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: tablets of a round form, coated yellow color, with a biconvex surface, on cross section are visible two layers; structure: 1 tablet contains an ondansetron of a hydrochloride of a dihydrate in terms of ондансетрон 4 mg or 8 mg; excipients: starch prezhelatinizirovanny, lactoses monohydrate, cellulose microcrystallic, magnesium stearate, Opadry II Yellow.

Pharmacological properties:

Pharmacodynamics. Antiemetic. The mechanism of action is caused by competitive high-selection blockade of the central and peripheral 5HT3 receptors of serotonin. 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. Drug is well absorbed in digestive tract, bioavailability makes about 60%, in connection with effect of "the first passing" through a liver. The maximum concentration of an ondansetron in blood is reached in 1,5-1,7 hours. Meal extends the absorption period for 17%, without influencing the maximum concentration. Linkng with proteins of plasma - 70-76%.
The main part of the entered dose (85-90%) is hydroxylated in a liver with participation of P450 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, the general clearance - 5,9 ml / (мин*кг). 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 multiple dose.
At children, and also at persons with damages of a liver the general clearance decreases, at patients of old age 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 elimination of nausea and vomiting at cytotoxic chemotherapy (initial and repeated courses, including use of high doses of Cisplatinum) and radiation therapy (radiation of all body surface, partial single high-dose or daily exposition of abdominal area) in oncology. Prevention and elimination of nausea and vomiting during the postoperative period in the general surgery, ophthalmology, etc.

Route of administration and doses:

When performing cytostatic therapy the mode of dosing is set individually, depending on degree of manifestation of emetic reaction.
Moderate emetogenny chemotherapy and radiation therapy
To adults and children 12 years inside are more senior appoint: originally 8 mg in 1-2 hours prior to antineoplastic therapy with the subsequent reception of 8 more mg in 8-12 hours. For prevention of late or long nausea and vomiting after the first 24 hours it is necessary to continue use of drug on 8 mg each 12 hours. At partial high-dose radiation of abdominal area appoint 8 mg each 8 hours. Drug is accepted during all course himio-and radiation therapy, and also 1-2 days (if necessary - 3-5 days) after its termination.
Vysokoemetogenny chemotherapy
To adults and children 12 years inside are more senior appoint 24 mg of an ondansetron (along with dexamethasone phosphate) in 1-2 hours prior to the beginning of chemotherapy. For prevention of late vomiting in the next days on 8 mg 2 times a day during all course of chemotherapy, and also 5 days after its termination.
At chemotherapy at children of 4-12 years inside appoint: originally on 4 mg 3 times a day (in 30 minutes prior to the beginning of a course, then in 4 and 8 hours). For prevention of late vomiting appoint 4 mg each 8 hours 1-2 days, then on 4 mg 2 times a day during all course, and also 5 days after its termination.
Postoperative nausea and vomiting
To adults and children 12 years are more senior appoint on 16 mg in 1 hour prior to anesthesia. To children up to 12 years do not appoint.
The maximum daily dose of an ondansetron makes 32 mg, for patients with moderate and heavy abnormal liver functions – 8 mg.

Features of use:

During treatment by Ondansetron feeding by a breast needs to be stopped.
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 of sodium of phosphate) prior to the beginning of chemotherapy.
With care to 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 to use drug at treatment of patients with signs of subacute impassability of intestines.

Side effects:

From the central nervous system: headache, dizziness, spontaneous motive frustration, attacks of spasms, oppression of the central nervous system, paresthesia, weakness, extrapyramidal symptomatology, 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).

Interaction with other medicines:

Simultaneous use of inhibitors of microsomal liver enzymes of system of P450 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 P450 cytochrome (barbiturates, carbamazepine, каризопродол, глютетимид, griseofulvin, nitrous oxide, a papaverine, phenylbutazone, Phenytoinum, hydantoins, rifampicin, Tolbutamidum, etc.) decrease in clinical performance of drug is possible.

Contraindications:

Hypersensitivity to drug components; pregnancy (especially I trimester); lactation period; children's age: at himio-and radiation therapy - up to 4 years, at anesthesia - up to 12 years; insufficiency of function of a liver, surgeries on an abdominal cavity.

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 dry, protected from light and 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 10 tablets in a blister strip packaging and a pack.