Cerucal

Cerukal is a propulsant. Stimulates the function of peristalsis.

[1], [2], [3]

Indications of the cerukala

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

In children, it is used as a means of the second line - preventing vomiting with nausea of delayed type (caused by chemotherapy procedures), and besides the same symptoms that arise after surgical operations.

Release form

Release in the form of an injection solution, in ampoules of 2 ml. Inside a separate pack - 10 ampoules with a solution.

Pharmacodynamics

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

Antiemetic properties arise as a result of exposure to the center of the brain stem (chemoreceptors are the activating region of the vomiting center). Most likely, this is due to the slowing down of dopamine neuronal activity.

The process of enhancing peristalsis is partially realized with the participation of higher centers, although a mechanism with peripheral action combined with activation of the function of postganglionic cholinergic conductors and, possibly, suppression of dopamine receptors inside the small intestine and stomach can also participate in it (also partially).

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

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

Prolonged use of metoclopramide may trigger an increase in serum prolactin levels due to a lack of dopaminergic slowing of the process of isolation of this element. At the same time, women had disorders of the menstrual cycle with galactorrhea, and in men - gynecomastia. These manifestations occurred after the drug was withdrawn.

Pharmacokinetics

Exposure to the gastrointestinal tract begins 1-3 minutes after IV injection, and also 10-15 minutes after this procedure. Antiemetic effect lasts for 12 hours.

Synthesis of substance with plasma protein - 13-30%. The distribution volume is 3.5 l / kg. The metabolic process is carried out inside the liver. The half-life is 4-6 hours. The substance passes through the placenta and BBB, and in addition can penetrate into the mother's milk.

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

Kidney failure in the patient. With a severe degree of pathology, the level of QC is reduced to 70%, and the half-life increases (approximately 10 hours at a CC of 10-50 ml / minute, and 15 hours at a CC <10 ml / minute).

Lack of the patient's liver. In hepatic cirrhosis metoclopramide was cumulated, against which a decrease in plasma clearance (by 50%) occurred.

Dosing and administration

Injection solution is administered in / m or IV manner. With / in the procedure, metoclopramide is required to be administered slowly, by bolus injection (duration - less than 3 minutes).

In adults, in order to prevent the development of vomiting with nausea after surgery, a single dosage of drugs in the amount of 10 mg is necessary.

With symptomatic elimination of vomiting with nausea (also those that arise due to acute migraine attacks), and at the same time elimination of the same symptoms provoked by radiotherapy, a single dose of 10 mg is given (inject no more than 3 times for day).

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

Use the drug in the form of an injection should be during the shortest possible period of time, with a rapid subsequent transition to rectal or oral forms of metoclopramide.

Children, when preventing nausea with vomiting after surgery, should be administered metoclopramide at the end of 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 Cerucalum is required, a minimum of 6-hour intervals between procedures should be observed.

Dosing regimen:

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

With diagnosed postoperative vomiting with nausea, you can apply the solution no longer than 48 hours.

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

Older people need to consider the option of lowering the dose, because of the age they have a decrease in hepatic and renal function.

Functional renal impairment.

People with a terminal pathology stage (level of the creatinine cleansing factor is ≤15 ml / minute) need to reduce the dosage of drugs by 75%.

People with a severe or moderate form of the disease (QC value is 15-60 ml / minute) dose size is reduced by 50%.

Insufficiency of the liver.

People with functional hepatic impairment in severe form need to reduce the dosage of the solution by 50%.

[4]

Use of the cerukala during pregnancy

A variety of test results with the participation of pregnant women (more than 1000 using drugs) have shown that there is no toxic effect, resulting in fetotoxicity or malformation.

Metoclopramide is allowed to be given to pregnant women in the presence of clinical indications. The medicinal properties of the substance (like other neuroleptics), provided that Cerukal is used in later periods, can provoke the development of extrapyramidal disorder in the child. Therefore, it is recommended to stop using drugs during this period. Also, the condition of the newborn should be monitored in the case of a drug.

Contraindications

Contraindications are:

• the patient has intolerance to metoclopramide or other elements of the drug;
• bleeding in the gastrointestinal tract;
• intestinal obstruction of mechanical type;
• perforation inside the gastrointestinal tract;
• diagnosed pheochromocytoma or suspected of it (since there is a risk of increasing blood pressure in severe form);
• present in the anamnesis late stage of dyskinesia, provoked metoclopramide or other neuroleptics;
• epilepsy (increased intensity and frequency of seizures);
• tremor paralysis;
• combined use with levodopa or dopamine agonists;
• diagnosed methemoglobinemia due to the use of metoclopramide or a history of a deficiency of NADH-cytochrome-b5-reductase;
• depending on the prolactin level of the tumor;
• increased convulsive readiness (motor extrapyramidal disorders);
• since there is a possibility of developing an extrapyramidal syndrome, it can not be administered to infants until the first year.

Since sodium sulfite is contained in the drug solution, it is forbidden to prescribe it to people with bronchial asthma and intolerance to sulfite.

Side effects of the cerukala

The introduction of the solution can provoke some side effects:

• immune manifestations: hypersensitivity and anaphylactic symptoms (this includes anaphylaxis, especially with IV injection);
• lymphatic reactions and manifestations of the hematopoietic system: the development of methemoglobinemia, possibly due to a lack of NADH-cytochrome b5-reductase (especially in young children), and in addition to sulfemoglobinemia, which develops mainly due to the combined use of sulfur-releasing drugs (in high doses);
• manifestations on the part of the CAS: the development of bradycardia (especially as a result of intravenous injection). Because of bradycardia, a short-term cardiac arrest after drug administration is possible. Also occurs AV blockade, stopping the sinus node (often due to intravenous injection), lengthening the interval-QT and lowering blood pressure. In addition, there is a ventricular tachycardia, a shock condition is observed, an increase in blood pressure in acute form (in people with pheochromocytoma), and fainting in the case of IV injection;
• reactions of the endocrine system: the appearance of gynecomastia, galactorrhea and amenorrhea, and in addition hyperprolactinaemia and menstrual cycle disorders;
• disorders in the work of the digestive tract: dry mouth mucous membranes, constipation, nausea and diarrhea;
• reactions of the NS: malignant form of neuroleptic syndrome (it is characterized by such signs: the appearance of seizures, heat, 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 edema of Quincke and hyperemia;
• mental disorders: the appearance of hallucinations, anxiety and anxiety, a state of depression and confusion;
• indicators of laboratory tests: an increase in the level of hepatic enzymes;
• systemic manifestations: increased fatigue and development of asthenia.

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

• dyskinetic syndrome (the appearance of reflex spasmodic movements (neck, head and shoulders), tonic type blepharospasm, spasm in the masticatory and facial musculature, and lingual and pharyngeal muscles, linguistic abnormalities, vertebral overstrain caused by spasms of flexing of the arms and extension of the legs, and wrong position of neck with head);
• tremor paralysis (development of rigidity, tremor, and with it akinesia);
• acute form of dystonia;
• late stage of dyskinesia (can develop into a permanent for a period of prolonged treatment or after it (often in the elderly));
• akathisia.

Overdose

Among the signs of overdose: a feeling of drowsiness, irritability, confusion, a sense of anxiety with its intensification, and in addition suppression of the level of consciousness and the occurrence of seizures. Extrapyramidal disorders and disorders in the work of SSS may develop with the development of bradycardia and an increase / decrease in blood pressure. Possible the appearance of hallucinations, cardiac arrest and respiratory function, and in addition to this manifestation of dystonia.

When extrapyramidal disorders occur (due to exceeding the dose or without it), symptomatic therapy should be performed (children are prescribed benzodiazepines, and adults with holinolitic drugs of the antiparkinsonian type).

Taking into account the patient's condition, it is necessary to eliminate the arising disorders and regularly monitor the work of the respiratory system and CCC.

Interactions with other drugs

It is forbidden to combine with Zerukalom agonists dopamine and levodopa, since in this case there is mutual antagonism.

Do not drink alcohol when using metoclopramide, since alcohol enhances its soothing properties.

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

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

Drugs that slow down the CNS (neuroleptics, morphine derivatives, barbiturates with anti-histamine H1 receptor blockers (sedative type), and 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 Zerukal can increase the likelihood of the appearance of serotonin intoxication.

Combination with digoxin can reduce its bioavailability. It is required to carefully monitor the plasma level of digoxin during the treatment period.

Simultaneous use with cyclosporin increases its bioavailability (peak level by 46% and effect by 22%). It is necessary to closely monitor the plasma index of cyclosporine. While it was not possible to finally identify the medicinal consequences of this phenomenon.

The use of a drug with mivakurium or suxamethonium may increase the duration of neuromuscular blocking (plasma cholinesterase is suppressed).

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

Tserukal is able to increase the duration of exposure to succinylcholine.

Since the drug solution contains sodium sulfite, the thiamine taken with the drug can be quickly cleaved within the body.

[5], [6]

Storage conditions

Cerucal is required to be stored, protecting from sunlight, inaccessible to young children. Do not freeze the solution. Temperature values are a maximum of 30 ° C.

Shelf life

Cerucal can be used in the period of 5 years since the release of the drug solution.