Cerucal

Cerucal is a propulsant. Stimulates peristalsis function.

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Indications Cerucal

In adults, it is used to prevent the development of vomiting with nausea after operations, as well as after radiotherapy procedures. In addition, it is used in the symptomatic treatment of nausea with vomiting (this includes cases that occur against the background of acute migraine attacks).

In children, it is used as a second-line agent to prevent vomiting with delayed nausea (caused by chemotherapy procedures), as well as the same symptoms that occur after surgery.

Release form

Released as an injection solution, in 2 ml ampoules. Inside a separate pack there are 10 ampoules with solution.

Pharmacodynamics

Metoclopramide is a central dopamine antagonist that also has peripheral cholinergic activity. Among its main properties are: antiemetic, and in addition, accelerating the process of gastric emptying and the passage of food masses through the small intestine.

The antiemetic properties are due to the action on the center of the brain stem (chemoreceptors are the activating area of the vomiting center). Most likely, this is due to the slowing down of the activity of dopamine neurons.

The process of increasing peristalsis is partially carried out with the participation of higher centers, although a mechanism with peripheral action in combination with the activation of the function of postganglionic cholinergic conductors, as well as, possibly, with the suppression of dopamine receptors inside the small intestine and stomach, may also (also partially) participate in it.

Through the parasympathetic nervous system and hypothalamus, it directs and regulates the motor function of the upper gastrointestinal tract. It increases intestinal and gastric tone, accelerates the process of emptying, affects intestinal peristalsis, prevents esophageal and pyloric reflux, and reduces gastrostasis. It stabilizes the process of bile secretion, eliminates gallbladder dyskinesia, and reduces spasms of the sphincter of Oddi, without changing its tone.

Side effects mainly include extrapyramidal manifestations, which are provoked by the blocking effect of dopamine receptors on the central nervous system.

Long-term use of metoclopramide may provoke an increase in serum prolactin levels due to the lack of dopaminergic inhibition of the process of secretion of this element. In this case, menstrual cycle disorders with galactorrhea were observed in women, and gynecomastia in men. These manifestations passed after discontinuation of the drug.

Pharmacokinetics

The effect on the gastrointestinal tract begins 1-3 minutes after intravenous injection, and also 10-15 minutes after this procedure. The antiemetic effect lasts for 12 hours.

Synthesis of the substance with plasma protein is 13-30%. The distribution volume is 3.5 l/kg. The metabolic process occurs inside the liver. Half-life is 4-6 hours. The substance passes through the placenta and the BBB, and can also penetrate into breast milk.

Approximately 20% of the dose is excreted in its original form, and the remaining approximately 80%, after liver metabolism processes, is excreted through the kidneys, combined with sulfuric or glucuronic acid.

Renal failure in the patient. In severe cases, the CC level decreases to 70%, and the half-life increases (approximately 10 hours with a CC level of 10-50 ml/minute, and 15 hours with a CC level <10 ml/minute).

The patient has liver failure. In liver cirrhosis, accumulation of metoclopramide was observed, against the background of which a decrease in plasma clearance occurred (by 50%).

Dosing and administration

The injection solution is administered intramuscularly or intravenously. For the intravenous procedure, metoclopramide must be administered slowly, by bolus injection (duration – less than 3 minutes).

In adults, to prevent the development of vomiting with nausea after surgery, a single dose of 10 mg is required.

For symptomatic relief of vomiting with nausea (also those that occur due to acute migraine attacks), and at the same time relief of the same symptoms provoked by radiotherapy, a single dose of 10 mg is prescribed (administered no more than 3 times a day).

The daily dosage should not exceed 30 mg (or 0.5 mg/kg).

The drug in injection form should be used for the shortest possible period of time, followed by a rapid transition to rectal or oral forms of metoclopramide.

In children, to prevent nausea and vomiting after surgery, metoclopramide should be administered after the procedure.

Usually the solution is administered in the amount of 0.1-0.15 mg/kg, no more than 3 times a day. In this case, no more than 0.5 mg/kg of the drug can be administered per day. If further use of Cerucal is necessary, it is necessary to observe at least 6-hour intervals between procedures.

Dosage regimen:

• children 1-3 years old (weight 10-14 kg) – dosage 1 mg (maximum three times a day);
• children 3-5 years old (weight 15-19 kg) – dosage 2 mg (no more than 3 times per day);
• children 5-9 years old (weight 20-29 kg) – dosage 2.5 mg (maximum 3 times a day);
• children and adolescents aged 9-18 years (weight 30-60 kg) – dosage 5 mg (maximum three times per day);
• adolescents aged 15-18 years (weight over 60 kg) – dosage 10 mg (no more than 3 times a day).

If postoperative vomiting with nausea is diagnosed, the solution can be used for no longer than 48 hours.

To relieve vomiting along with nausea in a delayed form (due to chemotherapy procedures), metoclopramide can be used for a maximum of 5 days.

In elderly patients, a dose reduction should be considered because of age-related declines in liver and kidney function.

Functional renal disorder.

People with terminal stage pathology (creatinine clearance rate is ≤15 ml/minute) need to reduce the drug dosage by 75%.

For people with severe or moderate forms of the disease (CC is 15-60 ml/minute), the dose is reduced by 50%.

Liver failure.

People with severe functional liver dysfunction require a 50% reduction in the dosage of the solution.

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Use Cerucal during pregnancy

Numerous test results involving pregnant women (more than 1000 using drugs) showed that there is no toxic effect, resulting in fetotoxicity or malformations.

Metoclopramide may be prescribed to pregnant women if there are clinical indications. The medicinal properties of the substance (like other neuroleptics), provided that Cerucal is used in the later stages, can provoke the development of extrapyramidal disorder in the child. As a result, it is recommended to refuse to use the drug during this period. The condition of the newborn should also be monitored if the drug is used.

Contraindications

Contraindications are:

• the patient has an intolerance to metoclopramide or other components of the drug;
• bleeding in the gastrointestinal tract;
• mechanical intestinal obstruction;
• perforation inside the gastrointestinal tract;
• diagnosed pheochromocytoma or suspected of it (since there is a risk of increased blood pressure in a severe form);
• history of late-stage dyskinesia induced by metoclopramide or other neuroleptics;
• epilepsy (increased intensity and frequency of seizures);
• shaking palsy;
• combined use with levodopa or dopamine agonists;
• diagnosed methemoglobinemia due to the use of metoclopramide or a history of NADH-cytochrome b5 reductase deficiency;
• prolactin-dependent tumors;
• increased convulsive readiness (extrapyramidal motor disorders);
• Since there is a risk of developing extrapyramidal syndrome, it should not be prescribed to infants under 1 year of age.

Since the solution of the medicine contains sodium sulfite, it is prohibited to prescribe it to people with bronchial asthma and sulfite intolerance.

Side effects Cerucal

The introduction of the solution may provoke certain side effects:

• immune manifestations: hypersensitivity and anaphylactic symptoms (this includes anaphylaxis, especially with intravenous injection);
• lymphatic reactions and manifestations of the hematopoietic system: development of methemoglobinemia, which may occur due to a deficiency of NADH-cytochrome-b5-reductase (especially in young children), and also sulfhemoglobinemia, which develops mainly due to the combined use of sulfur-releasing drugs (in high doses);
• manifestations from the cardiovascular system: development of bradycardia (especially as a result of intravenous injection). Due to bradycardia, short-term cardiac arrest is possible after administration of the drug. AV block, sinus node arrest (often due to intravenous injections), prolongation of the QT interval and a decrease in blood pressure indicators also occur. In addition, ventricular tachycardia occurs, shock is observed, blood pressure levels increase in an acute form (in people with pheochromocytoma), as well as fainting in the case of intravenous injection;
• reactions of the endocrine system: the appearance of gynecomastia, galactorrhea and amenorrhea, as well as hyperprolactinemia and menstrual cycle disorders;
• gastrointestinal disorders: dry mouth, constipation, nausea and diarrhea;
• NS reactions: a malignant form of neuroleptic syndrome (characterized by the following symptoms: seizures, fever, changes in blood pressure, muscle rigidity, and loss of consciousness), which usually develops in epileptics. In addition, there is also a feeling of drowsiness, headaches, and depression of the level of consciousness;
• skin disorders: urticaria, skin itching, rashes, as well as Quincke's edema and hyperemia;
• mental disorders: the appearance of hallucinations, a feeling of restlessness and anxiety, a state of depression and confusion;
• laboratory test results: increased levels of liver enzymes;
• systemic manifestations: increased fatigue and development of asthenia.

Extrapyramidal disorders resulting from the administration of a single dose (mainly in adolescents and children) or as a result of exceeding the required dose:

• dyskinetic syndrome (the appearance of reflex spasmodic movements (neck, head and shoulders), tonic blepharospasm, spasm in the area of the masticatory and facial muscles, as well as the lingual and pharyngeal muscles, lingual deviations, spinal strain caused by spasms of flexion of the arms and extension of the legs, as well as incorrect positioning of the neck with the head);
• shaking palsy (development of rigidity, tremor, and along with this, akinesia);
• acute form of dystonia;
• late stage dyskinesia (may develop into permanent dyskinesia during or after long-term treatment (often in older people));
• akathisia.

Overdose

Signs of overdose include: feeling of drowsiness, irritability, confusion, feeling of anxiety with its increase, as well as suppression of the level of consciousness and occurrence of convulsions. Extrapyramidal disorders and disorders in the work of the cardiovascular system with the development of bradycardia and increase/decrease in blood pressure may develop. Hallucinations, cardiac arrest and respiratory function, as well as manifestations of dystonia are possible.

If extrapyramidal disorders occur (due to or without overdose), symptomatic therapy should be performed (children are prescribed benzodiazepines, and adults are prescribed anticholinergic drugs of the antiparkinsonian type).

Given the patient's condition, it is necessary to eliminate emerging disorders and regularly monitor the functioning of the respiratory system and cardiovascular system.

Interactions with other drugs

It is prohibited to combine dopamine agonists and levodopa with Cerucal, since in this case mutual antagonism occurs.

You should not drink alcohol while using metoclopramide, as alcohol increases its sedative properties.

Due to the combination with oral drugs (such as paracetamol), changes in their absorption are possible, since metoclopramide affects gastric motility.

Anticholinergic drugs, as well as morphine derivatives, when combined with Cerucal, cause mutual antagonism regarding the effect on the motility of the digestive tract.

Medicines that slow down the work of the central nervous system (neuroleptics, morphine derivatives, barbiturates with H1 receptor blockers, antihistamines (sedative type), as well as sedative antidepressants and clonidine with related drugs) enhance the properties of metoclopramide.

Neuroleptics in combination with metoclopramide can provoke the development of cumulative effects, as well as extrapyramidal disorders.

Serotonergic drugs (for example, SSRIs) in combination with Cerucal can increase the likelihood of serotonin intoxication.

Combination with digoxin may reduce its bioavailability. It is necessary to carefully monitor plasma digoxin levels during treatment.

Concomitant use with cyclosporine increases its bioavailability (peak level by 46% and effect by 22%). It is necessary to closely monitor the plasma level of cyclosporine. So far, it has not been possible to definitively identify the medicinal consequences of this phenomenon.

Use of the drug with mivacurium or suxamethonium may increase the duration of neuromuscular blockade (plasma cholinesterase is suppressed).

Strong inhibitors of the CYP2D6 element. The AUC of metoclopramide increases with such a combination (combination with paroxetine or fluoxetine). Although there is no precise data on the medicinal significance of this phenomenon, it is necessary to monitor the condition of patients for the occurrence of side effects.

Cerucal is able to increase the duration of action of succinylcholine.

Since the medicinal solution contains sodium sulfite, thiamine taken with the medicine can be quickly broken down inside the body.

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Storage conditions

Cerucal must be stored away from sunlight and out of the reach of small children. Do not freeze the solution. Temperature values are maximum 30°C.

Shelf life

Cerucal can be used for a period of 5 years from the date of release of the medicinal solution.