Ondansetron - instructions for use, dose, side effects, contraindications

Excipients: (carboxymethyl starch sodium - 7,036 mg, "microcrystalline cellulose - 95.860 mg, lactose monohydrate 16,105 mg, magnesium stearate 0.999 mg) to a tablet weighing 125 mg (excluding the coating); (hypromellose - 3,100 mg, titanium dioxide 0.199 mg, polysorbate 80-0.695 mg, quinoline dye, yellow (E-104) 0.006 mg) to prepare a coated tablet weighing 129 mg.

Description:

Round biconvex tablets, covered with a film coating of yellow color. On the cross-section, two layers are visible: yellow and white. The determination is made visually.

Pharmacotherapeutic group:An antiemetic, a serotonin receptor antagonist

ATX: & nbsp

A.04.A.A.01 Ondansetron

Pharmacodynamics:

Ondansetron is a highly selective antagonist of serotonin 5-HT₃receptors. Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in the concentration of serotonin, which by activation of afferent fibers of the vagus nerve, containing receptors 5-HT₃, causes a vomitive reflex. Selectively blocks serotonin 5-HT₃receptors of central neurons (vomiting center) and peripheral (gastrointestinal tract) of the nervous system that regulates the gag reflex. Does not disrupt the coordination of movements, does not cause sedation and reduced efficiency. Does not change the concentration of prolactin in the plasma.

Pharmacokinetics:

Ondansetron is completely absorbed in the gastrointestinal tract after ingestion and is metabolized first pass through the liver. Bioavailability is about 60%. Maximum concentration (C_max) ondansetron in the blood plasma is achieved approximately 1.5 hours after ingestion and is approximately 30 ng / ml after taking the drug in a dose 8 mg. Bioavailability increases somewhat with simultaneous intake of food, but does not change when taking antacids. Binding to blood plasma proteins - 70-76%.

The distribution of the drug for oral administration, intravenous and intramuscular administration is the same. The volume of distribution when an equilibrium state is reached is about 140 liters. Half-life (T_1/2) is 3 hours, in elderly patients can reach 5 hours, and with severe hepatic insufficiency - 15-20 hours.From the systemic blood flow is eliminated, mainly as a result of metabolism in the liver, which occurs with the participation of several microsomal liver enzymes(CYP1A2, CYP2D6, CYP3A4). Absence of isoenzyme CYP2D6 does not affect the pharmacokinetics of ondansetron. In unchanged form, less than 5% of the administered dose is excreted in the urine. The pharmacokinetic parameters of ondansetron do not change when it is repeated.

Pharmacokinetics in special clinical cases

In children, the importance of clearance and volume of distribution depends on age. Correction of the dose taking into account the body weight of patients (from 0.1 mg / kg to 4 mg maximum) compensates for these changes and normalizes the system exposure of ondansetron in children.

In patients with moderate renal insufficiency (creatinine clearance 15-60 ml / min), both systemic clearance and volume of ondansetron distribution are reduced, resulting in a small and clinically insignificant increase T_1/2 (up to 5.4 hours).

The pharmacokinetics of ondansetron practically does not change in patients with severe renal dysfunction, which are on chronic hemodialysis.

In patients with severe impairment of liver function, the systemic clearance of ondansetron drastically decreases, resulting in an increase in the half-life of it (up to 15-32 h)and bioavailability with oral intake reaches 100% due to a decrease in presystemic metabolism.

In elderly people there is a slight increase in bioavailability to 65% and a half-life of up to 5 hours.

The distribution of ondansetron depends on sex, women have a higher intake absorption, as well as a lower systemic clearance and volume of distribution.

Indications:

- Prevention and management of nausea and vomiting caused by cytostatic chemotherapy or radiotherapy;

- prevention and relief of nausea and vomiting in the postoperative period.

Contraindications:

- Hypersensitivity to ondanan adherent or other components of the drug;

- pregnancy and the period of breastfeeding;

- children under 3 years (for dosage 4 mg) and children's age up to 12 years (for dosage 8 mg)

Carefully:

Hereditary lactose intolerance, congenital insufficiency of lactase or glucose-galactose malabsorption.

Dosing and Administration:

The drug is intended for oral administration. The choice of the dosage regimen is determined by the severity of the emetogenic effect of the antitumor therapy.

For adults, the daily dose, as a rule, is 8-24 mg.

The following modes are recommended:

With a moderate expression of the emetogene effect of chemotherapy and radiotherapy

Adults and children over 12 years of age are prescribed 8 mg ondansetron for 1-2 hours before the start of the main therapy with subsequent 8 mg orally through 12 hours.

Children from 4 to 11 years of age are prescribed 4 mg of ondansetron 30 minutes before the start of the main therapy, followed by a further 4 mg inside every 8 hours. Data on the use of radiotherapy in children under 12 years are absent.

With high expression of emetogenic chemotherapy and radiotherapy

The recommended adult dose (danfor childrenly) is 24 mg concomitantly with dexamethasone inside at a dose of 12 mg per 1- 2 hours before the start of chemotherapy.

To prevent late or prolonged vomiting

Adults should continue taking the drug inside at a dose of 8 mg 2 times a day for 5 days after the end of the main therapy.

The drug is given to the children in a dose 5 mg / m² surface of the body intravenously for at least 15 minutes immediately before the start of chemotherapy,with the subsequent ingestion of 4 mg ondansetron after 12 hours; treatment is recommended to continue at a dose of 4 mg 2 times a day inside for 5 days.

Prevention of postoperative nausea and vomiting

Adults prescribe 16 mg orally for 1 hour before the start of general anesthesia.

Children to prevent and stoppostoperative nausea and vomiting ondansetron is administered only parenterally.

Elderly patients

A dose change is not required.

Patients with impaired renal function

Correction of a daily dose or frequency of ondansetron is not required.

Side effects:

Impaired nervous system: headache, dizziness, spontaneitymotor disorders and convulsions;

Disorders from the side of the organ of vision: temporary violation of visual acuity.

Violations from gastro-intestinalwespecial path: hiccough, dry mouth, diarrhea, constipation.

Disorders from the side of the liver: asymptomatic transient increase in the concentration of aminotransferases in blood serum.

Heart Disease: pain in the chest, in some cases with depression of the segment S-T, arrhythmias, bradycardia.

Vascular disorders: lowering of blood pressure. Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis.

Laboratory and instrumental data: hypokalemia, hypercreatininaemia.

Other: "tide" of blood to the face, a feeling of heat.

Overdose:

Symptoms: visual impairment, constipation, lowering of arterial pressure and vasovagal episode with atrioventricular blockade of the II degree. In all cases, the phenomena are completely reversible.

Treatment: conduct symptomatic and supportive therapy, a specific antidote is not known.

Interaction:

As ondansetron is metabolized by the enzyme system (cytochrome P450) of the liver, caution is required when combined:

- with inducers of cytochrome P450 (isoenzymes CYP2D6 and CYP3A) (barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, dinitrogen oxide, papaverine, phenylbutazone, phenytoin (probably other hydantoins), rifampicin, tolbutamide);

with inhibitors of cytochrome P450 (isoenzymes CYP2D6 and CYP3A) (allopurinol,

macrolide antibiotics, antidepressants - MAO inhibitors, chloramphenicol, cimetidine, oral contraceptives containing estrogens, diltiazem, disulfiram, valproic acid, sodium valproate, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil).

Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide and propofol.

Ondansetron can reduce the anesthetic effect of tramadol.

Special instructions:

Ondansetron should not be given to children with a body surface area of less than 0.6 m². Ondansetron It can not be used to prevent and treat postoperative nausea and vomiting in children after surgery on the abdominal organs.

In patients who had previously used other 5-HT selective antagonists₃-receptor reactions were observed with hypersensitivity, with the application of ondansetron, similar reactions can also develop.

As ondansetron can slow intestinal motility, patients with signs of intestinal obstruction after using the drug require regular monitoring.

Effect on the ability to drive transp. cf. and fur:In case of side effects from the nervous system, patients are advised to refrain from managementcar and other mechanisms, as well as other activities that require concentration of attention, stress of psychomotor functions.

Form release / dosage:Tablets, film-coated, 4 mg.

Packaging:

For 10 tablets in a contour mesh box made of a polyvinyl chloride light barrier film and aluminum foil foil. 1 or 2 contour packs together with instructions for use in the pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002318

Date of registration:22.09.2011

Expiration Date:Unlimited

The owner of the registration certificate:FARMSTANDART-UFAVITA, JSC FARMSTANDART-UFAVITA, JSC Russia

Manufacturer: & nbsp

FARMSTANDART-UFAVITA, JSC Russia

Representation: & nbspPHARMSTANDART-Ufa-VITA, JSCPHARMSTANDART-Ufa-VITA, JSC

Information update date: & nbsp07.06.2017

Illustrated instructions

Instructions

Ondansetron (Ondansetron)