Emeton 4 ml No.5

EMETON 4 ml No.5

Solution for injection 2 mg/ml 4 ml in ampoules No.5

Antiemetic product of central effect, selective antagonist of serotonin receptors 5HT3.

Marketing Authorization No. UA/13447/01/01

Composition

Active ingredient: ondansetron;

1 ml of the solution contains 2 mg of ondansetron (in the form of dihydrate hydrochloride);

Excipients: citric acid monohydrate, sodium citrate, sodium chloride, water for injections.

 

Pharmaceutical form

Solution for injection.

Pharmacotherapeutic group

Anti-vomitting products and medicines that prevent nausea. Serotonin receptor antagonists. (5НТ3). ATC code А04А А01.

Clinical performance

Indications.

Nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy. Prevention and treatment of postoperative nausea and vomiting.

Contraindications

Ondansetron usage with apomorphine hydrochloride is contraindicated, since during their combined use cases of severe arterial hypotension and loss of consciousness have been observed.

Hypersensitivity to any medicine component.

Posology and method of administration

Nausea and vomiting caused by chemotherapy and radiotherapy

The emetic potential of cancer therapy varies according to the dose and combination of chemotherapy and radiotherapy regimens. The choice of dosage regimen depends on the severity of the emetogenic effect.

Adults

Emetogenic chemotherapy and radiotherapy

The recommended intravenous or intramuscular dose of Emeton is 8 mg in the form of a slow injection for at least 30 seconds, shortly before treatment.

For prophylaxis of delayed or prolonged vomiting after the first 24 hours oral or rectal use of the medicine is recommended.

High-grade chemotherapy (e.g. high doses of cisplatinum)

Emeton can be administered as a single dose of 8 mg intravenously or intramuscularly shortly before chemotherapy. Doses above 8 mg (up to 16 mg) can only be used as an intravenous infusion of 50-100 ml of 0.9% sodium chloride solution or other appropriate solvent (see below for "Instructions for use"); infusion should last at least 15 minutes. A single dose of greater than 16 mg can not be used (see section " Administration details").

For high-energy chemotherapy, 8 mg of Emeton or a lower dose should not be diluted and can be administered by slow intravenous or intramuscular injection (at least 30 seconds) immediately prior to chemotherapy followed by a double intravenous or intramuscular administration of 8 mg in 2 and 4 hours or continuous infusion of 1 mg / hour for 24 hours.

The efficacy of Emeton in high-techogenic chemotherapy may be increased by an additional single-dose intravenous administration of dexamethasone sodium phosphate at a dose of 20 mg prior to chemotherapy.

To prevent the delayed or prolonged vomiting after the first 24 hours, oral or rectal use of the medicine is recommended.

Children and adolescents (aged from 6 months to 17 years)

In pediatric practice Emeton should be administered by intravenous infusion in  25-50 ml solution of 0.9% solution of sodium chloride or another appropriate solvent (see below  "Instructions for use") for at least 15 minutes. The dose of the medicine can be calculated by the area of ​​the body surface or the child’s body weight.

Dose calculation according to the area of ​​the child's body surface

Emeton should be administered immediately before chemotherapy with a single intravenous injection at a dose of 5 mg / m², and the intravenous dose should not exceed 8 mg. After 12 hours,  the oral application can be started, which can take another 5 days. Do not exceed the adult dose.

Dose calculation according to the child's body weight  

Emeton should be administered immediately prior to chemotherapy by single intravenous injection at a dose of 0.15 mg / kg. The intravenous dose should not exceed 8 mg. On the first day, you can inject 2 additional intravenous doses at 4-hours intervals. After 12 hours,  the oral application can be started, which can take another 5 days. Do not exceed the adult dose.

Elderly  patients

For patients of over 65 years old,  all intravenous doses should be dissolved and administered within 15 minutes, with repeated application, the interval between injections should be at least 4 hours.

In patients aged 65 to 74, the initial dose of ondansetron is 8 mg or 16 mg, it is administered by intravenous infusion for 15 minutes, which can be continued by administering 2 doses of 8 mg for 15 minutes at intervals between infusions for at least 4 hours.

In patients older than 75 years, the initial intravenous injection of ondansetron should not exceed 8 mg with infusion for at least 15 minutes. After the initial dose of 8 mg, it is possible to continue the use of 2 doses of 8 mg, which are administered by infusion for 15 minutes at intervals between infusions for at least 4 hours.

Patients with renal failure

There is no need to change the dosage regimen or route of administration for the patients with impaired renal function.

Patients with hepatic failure

Among the patients with moderate and severe liver function impairment, the clearance of Emeton is significantly reduced,  while the half-life of the serum increases. For such patients, the maximum daily dose of the medicine should not exceed 8 mg.

Patients with disturbed metabolism of spartein / debrisokvin

The half-life of ondansetron among the patients with impaired metabolism of spartein and debrisokvin remains unchanged. In such patients, re-administration leads to the same medicine concentration as in patients with undivided metabolism. Therefore, the dosage change or the frequency of input is not required.

Postoperative nausea and vomiting

Adults

To prevent  postoperative nausea and vomiting, the recommended dose of Emeton is 4 mg as a single intramuscular or slow intravenous injection during anesthesia.

To treat postoperative nausea and vomiting, the recommended single dose of Emeton is 4 mg in the form of intramuscular or slow intravenous injection.

Children and adolescents (aged from 1 month to 17 years old)

For prevention and treatment of postoperative nausea and vomiting among children who are operated under general anesthesia, Emeton can be administered at a dose of 0.1 mg / kg body weight (maximal - up to 4 mg) by slow intravenous injection (at least 30 seconds) before, during, after anesthesia or after surgery.

Elderly patients

The experience of  Emeton use for the prevention and treatment of postoperative nausea and vomiting among the elderly people is limited, however, Emeton is well tolerated by patients aged over 65 years old  wo undergo chemotherapy.

Patients with renal failure

There is no need to change the dosage regimen or route of administration for patients with impaired renal function.

Patients with hepatic failure

Among the patients with moderate and severe liver function impairment, the clearance of Emeton is significantly reduced, while the half-life of the serum  increases. For such patients, the maximum daily dose of the medicine should not exceed 8 mg.

Patients with disturbed metabolism of spartein / debrisokvin

The half-life of ondansetron among the patients  with metabolic disorders of spartein and debrisokvin  remains unchanged. Among such patients, re-administration leads to the same medicine concentration as among the patients with undamaged metabolism. Therefore, the dosage change or the frequency of input is not required.

Instructions for use.

Ampoules with Emeton do not contain preservatives and should be used immediately after opening; the remaining solution must be destroyed.

Ampoules with Emeton can not be autoclaved.

Compatibility with other fluids for intravenous injection

Solutions for intravenous infusion should be prepared immediately before infusion. However, it has been established that ondansetron solution remains stable for 7 days at room temperature (up to 25 ° C) in daylight or in a refrigerator when dissolved in the following  media: 0.9% sodium chloride solution, glucose solution 5%, mannitol solution 10%, Ringer's solution, 0,3% solution of potassium chloride and 0,9% solution of sodium chloride, 0,3% solution of potassium chloride and a solution of glucose 5%.

It has been established that ondansetron  retains stability when  used in polyethylene and glass vials. It is known that ondansetron diluted with 0.9% sodium chloride or 5% glucose maintains stability in polypropylene syringes. It is also proven that stability in polypropylene syringes is maintained during the dilution of ondansetron with other recommended solutions.

In case of need for prolonged storage, the dilution should be carried out under appropriate aseptic conditions.

Compatibility with other medicines

Emeton can be administered as an intravenous infusion at the  rate of 1 mg / hour. With the Y-like injecter together with Emeton at concentrations of ondansetron from 16 to 160 μg / ml (i.e., 8 mg / 500 ml or 8 mg / 50 ml respectively), the following may be administered:

- cisplatin at a concentration of up to 0.48 mg / ml, for 1-8 hours;

- 5-fluorouracil in a concentration of up to 0.8 mg / ml (eg 2.4 g in 3 liters or 400 mg in 500 ml) at a rate of not more than 20 ml / hour. A higher concentration of 5-fluorouracil may result in precipitation of ondansetron. The solution for infusion of 5-fluorouracil may contain up to 0.045% magnesium chloride, in addition to other compatible excipients;

- carboplatin at a concentration of 0.18 mg / ml to 9.9 mg / ml (for example from 90 mg in 500 ml to

990 mg in 100 ml) for 10-60 minutes;

- etoposide at a concentration of 0.14 mg / ml to 0.25 mg / ml (for example from 72 mg in 500 ml to 250 mg in 1 liter) for 30-60 minutes;

- ceftazidime in a dose of 250 mg to 2 g diluted in water for injections (for example, 2.5 ml per 250 mg or 10 ml per 2 g of ceftazidime) as an intravenous bolus injection for 5 minutes;

- cyclophosphamide in a dose of 100 mg to 1 g, diluted in water for injections (5 ml per 100 mg cyclophosphamide), as an intravenous bolus injection for 5 minutes;

- doxorubicin in a dose of 10 mg to 100 mg, diluted in water for injections (5 ml per 10 mg doxorubicin), as an intravenous bolus injection for 5 minutes;

- dexamethasone in a dose of 20 mg in the form of a slow intravenous injection for 2-5 minutes (with simultaneous administration of 8 mg or 16 mg of ondansetron dissolved in 50-100 ml of injectable solution) for approximately 15 minutes. Since these drugs are compatible, they can be administered in one drop, and concentration of dexamethasone phosphate in the solution (in the form of sodium salt) will be from 32 μg to 2.5 mg in 1 ml, and ondansetron concentration will be  from 8 μg to 1 mg in 1 ml.

Adverse reactions

The side effects listed below are classified according to the organs and systems and the frequency of its occurrence. Frequency of occurrence is divided into the following categories: very common (≥1 / 10), common (≥1 / 100 and <1/10), uncommon (≥1 / 1000 and <1/100), rare (≥1 / 10,000 and <1 / 1,000), very rare (<1 / 10,000).

The side effects listed below are classified according to the organs and systems and the frequency of its occurrence.

From the immune system: immediate-type hypersensitivity reactions, sometimes severe, up to anaphylaxis.

From the nervous system: headache; convulsions, motor disorders (including extrapyramidal reactions such as occlusive crisis, dystonic reactions and dyskinesia without sustained clinical consequences); dizziness predominantly during rapid intravenous administration of the medicine.

From the vision organs: transient visual disturbances (clouding in the eyes), mainly during intravenous administration; transient blindness, mainly during intravenous use. In most cases, blindness lasts for 20 minutes.

From the cardiac system: arrhythmias, chest pain (with depression of the segment ST or without it), bradycardia; prolongation of QT interval (including ventricular jerking / flickering (Torsade de Pointes).

From the blood vessels: feeling of warmth or tides; hypotension

From the respiratory system and the chest organs: hiccups.

From the digestive tract: constipation.

From the hepatobiliary system: asymptomatic elevation of liver function parameters.

These cases are observed predominantly among patients treated with chemotherapeutic medicines containing cisplatin.

From the skin and subcutaneous tissue: toxic rashes, including toxic epidermal necrolysis.

General disorders: local reactions in the area of ​​intravenous administration.

According to data from post-registration observation, such side effects are known.

From the cardiovascular system: pain and discomfort in the breast, extrasystoles, tachycardia, including ventricular and supraventricular tachycardia, atrial fibrillation, palpitation, syncope, ECG changes.

Hypersensitivity reactions: anaphylactic reactions, angioneurotic edema, bronchospasm, anaphylactic shock, itching, skin rash, urticaria.

From the nervous system: disturbance of walking, chorea, myoclonus, restlessness, burning sensation, protrusion of the tongue, diplopia, paresthesia.

General disorders and local reactions: fever, pain, redness, burning at the injection site.

Other: hypokalemia.

Overdose

Data about overdose of ondansetron are not sufficient. In most cases, the symptoms are similar to those described among patients who administered the recommended doses (see. section "Adverse Reactions").

Ondansetron prolongs QT interval in dose-dependent form. In case of overdose, ECG monitoring is recommended.

Among the overdose expressing is reported visual disturbances, severe constipation, hypotension, vazovahalni manifestations of transient AV-block II degree. In all cases, these phenomena completely eliminated.

A specific antidote does not exist, therefore, in cases of overdose, symptomatic and supportive therapy should be used.

Application of  ipecacuanha to treat overdose of ondansetron is not recommended because its action can not occur through antiemetic influence of ondansetron.

Use during pregnancy or breastfeeding

Ondansetron is not used during these periods because of limited data of the safety of its use in pregnant and lactating women.

Ondansetron is able to penetrate breast milk. If the use of the medicine is necessary, breastfeeding should be stopped.

Children

The medicine is prescribed for children aged from 6 months for chemotherapy and from 1 month  for the prevention and treatment of postoperative nausea and vomiting.

Precautions for use

During the treatment of patients with hypersensitivity to other selective 5HT3 receptor antagonists hypersensitivity reactions were observed.

Ondansetron in the dose-dependent form extends the QT interval (see section “Pharmacological Properties”). Additionally, according to postmarketing surveillance reports, cases of torticollis (Torsade de Pointes) with ondansetron using were reported.

The use of ondansetron among patients with congenital QT prolongation syndrome should be avoided.

Ondansetron should be used with caution in the treatment of patients who have or may have  delayed QT interval prolongation, including patients with electrolyte imbalance, congestive heart failure, bradyarrhythmia, or patients treated with other drugs that may cause QT interval prolongation or electrolyte imbalance . Before starting the application, hypocalemia and hypomagnesaemia should be corrected.

After simultaneous use of ondansetron and other serotonergic medicines, serotonin syndrome has been described (see section "Interaction with other medicines and other types of interactions"). If concomitant treatment with ondansetron and other serotonergic medicines is clinically justified, appropriate follow-up of the patient is recommended.

Since ondansetron weakens intestinal motility, careful monitoring of patients with signs of subacute intestinal obstruction during the use of Emeton is required.

Among patients undergoing adrenocortical surgeries, the use of ondansetron to prevent nausea and vomiting may mask the onset of bleeding. Therefore, such patients should be carefully supervised after applying ondansetron.

Effects on ability to drive and use machines

Ondansetron has no sedative effect, but the profile of side effects of the medicine should be taken into account when driving motor vehicles or working with other mechines.

Interaction with other medicinal products and other forms of interaction

Ondansetron does not accelerate or inhibit the metabolism of other medicines when used simultaneously. Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lignocaine, thiopental or propofol.

Ondansetron is metabolized by various enzymes of the cytochrome P450 of liver: CYP3A4, CYP2D6 and CYP1A2. Due to the variety of metabolic enzymes of ondansetron, inhibition or decreased activity of one of them (eg, genetic deficiency of CYP2D6) under normal conditions is compensated by other enzymes and will not have any effect or influence on the overall clearance of creatinine will be negligible.

Ondansetron should be used with due caution in combination with medicines that prolong the QT interval and / or cause electrolyte imbalance (see section "Application features").

Apomorphine

The use of ontasetron with apomorphine hydrochloride is contraindicated, as there have been cases of severe hypotension and loss of consciousness during co-administration.

Phenytoin, carbamazepine and rifampicin

Among patients treated with potential CYP3A4 inducers (eg, phenytoin, carbamazepine and rifampicin), ondansetron clearance is increased and its concentration in the blood decreases.

Serotoninergytics (e.g., SSRIs and SRINs).

Serotonin syndrome (including changes in mental status, autonomic instability and neuromuscular disorders) has been described after concomitant use of ondansetron and other serotonergic medicines, including selective serotonin reuptake inhibitors (SIZZS) and serotonin reuptake inhibitors and norepinephrine (SIRNs) (see section " Application features").

Tramadol

According to a small number of clinical studies, ondansetron can reduce the analgesic effect of tramadol.

The use of Emeton with other medicines that extends the QT interval may result in an additional extension of this interval. The co-administration of Emeton with cardiotoxic medicines (eg, anthracyclines) may increase the risk of arrhythmia (see section " Application features ").

Pharmacological properties

Pharmacodynamics.

Ondansetron is a potent highly selective antagonist of 5HT3 (serotonin) receptors. The medicine prevents or eliminates nausea and vomiting caused by cytotoxic chemotherapy and / or radiation therapy, as well as postoperative nausea and vomiting. The ondansetron mechanism of action  is not fully studied. Probably, the medicine blocks the occurrence of a vomitting reflex, showing an antagonistic effect on  5HT3 receptors that are localized in the neurons of both the peripheral and central nervous system. The medicine does not reduce the psychomotor activity of the patient and does not have a sedative effect.

Pharmacokinetics.

When administrationed in intramuscular way, peak concentrations in blood plasma is reached within 10 minutes. The volume of distribution after parenteral administration among adults is 140 liters. The main part of the administered dose is metabolized in the liver. Less than 5% of the medicine is excreted unchanged with the urine. The half-life is approximately 3 hours (in elderly patients - 5 hours). Binding to plasma proteins - 70-76%.

Among patients with moderate renal insufficiency (clearance of creatinine 15-60 ml / min), both systemic clearance and the volume of ondansetron distribution are reduced, resulting in a small and clinically insignificant increase in the half-life of the medicine. The pharmacokinetics of ondansetron is virtually unchanged among patients with severe renal failur on chronic hemodialysis. Among patients with chronic severe hepatic failure, the systemic clearance of ondansetron decreases markedly with an increase of half-life (15-32 hours).

Pharmaceutical characteristics

Basic physical and chemical properties: clear, colorless or slightly colored liquid.

Incompatibility

Ondansetron should not be mixed in the same syringe or infusion solution with other medicines, unless specified in the section " Posology and method of administration".

Shelf life

2 years.

Unused ampoule content should be discarded, it shall not be stored for its further use.

Storage conditions

Store in original package at the temperature not above 25 °С.

Keep away from children.

Packaging

2 or 4 ml in the ampoules No. 5.

Prescription category

Following the doctor’s prescription.

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Materials on the medicine

No materials available.

Calculation of dose

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