Pharmacological properties Ondansetron Hcl:
Ondansetron Hcl antiemetic. The mechanism of action due to the highly selective competitive blockade of central and peripheral serotonin receptors 5NT3 (receptor trigger zone, vomiting center). Suppresses the gag reflex, eliminating and preventing nausea in the application of cytotoxic chemotherapy drugs, radiation therapy in the postoperative period. Repeated application slows peristalsis and the passage of the contents of the intestines.
With a / in a dose of 0.15 mg / kg body weight for adults aged 75 years, the maximum concentration in the blood is on average about 100 ng / ml in those aged over 75 – 170 ng / ml. When i / v infusion of 32 mg over 15 minutes maximum concentration reaches 264 ng / ml. When i / m administration the maximum concentration of ondansetron in plasma (approximately 25 ng / ml) observed after 10 min after injection. Binding to plasma proteins – 70-76%.
The bulk of the administered dose (85-90%) hydroxylated in the liver involving the cytochrome P450 to the indole compounds of the cycle, and then conjugated to glucuronic and sulfuric acids. The total volume of distribution is 1.9 L / kg, elimination half-life depending on the age ranges from 3.5 to 5.5 hours, total clearance – 5.9 ml / (min · kg). The drug is excreted by the kidneys, while 5% of the administered dose is excreted unchanged. Ondansetron pharmacokinetic parameters are not changed by its repeated application.
In children, as well as in patients with liver disease decreases the total clearance in patients of advanced age increases the half-life of the drug. In patients with moderate renal insufficiency (creatinine clearance 15-60 ml / min) decreased systemic clearance and volume of distribution of ondansetron, resulting in clinically insignificant small increase in half-life of the drug. In women, the maximum concentration and bioavailability is higher and the clearance and volume of distribution is lower than in men.
Indications Ondansetron Hcl:
prevention and elimination of nausea and vomiting during cytotoxic chemotherapy (initial and repeat courses, including the use of high-dose cisplatin) and radiotherapy (irradiation of the entire surface of the body part once daily irradiation by high-or abdomen) in oncology. Prevention and elimination of nausea and vomiting in the postoperative period in general surgery, ophthalmology, etc.
USE Ondansetron Hcl:
Tablets
During cytostatic therapy the dosage is determined individually depending on the severity of vomiting reaction.
Moderate Emetogennaya chemo and radiation therapy
Adults and children over the age of 12 years inside appoint: initially 8 mg 1-2 hours before the start of antineoplastic therapy, followed by taking an additional 8 mg every 8-12 hours to prevent late or prolonged nausea and vomiting after the first 24 hours the drug should be continue to 8 mg every 12 hours Partial irradiation of the abdominal region by high-designate to 8 mg every 8 hours drug taking in the entire course of chemo-and radiotherapy, as well as 1-2 days (if needed – 3-5 days) after its completion.
High dose chemotherapy Emetogennaya
Adults and children over the age of 12 years into the prescribed 24 mg ondansetron (in conjunction with dexamethasone phosphate) for 1-2 hours before chemotherapy. For the prevention of late vomiting in the days of 8 mg 2 times a day for the entire course of chemotherapy, and 5 days after its completion.
When chemotherapy in children aged 4-12 years inside appoint: initially 4 mg 3 times daily (30 minutes before the start of the course, then – after 4 and 8 h). For the prevention of late vomiting appoint 4 mg every 8 hours for 1-2 days, then – 4 mg 2 times a day for the entire course, and 5 days after its completion.
Postoperative nausea and vomiting
Adults and children over the age of 12 years: 16 mg 1 h before anesthesia. Children under the age of 12 years, not appointed.
The maximum daily dose of ondansetron is 32 mg for patients with moderate to severe hepatic impairment – 8 mg.
Pp Injection
The drug is in the form of Valium for injection can be administered in the / m or / by a single slow injection or infusion. To prepare p-ra ondansetron infusion can use 0.9% solution of sodium chloride, 5% solution of glucose, pp Ringer. Ondansetron solution for infusion is prepared immediately before administration, but if necessary it can be stored until use no more than 24 hours at 2-8 ° C. During the infusion does not require protection from light (in normal lighting conditions).
Emetogennaya chemotherapy and radiation therapy
Adults use the p-p at a dose of 8 mg / slow immediately before chemotherapy.
High dose chemotherapy Emetogennaya
- A single dose of 8-32 mg injected into / slow immediately before chemotherapy, when administered in doses above 8 mg Ondansetron must be dissolved in 50-100 ml of 0.9% pa of sodium chloride or other compatible p-ra i / in the introduction and conduct infusion lasting at least 15 minutes;
- A dose of 8 mg / injected slowly just before the chemotherapy, then 2 times / slow at a dose of 8 mg every 2-4 hours or in / to drip at 1 mg / h for 24 h.
The choice of the dosage is determined individually depending on the severity of emetogennogo effect.
Children can be given a one-time w / a dose of 5 mg/m2 immediately before chemotherapy.
Postoperative nausea and vomiting
Adults: possible assignment of 4 mg as a slow on / in a or i / m injection during induction of anesthesia. To eliminate the development of postoperative nausea and vomiting is recommended single dose of 4 mg / m or / slow.
Children: to prevent postoperative nausea and vomiting can be prescribed at a dose of 0.1 mg / kg body weight (maximum 4 mg) / slow before, during or after induction of anesthesia. To eliminate the development of postoperative nausea and vomiting is recommended single dose of 0.1 mg / kg (maximum 4 mg) / m or / slow.
CONTRAINDICATIONS Ondansetron Hcl:
Hypersensitivity to the drug, during pregnancy (especially the I trimester) and lactation, liver failure, surgery of the abdominal cavity, the drug is not administered to children under 4 years old during chemotherapy and radiation therapy, anesthesia pill can not given to children under the age of 12 years, pp injection – up to 2 years.
SIDE EFFECTS Ondansetron Hcl:
CNS: headache, dizziness, temporary disturbance of visual acuity (with fast / in the introduction), spontaneous movement disorders, seizures, convulsions, CNS depression, paresthesia, weakness, extrapyramidal symptoms, syncope;
of the cardiovascular system: feeling the heat and flare, arrhythmia, tachycardia or bradycardia, hypotension or hypertension;
the digestive system: constipation, diarrhea, hiccups, dry mouth, transient increase in aminotransferase activity, liver failure;
allergic reactions: urticaria, bronchospasm, and in rare cases – anaphylactic reactions;
Other: cough, chest pain (anginal type), redness and burning at the injection site.
Precautions: During treatment of ondansetron breast feeding should be stopped.
For parenteral application of the drug to patients with moderate to severe hepatic impairment does not exceed the recommended dose of 8 mg / day.
In very severe vomiting reaction as a result of chemotherapy efficacy can be enhanced by a single on / in a GCS (eg 20 mg of dexamethasone sodium phosphate) before the start of chemotherapy.
With caution is prescribed for patients with a history of hypersensitivity to other selective antagonists of serotonin receptors 5NT3. With caution and under close medical supervision used the drug for the treatment of patients with signs of subacute intestinal obstruction.
INTERACTION Ondansetron Hcl:
simultaneous application of inhibitors of microsomal liver enzymes of cytochrome P450 may increase the half-life and reduce the overall clearance of the drug.
In an application with inducers of microsomal liver enzymes of cytochrome P450 (barbiturates, carbamazepine, carisoprodol, Glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin, hydantoins, rifampin, tolbutamide, etc.) may reduce clinical efficacy.
The drug infusion in the form of Valium at a concentration of ondansetron 16-160 ug / ml (8 mg/500 ml-8 mg/50 ml) can be administered through a Y-catheter in conjunction with the following medications:
- Cisplatin in concentrations up to 0.48 mg / ml within 1-8 h;
-Carboplatin at a concentration of 0,18-9,90 mg / ml for 10-60 min;
- Fluorouracil at a concentration of 0.8 mg / ml at a rate not less than 20 ml / h, while it should be noted 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, in the form of I / O bolus injection over 5 minutes;
- Cyclophosphamide at a dose of 0.1-1 g, diluted with water for injection according to the manufacturer’s recommendations, in the form of I / O bolus injection over 5 minutes;
- Doxorubicin at a dose of 10-100 mg, diluted with water for injection according to the manufacturer’s recommendations, in the form of I / O bolus injection over 5 minutes;
- Dexamethasone 20 mg / in slowly for 2-5 minutes to combine with 8-32 mg ondansetron in 50-100 ml solution of.
The drug should not be used in the same syringe or dropper to one with other drugs.
OVERDOSE Ondansetron Hcl:
If overdose is possible manifestation of side effects. Treatment – removal of the drug and symptomatic therapy aimed at maintaining vital functions. No specific antidote.
