Ondansetron solution for infection. 2 mg/ml on 2 ml, 4 ml No. 5

General characteristics. Structure:

Acting substance: ondancetron; 1 ml of solution contains 2 mg of an ondansetron (in the form of a hydrochloride dihydrate); excipients: citric acid monohydrate, sodium citrate, sodium chloride, water for injections. Main physical and chemical properties: transparent colourless liquid.

Pharmacological properties:

Pharmacodynamics. Ondansetron is the strong high-selection antagonist 5HT3 (serotoninovy) receptors. Drug warns or eliminates the nausea and vomiting caused by cytotoxic chemotherapy and/or radiation therapy and also postoperative nausea and vomiting. The mechanism of action of Ondansetron is up to the end not found out. Perhaps, drug blocks emergence of an emetic reflex, revealing antagonistic action concerning 5HT3-receptors which are localized in neurons both peripheral, and the central nervous system. Drug does not reduce psychomotor activity of the patient and does not render sedation.

Pharmacokinetics. At intramuscular introduction peak concentration in plasma is reached within 10 minutes. Distribution volume after parenteral administration at adults makes 140 l. The main part of the entered dose gives in to metabolism in a liver. With urine in not changed look less than 5% of drug are removed. An elimination half-life – about 3 hours (patients of advanced age have 5 hours). Linkng with proteins of plasma – 70-76%.
At patients with a renal failure of moderate degree (clearance of creatinine of 15 - 60 ml/min.) both the system clearance, and volume of distribution of Ondansetron what insignificant and clinically insignificant increase in an elimination half-life of drug is result of decrease. Ondansetron's pharmacokinetics practically does not change at the patients with a renal failure of heavy degree who are on a chronic hemodialysis (researches were conducted in a break between hemodialysis sessions). At patients with a chronic liver failure of heavy degree the system clearance of Ondansetron considerably decreases with increase in an elimination half-life (15-32 hours).

Indications to use:

Treatment of nausea and vomiting, caused by cytotoxic chemotherapy and radiation therapy.
Prevention and treatment postoperative nausea and vomitings.

Route of administration and doses:

The drug can be administered intravenously by a one-time slow injection or by short-term (within 15 min.) infusions.
Adults.
Emetogenny chemotherapy and radiation therapy.
The recommended intravenous or intramuscular dose of Ondansetron – 8 mg, in the form of a slow injection, just before treatment.
For the prevention of attacks of the late or delayed vomiting after the first 24 h it is necessary to continue use of drug in the form of tablets on 8 mg twice a day during the next 5 days after the termination of a course of antineoplastic therapy.
Vysokoemetogenny chemotherapy.
To the patients receiving vysokoemetogenny chemotherapy (for example, high doses of Cisplatinum), Ondansetron can be appointed in the form of a single dose of 8 mg, intravenously or intramusculary, just before chemotherapy. Doses more than 8 mg (to 32 mg) can be applied only in the form of intravenous infusion on 50–100 ml of 0,9% of solution of sodium of chloride or other corresponding solvent (see the section "Features of Use"); infusion has to last not less than 15 minutes.
Alternatively 8 mg of Ondansetron it can be entered in the form of a slow intravenous or intramuscular injection, just before chemotherapy, with further two times intravenous or intramuscular administration of 8 mg in 2 and 4 hours or continuous infusion of 1 mg/hour within 24 hours.
Ondansetron's efficiency at vysokoemetogenny chemotherapy can be increased by additional one-time intravenous administration of dexamethasone of sodium of phosphate in a dose of 20 mg, before chemotherapy.
For the prevention of attacks of the late or delayed vomiting after the first 24 h it is necessary to continue use of drug in the form of tablets on 8 mg twice a day during the next 5 days after the termination of a course of antineoplastic therapy.
Children (aged from 4 years).
To children aged from 4 years Ondansetron in a dose of 5 mg/sq.m of a body surface can be appointed in the form of a one-time intravenous injection, just before chemotherapy, with further use of tablets of Ondansetron in 12 hours. Oral administration can last 5 more days after end of a course of treatment.
Patients of advanced age.
Ondansetron is well had by patients 65 years, irrespective of a dose, frequency and a way of administration of drug are more senior.
Postoperative nausea and vomiting.
Adults.
For prevention of postoperative nausea and vomiting the recommended Ondansetron's dose makes 4 mg, in the form of a one-time intramuscular or slow intravenous injection during introduction to an anesthesia.
For treatment of postoperative nausea and vomiting the recommended single dose of Ondansetron makes 4 mg in the form of an intramuscular or slow intravenous injection.
Children.
For prevention and treatment postoperative nausea and vomitings at children whom operate under the general anesthesia Ondansetron it is possible to enter in a dose 0,1 mg/kg of body weight (as much as possible – to 4 mg) in the form of a slow intravenous injection to, into time, after introduction to an anesthesia or after operation.
Patients of advanced age.
Experience of use of Ondansetron for prevention and treatment of postoperative nausea and vomiting at people of advanced age is limited, however drug is well transferred by patients 65 years, receiving chemotherapy are more senior.

Features of use:

Use during pregnancy or feeding by a breast. Ondansetron is not recommended to apply during pregnancy.
In need of use of drug in the period of a lactation it is necessary to stop feeding by a breast.

Children. Apply at children aged from 4 years.
Special security measures.
At treatment of patients with manifestation of hypersensitivity to other selection antagonists of 5HT3-receptors hypersensitivity reactions were observed.
As Ondansetron weakens an intestines peristaltics, careful observation of patients with signs of subacute impassability of intestines is necessary during its use.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Does not influence.

Patients with a renal failure.
There is no need for change of the mode of a dosage or a way of purpose of drug to patients with a renal failure.
Patients with a liver failure.
At patients with average and heavy abnormal liver functions Ondansetron's clearance considerably decreases, and the elimination half-life from blood serum increases. For such patients the maximum daily dose of drug should not exceed 8 mg.

Side effects:

On the frequency of emergence are divided into such categories: very often (≥1/10), it is frequent (≥1/100, and <1/10), infrequently (≥1/1 000 and <1/100), is rare (≥1/10 000 and <1/1 000), is very rare (<1/10 000).
Immune system.
Seldom: reactions of immediate hypersensitivity (from easy to heavy degree), an anaphylaxis.
Nervous system.
Very often: headache.
Often: spasms, motive disturbances (including extrapyramidal reactions, such as okulogirny crisis, dystonic reactions and dyskinesia without resistant clinical effects).
Seldom: dizziness during bystry intravenous administration of drug.
Frustration from an organ of sight.
Seldom: the fast-taking place eye frustration (opacification in eyes), mainly during intravenous administration.
Very seldom: the fast-passing blindness, mainly during intravenous use. In most cases the blindness passes within 20 minutes.
Heart.
Infrequently: arrhythmias, pain in heart (with a depression of a segment of ST or without it), bradycardia.
Vessels.
Often: feeling of heat or rush of blood.
Infrequently: arterial hypotension.
Respiratory system and bodies of a chest cavity.
Infrequently: hiccups.
Digestive tract.
Often: lock.
Gepatobiliarny system.
Infrequently: asymptomatic increase in indicators of function of a liver.
These cases are observed, mainly, at patients who are treated by the chemotherapeutic drugs containing Cisplatinum.
General frustration.
Often: local reactions in the field of intravenous administration.

Interaction with other medicines:

Ondansetron does not accelerate and does not slow down metabolism of other drugs at use, simultaneous with it. Ondansetron does not interact with alcohol, temazepam, furosemide, tramadoly and propofoly.
Ondansetron is metabolized by enzymes of R-459 cytochrome of a liver: CYP3A4, CYP2D6 and CYP1A2. Thanks to a variety of enzymes of metabolism of Ondansetron braking or decrease of the activity of one of them (for example, genetic deficit of CYP2D6) in usual conditions is compensated by other enzymes and will not influence or influence on the general clearance of creatinine will be insignificant.
Phenytoinum, carbamazepine and rifampicin:
At patients who are treated by the potential inductors CYP3A4 Ondansetron's clearance increases and its concentration in blood decreases.
Tramadol:
According to a small amount of clinical trials, Ondansetron can reduce analgetichesky effect of a tramadol.
Interaction with other liquids for intravenous injections.
Solutions for intravenous injection need to be prepared just before infusion. But it is established that Ondasetron's solution keeps firmness within 7 days at the room temperature (to 25 °C) at daylight or in the refrigerator at dissolution in such environments: sodium chloride of 0,9%, glucose of 5%, Mannitolum of 10%, Ringer's solution, potassium chloride of 0,3% and sodium chloride of 0,9%, potassium chloride of 0,3% and glucose of 5%.
It is established that Ondansetron keeps stability also when using polyethylene and glass bottles. It was shown that Ondansetron, divorced 0,9% sodium chloride or 5% glucose, keeps stability in polypropylene syringes. It is proved also that stability in polypropylene syringes remains at Ondansetron's cultivation by other recommended solutions.
In need of long storage of drug dissolution has to be carried out in the corresponding aseptic conditions.

Interaction with other drugs.
Ondansetron can be appointed in the form of intravenous infusion with a speed of 1 mg/hour. Through
Y-like injektor together with Ondansetron at Ondansetron's concentration from 16 to 160 mkg/ml (that is 8 mg / 500 ml or 8 mg / 50 the ml respectively) can be entered:
- Cisplatinum in concentration to 0,48 mg/ml, within 1-8 hours;
- 5-ftoruratsit in concentration up to 0,8 mg/ml (for example, 2,4 g in 3 l or 400 mg in 500 ml) with a speed no more than 20 ml/hour. Higher concentration of a 5-ftoruratsil can cause Ondansetron's precipitation. Solution for infusions of a 5-ftoruratsil may contain up to 0,045% of magnesium chloride in addition to other fillers which are compatible;
- карбоплатин in concentration from 0,18 mg/ml to 9,9 mg/ml (for example, from 90 g in 500 ml to 990 mg in 100 ml) within 10–60 minutes;
- этопозид in concentration from 0,14 mg/ml to 0,25 mg/ml (for example, from 72 mg in 500 ml to 250 mg in 1 l) within 30–60 minutes;
- the ceftazidime in a dosage from 250 mg to 2 g divorced in water for injections (for example, 2,5 ml on 250 mg or 10 ml on 2 g of a ceftazidime), in the form of an intravenous bolyusny injection within 5 minutes;
- the cyclophosphamide in a dosage from 100 mg to 1 g divorced in water for injections (5 ml on 100 mg of cyclophosphamide), in the form of an intravenous bolyusny injection within 5 minutes;
- the doxorubicine in a dosage from 10 mg to 100 mg divorced in water for injections (5 ml on 10 mg of doxorubicine), in the form of an intravenous bolyusny injection within 5 minutes;
- dexamethasone in a dosage of 20 mg, in the form of a slow intravenous injection within 2-5 minutes (at simultaneous introduction of 8 mg or 32 mg of Ondansetron dissolved in 50–100 ml of injection solution), within about 15 minutes. As these drugs are compatible, they can be entered through one dropper, at the same time in solution of concentration of dexamethasone of phosphate (in the form of sodium salt) will make from 32 mkg to 2,5 mg in 1 ml, and Ondansetron - from 8 mkg to 1 mg in 1 ml.

Contraindications:

Hypersensitivity to any components of drug. Pregnancy and period of feeding by a breast. Children's age up to 4 years.

Overdose:

Data on Ondansetron's overdose are not enough. In most cases symptoms similar on described at patients to whom entered the recommended doses (see. "Side reactions"). The specific antidote against drug does not exist therefore in cases of overdose the symptomatic and maintenance therapy has to be applied.

Storage conditions:

To store in the place protected from light at a temperature not above 30 °C. To store in the place, unavailable to children.

Period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

On 2 ml or 4 ml in ampoules, on 5 ampoules in a pack.