Ondansetron

General characteristics. Structure:

Active substance: an onlansetrona gilrokhlorit лигидрат in terms of ондансетрон the basis - 2 mg.
Excipients: citric acid, sodium citrate trekhaameirnny (sodium nitrate). sorbite (сорйитоп), water for injections.

Description: colourless or almost colourless transparent or with easy opalescence liquid.

Pharmacological properties:

Pharmacodynamics. Ondansetron is the selection antagonist of receptors 5-NTZ (serotonin). Medicines for cytostatic chemotherapy and radiotheraphy can cause increase in level of serotonin which by activation of the vagal afferent fibers containing receptors 5-NTZ causes an emetic reflex.

Ondansetron slows down emergence of an emetic reflex by blockade of receptors 5-NTZ at the level of neurons of both the central, and peripheral nervous system. Apparently, the prevention and treatment postoperative and caused cytostatic himio-and radiotheraphy of vomiting and nausea is based on this mechanism of action.

Pharmacokinetics. At intramuscular introduction peak concentration in plasma is reached within 10 minutes. Drug is exposed to metabolism in a liver. Linkng with proteins of plasma makes 70-76%. With urine in not changed look less than 5% of drug are allocated.

At parenteral administration the elimination half-life makes about 3 h, at elderly patients can reach 5 hours, and at the expressed liver failure of-15-20 hours. At damage of kidneys (the renal clearance is less than 15 ml/min.) the elimination half-life increases for 4-5 hours, but this increase has no clinical value.

Indications to use:

The prevention and elimination of nausea and vomiting, caused by cytostatic chemotherapy and radiotheraphy, and also postoperative nausea and vomiting.

Route of administration and doses:

Cytostatic therapy.

The choice of the mode of dosing is defined by an emetogennost of antineoplastic therapy.

For adults the daily dose, as a rule, makes 8-32 mg, the following modes are recommended:
At moderate emetogenny chemotherapy of an ipa of radiotheraphy: 8 mg intravenously struyno slowly or intramusculary, just before the beginning of therapy;

At vysokoemetgenny chemotherapy:

- 8 mg intravenously struyno slowly just before the beginning of chemotherapy, and then two more intravenous injections on 8 mg, each of which is carried out in 2-4 hours;

- continuous 24-hour infusion of drug in a dose of 24 mg with a speed of 1 mg/hour;-16-32 mg divorced in 50-100 ml of the corresponding infusion solution in the form of an infusion 15-minutnoa, just before the beginning of chemotherapy. Efficiency of an ondansetron can be increased by one-time intravenous administration of a glucocorticoid (for example, 20 mg of fosfornonatriyevy salt of dexamethasone) prior to the beginning of chemotherapy.

Children

To children is more senior than 2 years drug is appointed in a dose of 5 mg/sq.m of a body surface intravenously, just before the beginning of chemotherapy.

Prevention of postoperative nausea and vomiting

The adult enter a single dose of 4 mg intramusculary or intravenously struyno, slowly at the beginning of an anesthesia. For stopping of the arisen nausea and vomiting intramuscular slow intravenous administration of an ipa 4 mgpreparat is recommended. Intramusculary into the same body part ондансетрон it can be entered in the dose which is not exceeding 4 mg! To children to prevention of postoperative nausea and vomiting ондансетрон it is applied parenterally in a single dose of 0,1 mg/kg (as much as possible to 4 mg) in the form of a slow intravenous injection to or after anesthesia.

For treatment of the developed postoperative nausea and vomiting at children slow intravenous administration of a single dose of drug of 0,1 mg/kg is recommended (as much as possible to 4 mg).

Concerning prevention and treatment of postoperative nausea and vomiting children under 2 years have no sufficient experience.

Elderly patients
 Change of a dosage is not required.
Patients with damages of kidneys and a liver
 At damage of kidneys it is not required to change a usual daily dose and frequency of administration of drug.
 At damage of a liver the clearance of an onlansetron substantially decreases. and time of its semi-removal from plasma therefore it is necessary to lower a dose to 8 mg a day increases.
 The following solutions can be applied to cultivation of injection solution: 0,9% sodium chloride solution,
5% glucose solution,
Ringer's solution,
0,3% solution of potassium chloride and 0,9% sodium chloride solution,
0,3% solution of potassium chloride and 5% glucose solution.

Features of use:

At patients who at use of other selection antagonists have earlier 5-HT3 receptors hypersensitivity reactions were observed, at Ondansetron's use similar reactions can also develop. As Ondansetron can cause a lock, patients with signs of impassability of intestines after use of drug demand regular observation. Infusion solution has to be prepared just before use.

In case of need ready infusion solution can be stored before use as much as possible within 24 hours at a temperature of 2-8 °C. During performing infusion of protection against light it is not required; divorced injection solution keeps the stability at least within 24 hours at natural light or normal lighting.

Side effects:

Allergic reactions: small tortoiseshell, bronchospasm. laryngospasm. Quincke's disease, anaphylaxis.

From the alimentary system: a hiccups, dryness in a mouth. лиарея. a lock, an inogl asymptomatic prekholyashy increase in level of aminotransferases in blood serum.

From cardiovascular system: thorax pains, in some cases with ST segment depression. arrhythmias, bralikardiya, lowering of arterial pressure.

From a nervous system: headache, dizziness, spontaneous motive frustration and spasms.

Local reactions: pain, burning and reddening in an injection site.

Others: rush of blood to the person, feeling of heat, temporary disturbance of visual acuity, a hypopotassemia.

Interaction with other medicines:

As ондансетрон it is metabolized by fermental system (P450 cytochrome) of a liver, care at combined use is required:
with the enzymatic inductors P450 (CYP2D6 and CYP3A) (barbiturates, carbamazepine, каризопродол, глютетимид, griseofulvin, nitrous oxide, papaverine, phenylbutazone, Phenytoinum (possibly, and other hydantoins), rifampicin, Tolbutamidum);
with inhibitors of P450 enzymes (CYP2D6 and CYP3A) (Allopyrinolum, makrolidny antibiotics, antidepressants - MAO inhibitors, chloramphenicol, Cimetidinum, the oral contraceptives containing estrogen, diltiazem, Disulfiramum, valproic acid, sodium Valproatum, erythromycin, fluconazole, ftorkhinolona, an isoniazid, кетоконазол, ловастатин, metronidazole, омепразол, propranolol, quinidine, quinine, verapamil).

Contraindications:

Hypersensitivity to any component of drug, pregnancy and a lactation.
Children's age up to 2 years (safety and efficiency of use was not studied).

Overdose:

In cases of alleged overdose symptomatic therapy is shown. The specific antidote is not known.

Storage conditions:

List B. In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for injections on 4 mg / 2 ml and 8 mg / 4 ml (2 mg/ml) in ampoules of colourless neutral glass.

On 5 ampoules in a blister strip packaging. On 1 or 2 blister strip packagings together with the application instruction in a cardboard pack.