Setronon

General characteristics. Structure:

Active agent: ондансетрон 2 mg (in the form of a dihydrate hydrochloride)
excipients: sodium citrate, citric acid monohydrate, sodium chloride, water for injections.

Description: Solution: transparent colourless solution.

Pharmacological properties:

Pharmacodynamics. Ondansetron is the selection antagonist of receptors 5HT3 (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-HT3 causes an emetic reflex. Ondansetron slows down emergence of an emetic reflex by blockade of receptors 5-HT3 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.
Ondansetron does not influence concentration of prolactin in blood serum.

Pharmacokinetics. At intramuscular introduction the maximum concentration is measured within 10 min. after an injection. Distribution of an ondansetron is identical at intramuscular and intravenous administration. After intake the maximum concentration of an ondansetron in a blood plasma is reached approximately in 1,5 h. Absolute bioavailability after intake makes about 60%. 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.
Both after intake, and at parenteral administration the elimination half-life makes about 3 h, at elderly patients can reach 5 hours, and at the expressed liver failure - 15-22 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 expressiveness of emetogenny action of the carried-out antineoplastic therapy.

For adults the daily dose, as a rule, makes 8-32 mg, the following modes are recommended:
At moderate emetogenny chemotherapy or radiotheraphy:

• 8 mg intravenously struyno slowly or intramusculary, just before the beginning of therapy;

• 8 mg inside in 1-2 hours prior to therapy, then 8 more mg inside in 12 hours later began therapies,
At vysokoemetogenny chemotherapy:

• 8 mg intravenously struyno (slowly) just before the beginning of chemotherapy, and then two more intravenous jet 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 15-minute infusion, 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 dexamethasone) prior to the beginning of chemotherapy; at intake for strengthening of effect the single dose can be increased to 24 mg and is appointed along with 12 mg of dexamethasone for 1-2 h prior to carrying out chemotherapy.
For the prevention of the delayed vomiting arising in 24 hours after the beginning himio-or radiotheraphy, it is recommended to continue drug use inside on 8 mg 2 times a day within 5 days.
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 with the subsequent intake in a dose of 4 mg in 12 hours; after the termination of chemotherapy it is recommended to continue treatment on 4 mg twice a day inside within 5 days.

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, or appoint 16 mg inside in 1 hour prior to the beginning of an anesthesia.

For stopping of the arisen nausea and vomiting intramuscular or slow intravenous administration of 4 mg of drug 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 exclusively 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 in time 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 ondansetron substantially decreases, and time of its semi-removal from plasma therefore it is not necessary to exceed a daily dose in 8 mg a day increases.

The following solutions can be applied to cultivation of injection solution:

• 0,9% chloride sodium solution,

• 5% dextrose solution,

• Ringer's solution,

• 0,3% solution of potassium of chloride and 0,9% chloride sodium solution,

• 0,3% solution of potassium of chloride and 5% dextrose solution.

Features of use:

At patients at whom earlier at use of other selection antagonists of 5HT3-receptors, hypersensitivity reactions were observed at use of an ondansetron similar reactions can also develop.
As ондансетрон causes 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 artificial lighting.
In the presence of a lactose intolerance it is necessary to consider that 4 mg the tablet contains 59,25 mg of lactose, 8 mg - 118,5 mg respectively.
Ondansetron does not break ability to drive the car and to work with moving mechanisms, and also does not possess sedation.

Side effects:

Allergic reactions: small tortoiseshell, bronchospasm, laryngospasm, Quincke's disease, anaphylaxis.
From the alimentary system: a hiccups, dryness in a mouth, diarrhea, a lock, sometimes asymptomatic passing increase in level of aminotransferases in blood serum.
From cardiovascular system: thorax pains, in some cases with a depression of a segment of ST, arrhythmia, bradycardia, a 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; seldom - a hypopotassemia (connection with administration of drug is unambiguously not established).

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, a dinitrogene oxide, a papaverine, phenylbutazone, Phenytoinum (it is probable also 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, флуконазол, ftorkhinolona, an isoniazid, кетоконазол, ловастатин, metronidazole, омепразол, propranolol, quinidine, quinine, verapamil).
• Does not enter interaction with alcohol, temazepam, furosemide, tramadoly and propofoly.

Ondansetron in concentration of 16-160 mkg/ml pharmaceutical is compatible to the following medicines which can be entered through a Y-shaped injector:

• cisplates (in concentration to 0,48 mg/ml) during 1-8 h;

• 5-ftoruratsit (in concentration to 0,8 mg/ml with a speed of 20 ml/h - higher concentration can cause settling out of an ondansetron);

• карбоплатин (in concentration of 0,18-9,9 mg/ml within 10-60 min.);

• этопозид (in concentration of 0,14-0,25 mg/ml within 30-60 min.);

• a ceftazidime (in a dose of 0,25-2,0 g, in the form of an intravenous bolyusny injection within 5 min.);

• cyclophosphamide (in a dose from 0,1-1,0 g, in the form of an intravenous bolyusny injection within 5 min.);

• doxorubicine (in a dose of 10-100 mg, in the form of an intravenous bolyusny injection within 5 min.);

• dexamethasone: perhaps intravenous administration of 20 mg of dexamethasone slowly, within 2-5 min. Medicines can be entered through one dropper, at the same time in solution of concentration of dexamethasone of sodium of phosphate can make from 32 mkg to 2.5 mg/ml, an ondansetron - from 8 mkg to 1 mg/ml.

Contraindications:

• Hypersensitivity to any component of drug
• Pregnancy and period of feeding by a breast.
• 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. Solution for injections: at a temperature not above 25 °C in the place unavailable to children protected from light. Tablets: at a temperature not above 30 °C, in the place unavailable to children. The Tablet period of validity - 3 years. Solution for injections - 2 years. Drug should not be used 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 in colourless glass ampoules. On 5 ampoules in a cardboard pack with the enclosed application instruction.