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

Ondansetron is a selective antagonist 5-HT₃- receptors (serotonin). Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in serotonin levels, which by activation of vagal afferent fibers containing 5-HT₃ - receptors, causes a vomitive reflex. Selectively blocks serotonin 5NT₃receptors of neurons of the central and peripheral nervous system, endings n.vagus in the intestine and in the centers of the central nervous system (mainly the bottom of the IV ventricle), regulating the implementation of emetic reflexes. Does not disrupt the coordination of movements, does not cause sedation and reduced efficiency. It has anxiolytic activity. 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. Time to reach the maximum concentration (T_C_max) ondansetron in the blood plasma is achieved approximately 1.5 hours after ingestion. Bioavailability increases somewhat with simultaneous intake of food, but does not change when taking antacids. The connection with plasma proteins is 70-76%.

The volume of distribution is 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 enzymes (CYP1A2, CYP2D6, CYP3A4). Absence of enzyme 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.

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 a longer half-life (up to 15-32 h), and oral bioavailability reaches 100% due to a decrease in presystemic metabolism.

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:

- Pincreased sensitivity to ondansetron or other components of the drug;

- pregnancy and the period of breastfeeding;

- children's age until 12 years (for a given dosage).

Pregnancy and lactation:Contraindicated.

Dosing and Administration:

Cytostatic therapy

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.

With moderate emetogenic chemotherapy or radiotherapy:

Adults and children over 12 years of age appoint 8 mg orally 1-2 hours before the start of the main therapy, then 8 mg through 12 hours.

Data on the use of radiotherapy in children under 12 years are absent.

With highly emeticogenic chemotherapy:

Recommended dose for adults (no data for use in children) is 24 mg concomitantly with dexamethasone inside at a dose 12 mg for 1-2 hours before the start of chemotherapy.

To prevent late or prolonged vomiting that occurs after 24 hours, continue taking ondansetron in a dose 8 mg twice daily for 5 days.

Prevention of postoperative nausea and vomiting

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

Children for preventing and arresting postoperative nausea and vomiting ondansetron is used exclusively parenterally.

Elderly patients

Dosage adjustments are not required.

Patients with impaired renal function

Change the usual daily dose and the frequency of administration of the drug is not required.

Patients with impaired hepatic function

The daily dose of ondansetron should not exceed 8 mg per day.

Patients with a slow metabolism of sparteine / debrisokwin.

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

Side effects:

Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis.

From the digestive system: hiccough, dry mouth, diarrhea, constipation, sometimes asymptomatic transient increase in the level of aminotransferases in the serum.

From the side of the cardiovascular system: pain in the chest, in some cases with depression of the segment S-T, arrhythmias, bradycardia, lowering blood pressure.

From the nervous system: headache, dizziness, spontaneous movement disorders and convulsions.

Other: "tide" of blood to the face, a feeling of heat, a temporary violation of visual acuity, rarely - hypokalemia, hypercreatininaemia.

Overdose:

In cases of suspected overdose, symptomatic therapy is indicated. The specific antidote is unknown. In case of an overdose of ondansetron, the use of ipecacuanas is not recommended, as it is unlikely that this drug will be effective during the antiemetic activity of ondansetron.

Interaction:

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

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

- with inhibitors of enzymes P₄₅₀(CYP2D6 and CYP3A) - allopurinol, macrolide antibiotics, antidepressants (monoamine oxidase inhibitors (MAO)), chloramphenicol, cimetidine, estrogen-containing oral contraceptives, diltiazem, disulfiram, valproic acid and its salts, erythromycin, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil).

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

Special instructions:

Patients who had previously had allergic reactions to other selective blockers 5NT₃-receptors, have an increased risk of their development against the background of ondansetron.

Ondansetron can slow the motility of the large intestine, and therefore, its appointment to patients with signs of intestinal obstruction requires regular monitoring.

Due to the presence of lactose in the patient with rare hereditary diseases, such as galactose intolerance, lactose deficiency or glucose-galactose malabsorption, it is not recommended to take the drug.

Form release / dosage:

Tablets, film-coated 8 mg.

Packaging:For 10 tablets in a contoured cell package made of a polyvinylchloride light barrier film and aluminum foil foil. One or two contour packs together with instructions for use in a pack of cardboard.

Storage conditions:

List B.

At a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children!

Shelf life:

2 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-009399/09

Date of registration:23.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

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

Information update date: & nbsp07.06.2017

Illustrated instructions

Instructions

Ondansetron (Ondansetron)