Ondansetron
Prevention and treatment of nausea and vomiting caused by cytostatic chemotherapy and radiation therapy in adults
The choice of dosage regimen is determined by the emetogenicity of antitumor therapy and may differ depending on the combinations of chemotherapy and radiation therapy regimens used.
Adults
The recommended dose is 8 mg intravenously or intramuscularly immediately before starting chemotherapy or radiation therapy.
For highly emetogenic chemotherapy, the maximum initial dose of ondansetron should be 16 mg as an intravenous infusion over 15 minutes. A single intravenous dose of ondansetron should not exceed 16 mg.
The effectiveness of ondansetron in highly emetogenic chemotherapy can be increased by a single intravenous dose of dexamethasone sodium phosphate 20 mg before chemotherapy.
When administered intravenously in doses exceeding 8 mg, but not more than the maximum dose of 16 mg, before administration, ondansetron should be diluted in 50-100 ml of 0.9% sodium chloride solution or 5% dextrose solution for injection, 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) over at least 30 seconds.
After the first dose of ondansetron, 2 additional doses of 8 mg intramuscularly or intravenously can be administered at intervals of 2 to 4 hours, or a continuous infusion at a rate of 1 mg/hour may be given for no more than 24 hours.
For the treatment of delayed or prolonged vomiting after the first 24 hours, it is recommended to take Ondansetron in dosage forms for rectal or oral administration.
Special patient groups
Prevention and treatment of nausea and vomiting caused by cytostatic chemotherapy in children
Nausea and vomiting during chemotherapy in children and adolescents (ages 6 months to 18 years)
The dose of Ondansetron in children is calculated based on surface area or body weight.
Ondansetron can be administered as an intravenous infusion after dissolution in 25-50 ml of 0.9% sodium chloride solution or other compatible infusion solution for at least 15 minutes.
Dose calculation based on body surface area in children 6 months to 18 years of age for the prevention and treatment of chemotherapy-induced nausea and vomiting Ondansetron should be given as a single intravenous injection at a dose of 5 mg/m2 (not to exceed 8 mg) immediately before treatment. chemotherapy followed by oral administration of the drug 12 hours after the chemotherapy session. Taking Ondansetron orally can be continued for another 5 days after the course of chemotherapy. When using the drug in this age category, the doses used in adults should not be exceeded.
Table 1. Dose calculation of ondansetron based on body surface area in children 6 months to 18 years of age for the prevention and treatment of chemotherapy-induced nausea and vomiting
| Body surface area | Day 1 | Days 26 |
| <0.6 m2 | 5 mg/m2 intravenously, then 2.5 ml syrup (2 mg ondansetron) 12 hours after chemotherapy | 2.5 ml syrup (2 mg ondansetron) every 12 hours |
| ≥0.6 and ≤1.2 m2 | 5 mg/m2 IV, then 5 ml syrup or lyophilized tablets (4 mg ondansetron) after 12 hours | 5 ml syrup or lyophilized tablets (4 mg ondansetron) every 12 hours |
| >1.2 m2 | 5 mg/m2 IV or 8 mg IV followed by 10 ml syrup or lyophilized tablets (8 mg ondansetron) after 12 hours | 10 ml syrup or lyophilized tablets (8 mg ondansetron) every 12 hours |
Dose calculation based on body weight in children 6 months to 18 years of age for the treatment of chemotherapy-induced nausea and vomiting
Ondansetron should be administered as a solution for intravenous or intramuscular administration as a single intravenous dose 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 should be given 4 hours apart, followed by oral ondansetron syrup 12 hours later. Oral ondansetron may be continued for 5 days after chemotherapy. When using the drug in patients of this age category, dosages used in adults should not be exceeded.
Table 2. Dose calculations based on body weight in children 6 months to 18 years of age for the treatment of chemotherapy-induced nausea and vomiting
| Body weight, kg | Day 1 | Days 2-6 |
| ≤10 | Up to 3 doses of 0.15 mg/kg IV every 4 hours | 2.5 ml syrup (2 mg ondansetron) every 12 hours |
| >10 | Up to 3 doses of 0.15 mg/kg IV every 4 hours | 5 ml syrup or lyophilized tablets (4 mg ondansetron) every 12 hours |
Elderly patients
When treating patients 65 years of age and older, all intravenous doses should be diluted and administered as a 15-minute infusion and, if necessary, re-administered no sooner than 4 hours later.
In patients aged 65 to 74 years, after the first dose of ondansetron 8 mg or 16 mg as a 15-minute infusion, 2 additional doses (no earlier than 4 hours) of 8 mg as a 15-minute infusion may be administered.
In patients aged 75 years and older, the dose of the first 15-minute intravenous infusion should not exceed 8 mg. After the first dose of 8 mg, 2 additional doses of 8 mg can be administered as a 15-minute infusion (no earlier than 4 hours later).
Patients with impaired renal function
No adjustment is required in the daily dose, dosing frequency, or route of administration of ondansetron.
Patients with liver dysfunction
In patients with severe and moderate liver dysfunction, the clearance of ondansetron is significantly reduced, T1/2 is significantly increased. In such patients, the daily dose of ondansetron should not exceed 8 mg.
Patients with poor sparteine/debrisoquine metabolism
In patients with slow metabolism of sparteine/debrisoquine, T1/2 of ondansetron is not changed. Therefore, when the drug is repeated, its plasma concentration will not differ from that in the general population, so no adjustment of the daily dose or dosing frequency of ondansetron is required.
Prevention and treatment of postoperative nausea and vomiting in adults and children
Adults
To prevent nausea and vomiting in the postoperative period, a single intramuscular or slow intravenous injection of Ondansetron at a dose of 4 mg is recommended during induction of anesthesia.
For the treatment of nausea and vomiting in the postoperative period, Ondansetron is administered as a single dose of 4 mg intramuscularly or slowly intravenously.
Special patient groups
Children and adolescents (ages 1 month to 18 years)
To prevent nausea and vomiting in the postoperative period in children undergoing surgery under general anesthesia, Ondansetron can be used at a dose of 0.1 mg/kg (maximum 4 mg) as a slow intravenous injection (at least 30 seconds) before, during time either after induction of anesthesia or after surgery.
Elderly patients
There is limited experience with ondansetron for the prevention and management of postoperative nausea and vomiting in elderly patients, although ondansetron is well tolerated in patients aged 65 years and older receiving chemotherapy.
Patients with impaired renal function
No adjustment is required in the daily dose, dosing frequency, or route of administration of ondansetron.
Patients with liver dysfunction
In patients with moderate to severe liver dysfunction, the clearance of ondansetron is significantly reduced and T1/2 is increased. The daily dose of ondansetron should not exceed 8 mg.
Patients with poor sparteine/debrisoquine metabolism
In patients with slow metabolism of sparteine/debrisoquine, T1/2 of ondansetron is not changed. Therefore, when ondansetron is reintroduced to such patients, its plasma concentration will not differ from that in the general population. Therefore, no adjustment of the daily dose or frequency of administration of ondansetron is required in this case.
Pharmaceutical compatibility with other solutions for intravenous administration
The following infusion solutions can be used to dilute ondansetron:
— 0.9% sodium chloride solution;
— 5% dextrose solution;
- Ringer's solution;
- 10% mannitol solution;
— 0.3% solution of potassium chloride and 0.9% solution of sodium chloride;
- 0.3% potassium chloride solution and 5% dextrose solution.
The infusion solution must be prepared immediately before use. No protection from light is required during the infusion; The diluted injection solution remains stable for at least 24 hours in natural light or normal lighting.
Compatibility with other drugs
Ondansetron can be administered as an infusion at a rate of 1 mg/hour from an infusion bag or syringe pump.
Ondansetron may be administered via the Y-port at ondansetron concentrations ranging from 16 to 160 mcg/mL (eg, 8 mg/500 mL and 8 mg/50 mL, respectively) concomitantly with the medications described below.
Cisplatin
At concentrations up to 0.48 mg/ml (eg 240 mg in 500 ml) when administered over 1 to 8 hours.
Fluorouracil
At concentrations 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/hour (500 ml/24 hours). Higher concentrations of fluorouracil may cause ondansetron to precipitate. Fluorouracil for infusion may contain up to 0.045% magnesium chloride in addition to other excipients for which compatibility has been established.
Carboplatin
Concentrations range from 0.18 mg/mL to 9.9 mg/mL (eg, 90 mg in 500 mL to 990 mg in 100 mL) when administered over 10 minutes to 1 hour.
Etoposide
Concentrations range from 0.144 mg/mL to 0.25 mg/mL (eg, 72 mg in 500 mL to 250 mg in 1 L) when administered over 30 minutes to 1 hour.
Ceftazidime
Doses ranging from 250 mg to 2 g of the drug reconstituted with water for injection according to the manufacturer's instructions for use (eg, 2.5 ml per 250 mg and 10 ml per 2 g of ceftazidime) and administered as an intravenous bolus injection over approximately 5 minutes.
Cyclophosphamide
Doses range from 100 mg to 1 g of the drug reconstituted with water for injection according to the manufacturer's instructions for use (5 ml per 100 mg of cyclophosphamide) and administered as an intravenous bolus injection over approximately 5 minutes.
Doxorubicin
Doses range from 10 mg to 100 mg of the drug reconstituted with water for injection according to the manufacturer's instructions for use (5 ml per 10 mg of doxorubicin) and administered as an intravenous bolus injection over approximately 5 minutes.
Dexamethasone
Dexamethasone sodium phosphate 20 mg may be administered as a slow intravenous injection over 2 to 5 minutes through the Y port, followed by 8 to 16 mg of ondansetron diluted in 50 to 100 mL in a compatible infusion solution over approximately 15 minutes. The compatibility of dexamethasone sodium phosphate and ondansetron was confirmed when these drugs were administered through the same administration system, resulting in expected concentrations of 32 μg/ml to 2.5 mg/ml for dexamethasone sodium phosphate and 8 μg/ml to 1 mg/ml for ondansetron.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Ondansetron is an antagonist of peripheral (in the intestines) and central (in the brain) serotonin 5-HT3 receptors. Prevents and eliminates nausea and vomiting that occurs when Serotonin during antitumor radiation and chemotherapy . Slows down intestinal motility with repeated use. It has an anti-anxiety effect, does not affect coordination of movements and does not reduce performance.
Pharmacokinetics
When administered intramuscularly, the maximum concentration in the blood is determined after 10 minutes, and when administered orally, after 1.5 hours. Eating extends the absorption time, but does not affect the maximum concentration.
Bioavailability is 60%. Ondansetron is 70-76% protein bound and partially penetrates into red blood cells . Intensively metabolized in the liver. A small amount (5%) is excreted unchanged in the urine. The half-life is 3 hours when taken orally and when administered parenterally. For older people - 5 hours.
Reviews
In general, reviews from doctors indicate the effectiveness of this drug in various dosage forms in preventing vomiting in 70–80% of patients.
An analysis of the use of Ondansetron-Altpharm in rectal suppositories containing 16 mg of active substance was carried out. It is noted that this method of administration is more preferable for patients with emetogenic syndrome. Studies have also been conducted on the effectiveness of Ondansetron lingual tablets in conditions of moderately emetogenic and highly emetogenic chemotherapy for tumors of various locations.
It was concluded that the use of Dexamethasone in combination with this drug is more effective in eliminating vomiting after chemotherapy. Ondansetron in syrup, which was used in children, is also effective in preventing vomiting in the presence of Dexamethasone, as when administered intravenously.
In pediatric surgery, postoperative vomiting is observed 2 times more often than in adult patients. This is especially common in children undergoing surgery for strabismus and adenotonsillectomies. The effectiveness of the drug has been proven after these operations, as well as in adolescents 10-16 years old, operated on for thyroid tumors. No side effects were registered.
Side effects
- Dry mouth , transient elevation of liver enzymes , constipation or diarrhea .
- Headache, seizures , movement disorders, dystonia , extrapyramidal disorders.
- Deviation of the eyes, impaired visual acuity, transient blindness.
- Chest pain, ST depression, QT prolongation, arrhythmia , hypotension , bradycardia , ventricular tachycardia .
- Bronchospasm, urticaria, laryngospasm, anaphylaxis, Quincke's edema.
- Flushing to the face, hypokalemia.
- Burning in the anus (when using a suppository), pain at the injection site.
Interaction
Be wary when prescribing Carbamazepine Monoamine Oxidase inhibitors, barbiturates, Griseofulvin , Papaverine , Rifampicin , macrolides, Erythromycin , Allopurinol , Diltiazem , Cimetidine , Omeprazole , fluoroquinolones, Metronidazole , Lovastatin , Ketoconazole , as well as with the drug mi, prolonging the QT interval.
When used together with Tramadol, there is a possibility of reducing its analgesic effect.
Concomitant use of Apomorphine hydrochloride to avoid loss of consciousness and severe hypotension.
