Ondansetron

General characteristics. Structure:

Active ingredient: 4 mg or 8 mg of an ondansetron.

Antiemetic of direct action.

Pharmacological properties:

Pharmacodynamics. Pharmacological action - antiemetic. On competitive type vysokoselektivno blocks central (chemoceptors of a trigger zone, the emetic center) and peripheral serotoninovy 5-HT3-receptors. Suppresses an emetic reflex, eliminates and warns the vomiting mediated by release of serotonin at use of cytostatic protivoblastomny means, radiation therapy in the postoperative period. At repeated introduction slows down a peristaltics and passing of contents on intestines.

Pharmacokinetics. Later in/in introductions of 0,15 mg/kg of Cmax  makes for age groups 19-40, 61-74, 75 and more years of 102, 106 and 170 ng/ml, T1/2  — 3,5; 4,7 and 5,5 h, plasma Cl — 0,381; 0,319 and 0,262 l/h respectively; at in 15-minute infusion of 32 mg of Cmax  reaches 264 ng/ml, T1/2  — 4,1 h Cmax  at introduction in oil is registered 10 min. later. In a GIT it is well absorbed. Meal for 17% extends the absorption period, without influencing C
max and time of its approach.

Bioavailability — 56% (effect of "the first passing"), time of achievement of Cmax  (its size is proportional to a dose) — 1,7 p. T1/2  — 3 h. Contacts proteins of a blood plasma for 70–76% (respectively 10-500 ng/ml of in vitro), partially gets into erythrocytes. Intensively is exposed to transformations (only 5% are removed with urine in not changed look). The main part of the entered dose is hydroxylated in a liver before connections of an indole cycle, in then conjugates with glucuronic or sulfuric acids.

Women have a speed and duration of absorption from a GIT, absolute bioavailability and indicators of plasma are higher, and the clearance and level of distribution are lower, than at men. Against the background of severe damages of a liver the plasma clearance decreases in 5 times (T1/2  is 20,6 h) moderated — twice (T1/2  — 9,2 h).

Indications to use:

Nausea and vomiting (prevention and treatment) at cytotoxic chemotherapy, radiation therapy, in the postoperative period.

Route of administration and doses:

In/in, in oil, inside, rektalno.

Cytostatic therapy: the choice of the mode of dosing is defined by an emetogennost of antineoplastic therapy. For adults the daily dose makes, as a rule, 8-32mg. Efficiency of an ondansetron can be increased by way of a glucocorticoid, one-time in/in introductions (for example 20 mg of dexamethasone) prior to the beginning of chemotherapy.

For the prevention of the delayed vomiting arising in 24 h after the beginning himio-or radiotheraphy, it is recommended to continue administration of drug inside on 8 mg each 12 h or rektalno on 16 mg of 1 times a day within 5 days.

To children 2 years — 5 mg/m in/in just before the beginning of a course with the subsequent intake in a dose of 4 mg in 12 h are more senior; after the termination of a course it is recommended to continue treatment on 4 mg 2 times a day inside within 5 days.

Prevention of postoperative nausea and vomiting: the adult — in a single dose of 4 mg in oil or in/in (slowly) at the beginning of an anesthesia or inside in a dose of 16 mg for 1 h prior to the beginning of an anesthesia; to children 2 years — only parenterally in a single dose of 0,1 mg/kg (as much as possible to 4 mg) in the form of slow in/in an injection to or after anesthesia are more senior.

Stopping of the developed postoperative nausea and vomiting: adult — 4 mg in oil or in/in; to children 2 years — 0,1 mg/kg (to 4 mg) in/in slowly are more senior.

In oil into the same body part ондансетрон it can be entered in the dose which is not exceeding 4 mg!

At the expressed disturbance of functions of a liver the clearance of an ondansetron substantially decreases, T1/2 from plasma therefore it is not necessary to exceed a daily dose (8 mg) increases.

Features of use:

Use at pregnancy and feeding by a breast. At pregnancy (especially the first 3 months) it is possible only if the advantage for mother exceeds potential risk for a fruit.

Category of action on a fruit on FDA — B. For the period of treatment it is necessary to stop breastfeeding. It is unknown whether it is excreted ондансетрон in breast milk of women. It is found in milk of the lactating rats.

Special observation of patients with signs of subacute impassability of intestines is necessary (because of increase in time of passing through a large intestine).

It is not recommended to enter in one syringe with other drugs. Injection forms part only with the recommended solutions. Let's combine with infusion solutions of sodium and potassium of chloride, a dextrose, mannitol, Ringera. Before their introduction it is necessary to be convinced of lack of coarse particles and discolorations (if the container allows); the precipitated calcium superphosphate which is contained on ampoule walls (does not influence activity and safety), dissolve by vigorous stirring; ampoules do not autoclave, protect from light influence.

Side effects:

From bodies of a GIT: lock/diarrhea, dryness in a mouth, a hiccups, tranzitorny increase in level of nuclear heating plant and ALT.

From a nervous system and sense bodys: a headache, dizziness, spontaneous motive frustration and spasms, visual acuity disturbance, extrapyramidal disturbances (at parenteral use).

From cardiovascular system and blood (a hemopoiesis, a hemostasis): a faint, thorax pain, in some cases with ST segment depression, bradycardia, arrhythmia, arterial hypotension.

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

Others: fever, feeling of heat, rush of blood to the person, a hypopotassemia, a hypercreatinemia, local reactions (pain, reddening and burning in the place of an injection); burning in the field of an anus and a rectum (suppositories).

Interaction with other medicines:

As ондансетрон it is metabolized by fermental system of a liver (P450 cytochrome), care at combined use with inductors of isoenzymes of CYP2D6 and CYP3A of P450 cytochrome (barbiturates, carbamazepine, griseofulvin, nitrous oxide, a papaverine, phenylbutazone, Phenytoinum and probably other hydantoins, rifampicin, Tolbutamidum) is required, and also with inhibitors of isoenzymes P450 CYP2D6 and CYP3A (Allopyrinolum, antibiotics macroleads, MAO antidepressants-inhibitors, chloramphenicol, Cimetidinum, estrogensoderzhashchy oral contraceptives, diltiazem, Disulfiramum, erythromycin, valproic acid, sodium Valproatum, флуконазол, ftorkhinolona, an isoniazid, кетоконазол, ловастатин, metronidazole, омепразол, propranolol, quinidine, quinine, verapamil).

Contraindications:

Hypersensitivity, children's age — for rectal administration (up to 2 years — for intake and parenteral administration).

Overdose:

Symptoms: strengthening of expressiveness of side reactions.

Treatment: symptomatic therapy. The specific antidote is unknown.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and 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:

Tablets of 4 mg, and 8 mg. On 20 tablets in each blister, on one, two or three blisters in cardboard packaging.