingredient

Metoclopramide

Composition

1 tablet contains: the active substance metoclopramide hydrochloride monohydrate 10.54 mg (in terms of metoclopramide hydrochloride 10.00 mg); excipients: potato starch 36.75 mg, lactose monohydrate 76.65 mg, gelatin 2.16 mg, colloidal silicon dioxide 2.60 mg, magnesium stearate 1.30 mg, purified water q.s.

How to take, the dosage

Intravenously.

Adults and children over 15 years of agewith a body weight greater than 60 kg

The recommended dose is 1 tablet (10 mg) up to three times daily.

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

Children over 15 years of age with a body weight less than 60 kg

The recommended dose is 1/2 tablet (5 mg) 1-3 times daily.

The maximum recommended daily dose is 0.5 mg/kg/day.

In order to avoid overdose, a minimum interval of 6 hours between doses should be observed, even in case of vomiting.

The maximum duration of treatment is 5 days.

Elderly patients

In elderly patients, dose reduction may be required depending on renal and hepatic function and general condition.

Renal failure

In patients with end-stage renal failure (creatinine clearance less than 15 mL/min), the daily dose should be reduced by 75%.

In patients with moderate to severe renal failure (CKR 15-60 ml/min), the dose should be reduced by 50%.

Hepatic impairment

In patients with severe hepatic impairment, the dose should be reduced by 50%.

Interaction

The concomitant use of metoclopramide with levodopa or dopamine receptor agonists is contraindicated due to mutual antagonism.

Alcohol increases the sedative effect of metoclopramide.

Combinations requiring caution

Due to the prokinetic effect of metoclopramide, absorption of some drugs may be impaired.

M-cholinoblockers and morphine derivatives are mutually antagonistic to metoclopramide with respect to effects on gastrointestinal peristalsis.

The CNS depressant drugs (morphine derivatives, tranquilizers, H1-histamine receptor blockers, antidepressants with sedative effect, barbiturates, clonidine and other drugs of these groups) may increase the sedative effect under the influence of metoclopramide.

Metoclopramide increases the effect of neuroleptics with respect to extrapyramidal symptoms.

In concomitant use of oral metoclopramide and tetrabenazine there is a potential for dopamine deficiency, which may be accompanied by increased muscle rigidity or spasm, difficulty speaking or swallowing, restlessness, tremor, involuntary muscle movements, including facial muscles.

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

Methoclopramide reduces the bioavailability of digoxin. Plasma concentrations of digoxin should be monitored.

Methoclopramide increases the bioavailability of cyclosporine (C_max by 46% and exposure by 22%). Plasma concentrations of cyclosporine should be monitored carefully. The clinical consequences of this interaction have not been established.

Exposure of metoclopramide is increased when used concomitantly with potent CYP2D6 isoenzyme inhibitors such as fluoxetine and paroxetine. Although the clinical significance of such interaction has not been established, it is necessary to monitor the occurrence of adverse reactions in patients.

The concomitant use of metoclopramide with atovachone significantly decreases the plasma concentration of atovachone (about 50%). Concomitant use of metoclopramide with atovachone is not recommended.

The concomitant use of metoclopramide with bromocriptine increases the plasma concentration of bromocriptine.

Metoclopramide increases absorption of tetracycline from the small intestine.

Metoclopramide enhances absorption of mexiletine and lithium.

Metoclopramide reduces absorption of cimetidine.

Special Instructions

Caution should be exercised when using Cerucal^® in elderly patients.

Nervous system disorders may occur, especially in children and young patients and/or when using high doses, usually at the beginning of treatment or after a single use. The use of Cerucal^® should be stopped immediately in case of extrapyramidal symptoms. Reactions are completely reversible after discontinuation of treatment, but may require symptomatic therapy (benzodiazepines in children and/or anticholinergic antiparkinsonian drugs in adults).

In order to avoid an overdose of Cercucal^® , a minimum interval of 6 hours between doses should be observed, even in case of vomiting.

Long-term treatment with the drug Cerucal^® may lead to the development of tardive dyskinesia, potentially irreversible, especially in elderly patients. The duration of treatment should not exceed 3 months due to the risk of tardive dyskinesia. If there are signs of tardive dyskinesia, treatment should be discontinued.

When using metoclopramide simultaneously with neuroleptics, as well as during monotherapy with metoclopramide a neuroleptic malignant syndrome has been observed. Treatment with Cerucal^® must be stopped immediately if symptoms of neuroleptic malignant syndrome appear and an appropriate therapy should be used.

Cautious use in patients with concomitant neurological diseases and in patients taking drugs acting on the central nervous system is necessary.

When using Zerucal^® the symptoms of Parkinson’s disease may also be noted.

There have been reported cases of methemoglobinemia that may be caused by a deficiency of NADN-dependent cytochrome-b5 reductase enzyme. In this case, Zerucal^® should be immediately and completely discontinued and appropriate measures taken.

Severe cardiovascular side effects including vascular failure, marked bradycardia, cardiac arrest and QT interval prolongation have been reported.

Cautions are necessary when using Cercucal^®, in elderly patients, patients with cardiac abnormalities (including prolongation of the QT interval), patients with electrolyte and water balance disorders, bradycardia, and patients taking other QT interval prolonging medications.

In moderate to severe renal impairment and severe hepatic impairment, dosage reduction is recommended (see section “Dosage and administration”).

Influence on driving and operating machinery

Caution should be taken when operating vehicles and other machinery as the drug may cause drowsiness and dyskinesia.

Synopsis

White, round, flat tablets with beveled intact edges, smooth homogeneous surface, with a groove on one side.

Contraindications

• High sensitivity to metoclopramide and drug components;
• gastrointestinal bleeding, mechanical intestinal obstruction or perforation of the gastrointestinal wall, conditions in which stimulation of gastrointestinal peristalsis is a risk;
• confirmed or suspected pheochromocytoma due to risk of severe arterial hypertension;
• late dyskinesia that developed after a history of treatment with neuroleptics or metoclopramide;epilepsy (increased frequency and severity of seizures);
• Parkinson’s disease;
• simultaneous use with levodopa and dopamine receptor agonists;
• methemoglobinemia due to metoclopramide or a history of cytochrome-b5 nicotinamide adenine dinucleotide (NADN) deficiency;
• prolactinoma or prolactin-dependent tumor;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• children under 15 years of age;
• breastfeeding period.

Cautions

When used in elderly patients; In patients with impaired cardiac conduction (including QT interval prolongation), impaired water-electrolyte balance, bradycardia, taking other QT interval prolonging drugs, arterial hypertension; In patients with concomitant neurologic diseases, depression (history); in moderate to severe renal failure (CKD 15-60 ml/min); in severe hepatic failure; in pregnancy.

Side effects

The incidence of adverse reactions is classified as follows: very common (≥ 1/10), common (≥ 1/100 – < 1/10), infrequent (≥ 1/1000 – < 1/100), rare (≥ 1/10000 – < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated based on available data).

Disorders of the blood and lymphatic system: frequency unknown – methemoglobinemia, probably associated with enzyme deficiency of NADH-dependent cytochrome-b5 reductase, especially in neonates, sulfhemoglobinemia (most often with concomitant use of high doses of sulfur-containing drugs), leukopenia, neutropenia, agranulocytosis.

Disorders of the immune system: infrequent – hypersensitivity; frequency unknown – anaphylactic reactions (including anaphylactic shock), allergic reactions (urticaria, maculopapular rash).

Endocrine system disorders*: infrequent – amenorrhea, hyperprolactinemia; rarely – galactorrhea; frequency unknown – gynecomastia.

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

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

Nervous system disorders: very common – somnolence; common – asthenia, extrapyramidal disorders (especially in children and young patients and/or when exceeding the recommended doses of the drug, even after a single administration), parkinsonism, akathisia; infrequent – dystonia (including visual disturbance and involuntary eye movement – oculogeric crisis), dyskinesia, impaired consciousness; infrequent – seizures, especially in patients with epilepsy; frequency unknown – tardive dyskinesia, sometimes persistent, during or after long-term treatment, especially in elderly patients, neuroleptic malignant syndrome.

Cardiac disorders: frequent – bradycardia; frequency unknown – cardiac arrest, which may be caused by bradycardia, atrioventricular block, sinus node block, QT interval prolongation on electrocardiogram, “pirouette” type arrhythmia.

Vascular disorders: frequent – decrease of blood pressure; frequency unknown – cardiogenic shock, acute increase of blood pressure in patients with pheochromocytoma, transient increase of blood pressure.

Gastrointestinal disorders: frequently – nausea, diarrhea, constipation.

Recreational and urinary tract disorders:frequency unknown – polyuria, urinary incontinence.

Renital and mammary gland disorders: unknown frequency – sexual dysfunction, priapism.

Indesirable reactions most common with high doses of the drug

– Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian syndrome, akathisia have developed even after using a single dose of the drug, especially in children and young patients (see See section “Special Precautions”).

Drowsiness, decreased level of consciousness, confusion, hallucinations.

Overdose

Symptoms

Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucinations, irritability, dizziness, bradycardia, changes in blood pressure, cardiac and respiratory arrest, abdominal pain.

Treatment

If extrapyramidal symptoms develop due to overdose or other cause, treatment is symptomatic only (benzodiazepines in children and/or anticholinergic antiparkinsonian drugs in adults).

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

There is no specific antidote.

Pregnancy use

Pregnancy

The numerous data obtained on use in pregnant women (more than 1000 described cases) indicate the absence of fetotoxicity and the ability to cause malformations in the fetus. Metoclopramide may be used during pregnancy (I-II trimesters) only if the potential benefit to the mother exceeds the potential risk to the fetus. Due to the pharmacological characteristics (similar to other neuroleptics), when using metoclopramide in late pregnancy, the possibility of extrapyramidal symptoms in the newborn cannot be excluded. Metoclopramide should not be used at the end of pregnancy (during the third trimester). When using metoclopramide, the condition of the newborn should be monitored.

Period of breastfeeding

Methoclopramide is excreted in small amounts with the breast milk. The possibility of adverse reactions in the child cannot be excluded. The use of metoclopramide during breastfeeding is not recommended. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Similarities

Cerucal, Metoclopramide