Prevention and treatment of nausea and vomiting caused by cytostatic chemotherapy and radiotherapy in adults
The choice of dosage regimen is determined by the emetogenicity of antitumor therapy and may vary at depending on the combinations of the regimens used for chemotherapy and radiotherapy.
Adults
The recommended dose is 8 mg, intravenously or intramuscularly immediately before chemotherapy or radiotherapy.
With highly emeticogenic chemotherapy, the maximum initial dose of ondansetron should be 16 mg in the form of a 15-minute infusion. A single intravenous dose of Zofran® should not exceed 16 mg.
The efficacy of ondansetron in high-emetogenic chemotherapy can be increased by a single intravenous injection of dexamethasone sodium phosphate at a dose of 20 mg before chemotherapy.
If intravenously administered at doses exceeding 8 mg but not more than the maximum 16 mg, Zofran® preparation should be diluted in 50-100 ml of a 0.9% solution of sodium chloride for injection or 5% of a solution of dextrose for injection before administration, and then administered for at least 15 minutes.When ondansetron is administered in doses not exceeding 8 mg, no dilution is required; in this case, the drug can be administered slowly intramuscularly or intravenously for at least 30 seconds. After the first dose of ondansetron is administered, two additional doses of intramuscular or intravenous 8 mg can be administered at intervals of 2-4 hours, or a continuous infusion of 1 mg / h for a maximum of 24 hours can be administered.
For treatment delayed or protracted vomiting after the first 24 hours, the use of Zofran® in medicinal forms for rectal or oral administration is recommended.
Special patient groups
Elderly patients
In the treatment of patients aged 65 years and older, all doses for intravenous administration should be diluted and administered in the form of a 15-minute infusion, and if necessary, reapplication should be introduced no earlier than 4 hours later.
Patients aged 65 to 74 years after the first dose of ondansetron 8 mg or 16 mg in the form of a 15-minute infusion you can enter 2 additional doses (not earlier than 4 hours) of 8 mg in the form of 15-minute infusion.
In patients aged 75 years and older, the first intravenous 15-minute Infusion should not exceed 8 mg.After the administration of the first dose of 8 mg, 2 additional doses may be administered as a 15-minute infusion (not earlier than 4 hours) for 8 mg.
Patients with impaired renal function
Correction of the daily dose, the frequency of dosing or the route of administration of ondansetron is not required.
Patients with impaired hepatic function
In patients with impaired liver function of moderate and severe severity, clearance of ondansetron is significantly reduced, half-life much increased.
In such patients, the daily dose of ondansetron should not exceed 8 mg.
Patients with a slow metabolism of sparteine-debrisoquine
In patients with a slow metabolism of sparteine-debrisoquine, the half-life of ondansetron is not changed. Consequently, upon repeated administration such patients ondansetron its concentration in plasma will not differ from that in the general population. Therefore, adjustments to the daily dose or ondansetron dosing frequency in this case not required.
Prevention and treatment of nausea and vomiting caused by cytostatic chemotherapy in children
Nausea and vomiting during chemotherapy in children and adolescents (aged 6 months to 18 years)
The dose of Zofran® in children is calculated on the basis of surface area or body weight.
In pediatric clinical trials Zofran® was used as an intravenous infusion after dissolving the drug in 25-50 ml of a 0.9% solution of sodium chloride or another compatible infusion solution in view 15 minutes infusion.
Calculation of the dose based on body surface area in children aged 6 months to 18 years for the prevention and treatment of nausea and vomiting, caused by chemotherapy
Ondansetron should be appoint as a single intravenous injection at a dose of 5 mg / m2 (not more than 8 mg) immediately prior to chemotherapy followed by oral after 12 hours. Taking Zofran® orally can be continued for another 5 days after the course of chemotherapy. When using the drug in this age group, do not exceed the dose used in adults.
Dose calculation table based on body surface area in children aged 6 months to 18 years for the prevention and treatment of nausea and vomiting caused by chemotherapy
| Body surface area | Day 1 | Day 2-6 |
| <0.6 m2 | 5 mg / m2 intravenously, followed by 2.5 ml syrup (2 mg ondansetron) after 12 h | 2.5 ml syrup (2 mg ondansetron) every 12 hours |
| ≥ 0.6 m2 and ≤ 1.2 m2 | 5 mg / m2 intravenously, then 5 ml of syrup or lyophilized tablets (4 mg ondansetron) after 12 h | 5 ml syrup or lyophilized tablets (4 mg ondansetron) every 12 h |
| > 1.2 m2 | 5 mg / m2 intravenously or 8 mg intravenously, followed by 10 ml of syrup or lyophilized tablets (8 mg ondansetron) after 12 h | 10 ml syrup or lyophilized tablets (8 mg ondansetron) every 12 h |
Calculation of dose based on body weight in children aged 6 months to 18 years for the prevention and treatment of nausea and vomiting caused by chemotherapy
The drug Zofran®, a solution for intravenous and intramuscular administration, should administered once intravenously immediately before the start of chemotherapy at a dose of 0.15 mg / kg. The dose for intravenous administration should not exceed 8 mg. On the first day, 2 additional doses may be administered at intervals of 4 hours, followed by taking Zofran® orally 12 hours later. Oral administration of Zofran® can continue for 5 days after chemotherapy. When using the drug in patients of this age group, do not exceed the doses used in adults.
Dose calculation table based on body weight in children aged 6 months to 18 years for the prevention and treatment of nausea and vomiting caused by chemotherapy
| Body mass | Day 1 | Day 2-6 |
| ≤10 kg | Up to 3 doses of 0.15 mg / kg intravenously, every 4 hours | 2.5 ml syrup (2 mg ondansetron) every 12 hours |
| > 10 kg | Up to 3 doses of 0.15 mg / kg intravenously, every 4 hours | 5 ml syrup or lyophilized tablets (4 mg ondansetron) every 12 h |
Prevention and treatment postoperative nausea and vomiting in adults and children
Adults
For prevention nausea and vomiting in the postoperative period, a single intramuscular or slow intravenous injection of Zofran® in a dose of 4 mg during anesthesia is recommended. For treatment nausea and vomiting in the postoperative period, Zofran® is administered once in a dose of 4 mg intramuscularly or slowly intravenously.
Special patient groups
Children and adolescents (aged 1 month to 18 years)
For prevention and treatment nausea and vomiting in the postoperative period in children who underwent surgery under general anesthesia, Zofran® can be used at a dose of 0.1 mg / kg (up to max. 4 mg) as a slow intravenous injection (at least 30 seconds) before, during or after an initial anesthesia or after an operation.
Elderly patients
There is limited experience with ondansetron for prevention and treatment postoperative nausea and vomiting in elderly patients, although ondansetron well tolerated by patients aged 65 years and older who are receiving chemotherapy.
Patients with impaired renal function
Correction of the daily dose, the frequency of dosing or the route of administration of ondansetron is not required.
Patients with impaired hepatic function
In patients with moderate to severe hepatic impairment, the clearance of ondansetron is significantly reduced, and the half-life much increased. The daily dose of ondansetron should not exceed 8 mg.
Patients with a slow metabolism of sparteine-debrisoquine
In patients with a slow metabolism of sparteine-debrisoquine PThe half-life of ondansetron is not changed. Consequently, with the repeated administration of such patients to ondansetron, its plasma concentration will not differ from that in the general population. Therefore, correction of the daily dose or ondansetron dosing frequency in this case is not required.
Pharmaceutical compatibility
The drug Zofran®, a solution for intravenous and intramuscular injection,must be used or diluted immediately after opening the ampoule. Any volume of the remaining solution must be disposed of.
Zofran® preparation, solution for intravenous and intramuscular injection, do not handle in an autoclave. The conducted studies of compatibility with the use of infusion bags from polyvinylchloride and systems for the introduction of polyvinylchloride showed that stability is ensured by using infusion bags made of polyethylene or glass vials of type 1.
The stability of the diluted Zofran®, a solution for intravenous and intramuscular administration, in an infusion solution of sodium chloride 0.9%, or dextrose 5% in syringes of polypropylene. Therefore, we can conclude about the stability in syringes of polypropylene Zofran®, a solution for intravenous and intramuscular injection, diluted with compatible infusion solutions. In accordance with the requirements of good pharmaceutical practice, solutions for intravenous administration should be prepared immediately prior to administration under appropriate sterile conditions.
Compatibility with infusion solutions
Pharmaceutical compatibility studies have shown that Zofran® Mr.The above infusion solutions remain stable for 7 days at room temperature (not above 25 ° C) under fluorescent lighting conditions or in a refrigerator at a temperature of 2-8 ° C:
- 0.9% solution of sodium chloride;
- 5% dextrose solution;
- Ringer's solution;
- 10% mannitol solution;
- 0.3% potassium chloride solution and 0.9% sodium chloride solution;
- 0.3% potassium chloride solution and 5% dextrose solution.
Compatibility with other drugs
Zofran® can be administered as an infusion at a rate of 1 mg / h from an infusion bag or a syringe pump.
Zofran® can be administered via Y-port in an ondansetron concentration of 16 to 160 μg / mL (eg, 8 mg / 500 mL and 8 mg / 50 mL, respectively) concurrently with the drugs described below.
| Cisplatinum | In a concentration of up to 0.48 mg / ml (e.g., 240 mg in 500 ml) upon administration for 1 to 8 hours. |
| Fluorouracil | At a concentration of up to 0.8 mg / ml (for example, 2.4 g in 3 L or 400 mg in 500 ml) when administered at a rate of at least 20 ml / h (500 ml / 24 hours). Higher concentrations of fluorouracil may cause ondansetron to precipitate. Fluorouracil for infusions may contain up to 0.045% of chloride machines in addition to other excipients, but which is compatible. |
| Carboplatin | Concentrations range from 0.18 mg / ml to 9.9 mg / ml (eg, from 90 mg in 500 ml to 990 mg in 100 ml) with administration for 10 minutes to 1 hour. |
| Etoposide | Concentrations in the range of 0.144 mg / ml to 0.25 mg / ml (for example, from 72 mg in 500 ml to 250 mg in 1 L) upon administration for 30 minutes to 1 hour. |
| Ceftazidime | Doses in the range of 250 mg to 2000 mg reconstituted with water for long injections of the drug according to the instructions for use by manufacturers (eg, 2.5 ml per 250 mg and 10 ml per 2 g ceftazidime) and administered as an intravenous bolus injection for approximately 5 min. |
| Cyclophosphamide | Doses in the range of 100 mg to 1 g of water reconstituted long injections of the preparation in accordance with the manufacturer's instructions for use (5 ml per 100 mg cyclophosphamide) and administered as an intravenous bolus injection for approximately 5 minutes. |
| Doxorubicin | Doses in the range of 10 to 100 mg reconstituted with water for injection preparation in accordance with the manufacturer's instructions (5 ml per 10 mg doxorubicin) and administered as an intravenous bolus injection for approximately 5 minutes. |
| Dexamethasone | It is possible to administer dexamethasone sodium phosphate 20 mg in the form of a slow intravenous injection for about 2 to 5 minutes via Y-port, with the introduction of 8 to 16 mg of Zofran®, diluted in 50-100 ml in a compatible solution for infusions, for about 15 minutes. The compatibility of dexamethasone sodium phosphate and Zofran® was confirmed when these preparations were administered via the same administration system, which allowed the expected concentrations of 32 μg / ml to 2.5 mg / ml for dexamethasone sodium phosphate n from 8 m kg / ml to 1 mg / ml for ondansetron. |