Ondansetron

General characteristics. Structure:

International and chemical names: ondansetron, (3RS) - 9-metil-3-[(2-methyl-1H-imidazole-1-silt) - methyl] - 1,2,3,9-TETRAGIDRO-4H-KARBAZOL-4-ON a hydrochloride a dihydrate; main physical and chemical properties: transparent, colourless liquid; structure: 1 ml of solution contains an ondansetron of a hydrochloride of a dihydrate in terms of ондансетрон 2 mg; excipients: citric acid, sodium citrate, sodium chloride, water for injections.

Pharmacological properties:

Pharmacodynamics. Antiemetic. The mechanism of action is caused by competitive high-selection blockade of the central and peripheral 5HT3 receptors of serotonin (receptors of a trigger zone, the emetic center). Suppresses an emetic reflex, eliminating and warning nausea at use of cytotoxic chemotherapeutic means, radiation therapy, during the postoperative period. At repeated use slows down a peristaltics and passing of contents on intestines.

Pharmacokinetics. At intravenous administration in a dose of 0,15 mg/kg adult up to 75 years the maximum concentration in blood makes, on average, about 100 ng/ml, at persons 75 years – 170 ng/ml are more senior. At intravenous infusion of 32 mg within 15 minutes the maximum concentration reaches 264 ng/ml. At intramuscular introduction the maximum concentration of an ondansetron in blood is registered in 10 minutes after an injection and makes about 25 ng/ml. Linkng with proteins of plasma - 70-76%. The main part of the entered dose (85-90%) is hydroxylated in a liver with participation of P 450 cytochrome before connections of an indole cycle, and then conjugates with glucuronic and sulfuric acids. The total amount of distribution makes 1,9 l/kg, an elimination half-life depending on age - from 3,5 to 5,5 hours. Drug is excreted from an organism by kidneys, at the same time 5% of the entered dose are removed in not changed look. Pharmacokinetic parameters of an ondansetron do not change at its repeated introduction.
At children, and also at persons with damages of a liver the general clearance decreases, at elderly patients the elimination half-life and the general clearance of drug increases. At patients with a moderate renal failure (clearance of creatinine of 15-60 ml/min.) the system clearance and volume of distribution of an ondansetron what clinically insignificant small increase in an elimination half-life of drug is result of are reduced. Women have a level of the maximum concentration and bioavailability of drug is higher, and the clearance and level of distribution are lower, than at men.

Indications to use:

Prevention and treatment of nausea and vomiting, caused cytotoxic himio-or radiation therapy; postoperative nausea and vomiting.

Route of administration and doses:

The drug can be administered intramusculary or intravenously, by a one-time slow injection or by infusion. For infusion 0,9% solution of sodium of chloride, 5% glucose solution, Ringer's solution can be applied to preparation of solution of an ondansetron. Solution of an ondansetron for infusional introduction is prepared just before introduction; however in case of need it is possible to store it before full use no more than 24 hours at a temperature of 2-8 °C. During performing infusion protection against light at normal lighting is not required.
Emetogenny chemotherapy and radiation therapy
The adult appoint solution in a dose of 8 mg intravenously, slowly, just before carrying out chemotherapy.
Vysokoemetogenny chemotherapy
 a single dose of 8-32 mg intravenously, slowly, just before carrying out chemotherapy; at introduction in a dose higher than 8 mg Ondansetron it is necessary to dissolve in 50-100 ml 0,9% of solution of sodium of chloride or other compatible solution for intravenous administration and to carry out infusion not less than 15 minutes;
 a dose of 8 mg intravenously, slowly, just before carrying out a course of chemotherapy, then 2 times intravenously, slowly, in a dose of 8 mg with an interval of 2-4 hours or intravenously kapelno in a dose of 1 mg/h within 24 hours.
The choice of the mode of a dosage is established individually, depending on degree of manifestation of emetogenny effect.
Children can appoint in the form of a one-time intravenous injection in a dose 5 ^mg/sq.m just before carrying out chemotherapy.
Postoperative nausea and vomiting
Adults. Purpose of 4 mg in the form of slow intravenous administration or an intramuscular injection is possible during anesthesia induction. For elimination of development of postoperative nausea and vomiting single introduction of 4 mg intramusculary or intravenously slowly is recommended.
Children. For prevention of postoperative nausea and vomiting it is possible to appoint in a dose 0,1mg/kg (at most 4 mg) in the form of a slow intravenous injection to, in time or after the beginning of anesthesia. For elimination of development of postoperative nausea and vomiting single introduction in a dose of 0,1 mg/kg (at most 4 mg) intramusculary or intravenously slowly is recommended.

Features of use:

At appointment patients with the moderated and expressed abnormal liver functions are not recommended to exceed a dose of 8 mg/days. At very expressed emetic reaction as a result of chemotherapy efficiency of drug can be increased by one-time intravenous administration of glucocorticoids (for example 20 mg of dexamethasone) prior to the beginning of chemotherapy.
With care appoint to the patients having in the anamnesis of reaction of hypersensitivity to other selection antagonists of serotoninovy 5HT3-receptors. With care and under careful medical observation use drug at treatment of patients with signs of subacute impassability of intestines.

Side effects:

From the central nervous system: a headache, dizziness, temporary disturbance of visual acuity (at bystry intravenous administration), spontaneous motive frustration, attacks of spasms, oppression of the central nervous system, paresthesia, weakness, extrapyramidal symptomatology, a syncope;
from cardiovascular system: feeling of heat and rush of blood to the person, arrhythmia, tachycardia or bradycardia, hypotension or hypertensia;
from the alimentary system: a lock, diarrhea, a hiccups, dryness in a mouth, tranzitorny increase in activity of aminotransferases, insufficiency of function of a liver;
allergic reactions: a small tortoiseshell, a bronchospasm, in isolated cases – anaphylactic reactions;
others: cough, thorax pains (anginous type), reddening and burning in the place of an injection.

Interaction with other medicines:

Drug in the form of infusion solution at concentration of an ondansetron of 16-160 mkg/ml (8 mg / 500 ml - 8 mg / 50 ml) can be entered through Y figurative catheter jointly with the following drugs:
 Cisplatinum in concentration to 0,48 mg/ml within 1-8 hours;
 карбоплатин in concentration of 0,18-9,90 mg/ml within 10-60 minutes;
 5-ftoruratsit in concentration up to 0,8 mg/ml with a speed not less than 20 ml/h, at the same time it is necessary to consider that higher concentration of a 5-ftoruratsil can cause precipitation of an ondansetron;
 этопозид in concentration of 0,14-0,25 mg/ml within 30-60 minutes;
 the ceftazidime in a dose of 0,025-2,0 g divorced water for injections according to recommendations of the producer in the form of an intravenous bolyusny injection within 5 minutes;
 the cyclophosphamide in a dose of 0,1-1,0 g divorced water for injections according to recommendations of the producer in the form of an intravenous bolyusny injection within 5 minutes;
 the doxorubicine in a dose of 10-100 mg divorced water for injections according to recommendations of the producer in the form of an intravenous bolyusny injection within 5 minutes;
 dexamethasone in a dose of 20 mg intravenously, slowly, within 2-5 minutes together with 8-32 mg of an ondansetron in 50-100 ml of solution.
Drug should not be used in one syringe or in one dropper with other medicines.
Simultaneous use of inhibitors of microsomal liver enzymes of system of P 450 cytochrome can increase time of semi-removal and reduce the general clearance of drug.
At simultaneous use with inductors of microsomal liver enzymes of system of P 450 cytochrome (barbiturates, carbamazepine, каризопродол, глютетимид, griseofulvin, nitrous oxide, a papaverine, phenylbutazone, Phenytoinum and other hydantoins, rifampicin, Tolbutamidum) decrease in clinical performance of drug is possible.

Contraindications:

Hypersensitivity to drug components. Insufficiency of function of a liver; surgeries on an abdominal cavity; pregnancy (especially I trimester); lactation period; children's age: at himio-and radiation therapy – up to 4 years; at anesthesia – up to 2 years.

Overdose:

At overdose the aggravation of the symptoms described in the section "Side effect" is possible.
Treatment: the drug withdrawal and symptomatic therapy directed to maintenance of the vital functions. There is no specific antidote.

Storage conditions:

To store in protected from light, the place, unavailable to children, at a temperature not above 25 °C.

Period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

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