Pharmacological properties
Pharmacodynamics. antiemetic. The mechanism of action is due to competitive highly selective blockade of central and peripheral 5HT3 serotonin receptors (receptors of the critical zone, vomiting center). Suppresses the vomiting reflex, eliminating and preventing nausea during the use of cytotoxic chemotherapeutic agents, radiation therapy, in the postoperative period. With repeated use, slows down peristalsis and the passage of contents through the intestines.
Pharmacokinetics. With i / v administration at a dose of 0.15 mg / kg body weight in adults under 75 years of age, C max in blood plasma is on average about 100 ng / ml, in people over 75 years of age - 170 ng / ml. With i / v infusion of 32 mg over 15 min, C max reaches 264 ng / ml. With i / m administration, C max of ondansetron in blood plasma (about 25 ng / ml) is observed 10 min after injection.
When taken orally, the drug is well absorbed in the gastrointestinal tract, bioavailability is about 60% due to the effect of the first passage through the liver. C max ondansetron in blood plasma is achieved after 1.5-1.7 hours. Food intake prolongs the absorption period by 17%, without affecting C max. Binding to plasma proteins is 70-76%.
The main part of the administered dose (85-90%) is hydroxylated in the liver with the participation of cytochrome P450 to compounds of the indole cycle, and then conjugated with glucuronic and sulfuric acids. The total volume of distribution is 1.9 l/kg of body weight, T ½ depending on age is 3.5-5.5 h, total clearance is 5.9 ml / (min · kg). The drug is excreted from the body by the kidneys, with 5% of the administered dose excreted unchanged. Pharmacokinetic parameters of ondansetron do not change with its repeated use.
In children and in people with liver damage, the total clearance decreases, in elderly patients T ½ and the total clearance of the drug increase. In patients with moderate renal insufficiency (creatinine clearance - 15-60 ml / min) the systemic clearance and volume of distribution of ondansetron are reduced, resulting in a clinically insignificant slight increase in T ½ of the drug. In women, C max and bioavailability of the drug are higher, and clearance and volume of distribution are lower than in men.
Indication
Prevention and elimination of nausea and vomiting during cytotoxic chemotherapy (initial and repeated courses, including the use of cisplatin in high doses) and radiotherapy (irradiation of the whole body surface, partial single high-dose or daily irradiation of the abdominal area) in oncology. Prevention and elimination of nausea and vomiting in the postoperative period in general surgery, ophthalmology, etc.
Application
pills
When conducting cytostatic therapy, the dosage regimen is set individually depending on the severity of the vomiting reaction.
Moderate Emetogenic Chemotherapy and Radiation Therapy
Adults and children over 12 years of age are prescribed orally: initially 8 mg 1-2 hours before the start of antitumor therapy, followed by another 8 mg after 8-12 hours. To prevent late or prolonged nausea and vomiting after the first 24 hours of use of the drug, 8 mg should be continued every 12 hours. with partial high-dose irradiation of the abdominal area, 8 mg is prescribed every 8 hours. The drug is taken throughout the entire course of chemotherapy and radiation therapy, as well as 1-2 days (if necessary - 3-5 days) after its completion.
Highly emetogenic chemotherapy
Adults and children over 12 years of age are prescribed 24 mg of ondansetron orally (simultaneously with dexamethasone phosphate) 1-2 hours before the start of chemotherapy. For the prevention of late vomiting in the following days, 8 mg 2 times a day during the entire course of chemotherapy, as well as 5 days after its completion.
During chemotherapy in children aged 4-12 years, the drug is administered orally: initially 4 mg 3 times a day (30 minutes before the start of the course, then after 4 and 8 hours). For the prevention of late vomiting, 4 mg is prescribed every 8 hours for 1-2 days, then 4 mg 2 times a day throughout the course, as well as 5 days after its completion.
Postoperative nausea and vomiting
Adults and children over 12 years of age are prescribed 16 mg 1 hour before anesthesia. Children under 12 years of age are not prescribed.
The maximum daily dose of ondansetron is 32 mg, for patients with severe liver dysfunction - 8 mg.
Solution for injection
The drug in the form of a solution for injection can be administered i / m or i / v by a single slow injection or by infusion. To prepare the solution of ondansetron for infusion, you can use 0.9% sodium chloride solution, 5% glucose solution, Ringer's solution. Ondansetron solution for infusion is prepared immediately before administration; however, if necessary, it can be stored until fully used for no more than 24 hours at a temperature of 2-8 ° C. During the infusion, protection from light is not required (under normal lighting).
Emetogenic chemotherapy and radiation therapy
Adults are given a solution at a dose of 8 mg intravenously slowly immediately before chemotherapy.
Highly emetogenic chemotherapy
• a dose of 8 mg is administered intravenously slowly immediately before the course of chemotherapy, then 2 times intravenously slowly at a dose of 8 mg with an interval of 2-4 hours or intravenously drip at a dose of 1 mg/hour for 24 hours.
The choice of dosage regimen is set individually depending on the severity of the emetogenic effect.
Children can be given a single intravenous dose of 5 mg/m2 immediately before chemotherapy.
Postoperative nausea and vomiting
Adults: 4 mg may be administered as a slow IV or IM injection during induction of anesthesia. To prevent postoperative nausea and vomiting, a single 4 mg IM or slow IV injection is recommended.
Children: to prevent postoperative nausea and vomiting, a dose of 0.1 mg/kg body weight (maximum 4 mg) may be administered intravenously slowly before, during or after the onset of anesthesia. To prevent postoperative nausea and vomiting, a single dose of 0.1 mg/kg (maximum 4 mg) intramuscularly or intravenously slowly is recommended.
Contraindication
Hypersensitivity to the components of the drug; pregnancy (especially the first trimester) and breastfeeding; liver failure, abdominal surgery; the drug is not prescribed to children under 4 years of age during chemotherapy and radiation therapy, during anesthesia, tablets cannot be prescribed to children under 12 years of age, solution for injection - up to 2 years.
Side effects
From the side of the central nervous system: headache, dizziness, temporary impaired visual acuity (with rapid intravenous administration), spontaneous movement disorders, seizures, depression of the central nervous system function, paresthesia, weakness, extrapyramidal symptoms, fainting;
from the cardiovascular system: feeling of heat and rush of blood to the face, arrhythmia, tachycardia or bradycardia, arterial hypo- or hypertension;
from the digestive system: constipation, diarrhea, hiccups, dry mouth, transient increase in aminotransferase activity, liver failure;
allergic reactions: urticaria, bronchospasm, in rare cases - anaphylactic reactions;
others: cough, chest pain (angina-like), redness and burning at the injection site.
Special instructions
Breastfeeding should be discontinued during treatment with ondansetron.
When using the drug parenterally, it is not recommended to exceed a dose of 8 mg/day in patients with moderate to severe liver dysfunction.
In case of a very pronounced emetic reaction as a result of chemotherapy, the effectiveness of the drug can be increased by a single intravenous injection of corticosteroids (for example, 20 mg of dexamethasone sodium phosphate) before the start of chemotherapy.
It is prescribed with caution to patients who have a history of hypersensitivity reactions to other selective serotonin 5HT 3 receptor antagonists. The drug is used with caution and under close medical supervision in the treatment of patients with signs of subacute intestinal obstruction.
Interactions
Concomitant use of inhibitors of microsomal hepatic enzymes of the cytochrome p450 system may increase t½ and reduce the total clearance of the drug.
When used in combination with inducers of hepatic enzymes of the cytochrome P450 system (barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin, hydantoins, rifampicin, tolbutamide, etc.), the clinical efficacy of the drug may be reduced.
The drug in the form of an infusion solution with an ondansetron concentration of 16-160 μg/ml (8 mg/500 ml-8 mg/50 ml) can be administered through a Y-shaped catheter in combination with the following drugs:
• cisplatin at a concentration of up to 0.48 mg/ml for 1-8 hours;
• carboplatin at a concentration of 0.18-9.90 mg/ml for 10-60 min;
• fluorouracil in a concentration of up to 0.8 mg/ml at a rate of at least 20 ml/h, it should be borne in mind that higher concentrations of fluorouracil may cause precipitation of ondansetron;
• etoposide at a concentration of 0.14-0.25 mg/ml for 30-60 minutes;
• ceftazidime at a dose of 0.025-2 g, diluted with water for injection according to the manufacturer's recommendations, as an intravenous bolus injection over 5 min;
• cyclophosphamide at a dose of 0.1-1 g, diluted with water for injection according to the manufacturer's recommendations, as an intravenous bolus injection over 5 minutes;
• doxorubicin at a dose of 10-100 mg, diluted with water for injection according to the manufacturer's recommendations, as an intravenous bolus injection over 5 minutes;
• dexamethasone at a dose of 20 mg IV slowly over 2-5 minutes in combination with 8-32 mg of ondansetron in 50-100 ml of solution.
The drug should not be used in the same syringe or dropper with other medications.
Overdose
In case of overdose, side effects may occur. Treatment is discontinuation of the drug and symptomatic therapy aimed at supporting vital functions. There is no specific antidote.
Storage conditions
Tablets - in a dry, dark place at a temperature not exceeding 25 °C; ampoules - in a dark place at a temperature not exceeding 25 °C. Shelf life - 2 years.
Translation of the instructions can be
