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

Antiemetic means. Medicinal product (LFROM) for cytostatic chemotherapy and radiotherapy, an increase in the level of serotonin may be caused by the activation of vagal afferent fibers,holding 5-HT3-receptors, cause a vomitive reflex. Selectively blocks serotonin 5-HT3 receptors of neurons of the central and peripheral nervous system - the end n.vagus in the intestine and in the centers of the central nervous system (mainly the bottom of the sixth ventricle), regulating the gag reflex. 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:

After intramuscular injection, the time to reach the maximum drug concentration in the plasma (T_C_max) - 10 min. The volume of distribution after parenteral administration is 140 liters. The connection with plasma proteins is 70-76%. It is metabolized in the liver with the participation of microsomal enzymes (cytochrome CYP2D6). After parenteral administration, the half-life of the drug (T_1/2) is 3 hours. In unchanged form, less than 5% of the administered dose is excreted in the urine. The pharmacokinetic parameters of ondansetron do not change with its repeated administration. In patients with moderate renal insufficiency (creatinine clearance 15-60 ml / min) both systemic clearance and volume of distribution are reduced, resulting in a small and clinically insignificant increase T_1/2. The pharmacokinetics of ondansetron practically does not change in patients with severe renal dysfunction in chronic hemodialysis (studies were conducted in between hemodialysis sessions). In patients with severe hepatic impairment T_1/2 - 15-20 hours. T_1/2 ondansetron does not depend on the mode of administration. In elderly patients after parenteral administration of T_1/2 can increase up to 5 hours.

With the use of ondansetron in children, a decrease in the absolute values of clearance and Vd, the amount of change depends on age. Thus, in children aged 12 years the clearance is 300 ml / min, while in children at the age of 3 years-100ml / min, Vd-75 l and 17 l, respectively. Correction of the dose taking into account the patient's body weight (0.1 mg / kg, maximum to 4 mg) compensates for these changes and normalizes the system exposure of ondansetron in children.

Indications:

Prevention and elimination of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy, as well as postoperative nausea and vomiting.

Contraindications:

Hypersensitivity, pregnancy, lactation, combined use with apomorphine, congenital lengthening syndrome QT, children age up to 6 months. by indication of nausea and vomiting with chemotherapy or radiotherapy, children under 1 month of age. by indication of nausea and vomiting in the postoperative period.

Carefully:

Hypersensitivity to other 5HT3 receptor antagonists; patients with cardiac rhythm and conduction disorder, patients receiving antiarrhythmic drugs and beta-adrenoblockers; patients with significant electrolyte imbalance; patients with lengthening or risk of lengthening QTc, including patients with electrolyte imbalance, CHF, bradyarrhythmia or taking other LP, which may cause lengthening of the interval QT.

Pregnancy and lactation:

Ondansetron is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Dosing and Administration:

The choice of the dosage regimen is determined by the severity of the emetogenic effect of the antitumor therapy.

For adults, the daily dose is 8-32 mg / day, the following regimens are recommended. With moderate expression of the emetogenic effect of chemotherapy or radiotherapy - 8 mg intravenously struino slowly or intramuscularly, just before the start of therapy. With significant effect of the emetogenic effect of chemotherapy: intravenously injected slowly 8 mg immediately before the start of chemotherapy, and then intravenously struino - 8 mg every 2-4 hours; either intravenously drip continuously at a rate of 1 mg / h for 24 hours; or drip directly before the startchemotherapy in a dose of 16-32 mg, diluted in 50-100 ml of the appropriate infusion solution, for 15 minutes. The efficacy of odansetron can be increased by a single intravenous injection of glucocorticosteroid agents (eg 20 mg dexamethasone) prior to chemotherapy.

For children and adolescents (aged 6 months to 17 years), the dose of the drug is calculated from the body surface area or body weight of the child.

Calculation of the dose by the surface area of the child's body.

Ondansetron is administered immediately before chemotherapy by single

intravenous injection at a dose of 5 mg / m², the intravenous dose should not exceed 8 mg. From 2-6 days, ondansetron is administered orally. Do not exceed the dose for adults.

Calculation of the child's body weight.

Ondansetron is administered immediately before chemotherapy by a single intravenous injection at a dose of 0.15 mg / kg, the intravenous dose should not exceed 8 mg. From 2-6 days, oral administration of ondansetron begins. Do not exceed the dose for adults.

Ondansetron is well tolerated by patients older than 65 years and does not require a change in dose, frequency and route of administration.

If the kidney is damaged, correction of the usual daily dose and the frequency of administration of the drug is not required. With liver damage, the clearance of ondansetron is significantly reduced, increases T1 / 2 it is from the plasma and a dose reduction of up to 8 mg / day is required.

Prevention of postoperative nausea and vomiting: Adults are administered intramuscularly or intravenously (slowly) at a dose of 4 mg during an introductory general anesthetic. For treatment of nausea and vomiting, an intramuscular or intravenous slow administration of 4 mg of the drug is recommended. Intramuscularly in the same body region ondansetron can be administered at a dose not exceeding 4 mg.

To prevent nausea and vomiting in the postoperative period in children undergoing surgical intervention under general anesthesia, ondansetron can be administered at a dose of 0.1 mg / kg (maximum to 4 mg) in the form of a slow intravenous injection before, during or after an initial anesthesia or after surgery.

In case of kidney damage and in elderly patients, correction of the usual daily dose and frequency of administration of the drug is not required. With liver damage, the clearance of ondansetron is significantly reduced, increases T_1/2 it is from the plasma and a dose reduction of up to 8 mg / day is required.

In patients with a slow metabolism of sparteine and debrisoquine T_1/2 ondansetron is not changed. Consequently, with the repeated administration of ondansetron, its plasma concentration will not differ from that in the general population. Therefore, such patients do not need to adjust the daily dose or ondansetron frequency.

Pharmaceutical compatibility with other solutions for intravenous administration:

To dilute the injection solution, the following solutions can be used: 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 should be prepared immediately before use. If necessary, a ready-made infusion solution can be stored for up to 24 hours at a temperature of 2-8 ° C. During the infusion, protection from light is not required; The diluted injection solution retains its stability for at least 24 hours under natural light or normal light.

Side effects:

Allergic reactions: urticaria, bronchospasm, laryngospasm, angio-neurotic edema, anaphylaxis, toxic skin rash, toxic epidermal necrolysis.

From the side of the cardiovascular system: pain in the chest, in some cases with depression of the interval S-T, arrhythmias, bradycardia, lowering blood pressure, lengthening the interval Q-T, including ventricular tachycardia of the "pirouette" type.

From the nervous system: headache, dizziness, convulsions, spontaneous movement disorders, including extrapyramidal symptoms such as dystonia, oculogyric crisis, dyskinesia.

From the side of the organ of vision: transitory vision disorders, transient blindness.

From the digestive system: hiccups, constipation, an asymptomatic increase in the activity of "liver" enzymes (ALT, ACT).

Local reactions: hyperemia, pain, burning at the injection site.

Other: "tide" of blood to the skin of the face, a feeling of heat, hypokalemia, hypercreatininaemia.

Overdose:

Symptoms: increased dose-dependent adverse reactions.

Treatment: symptomatic therapy. The specific antidote is unknown.

Interaction:

Caution is required when combined with: cytochrome inducers CYP2D6 and CYP3A - barbiturates, carbamazepine, carisoprodol, glutetimide, griseofulvin, dinitrogen oxide, papaverine, phenylbutazone, phenytoin (probably, other hydantoins), rifampicin, tolbutamide; with enzyme inhibitors CYP2D6 and CYP3A - allopurinol, macrolide antibiotics, antidepressants (monoamine oxidase inhibitors), 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. Caution should be exercised when using with drugs that extend the interval QT and / or causing electrolyte imbalance. Contraindicated the use of ondansetron together with apomorphine hydrochloride, because during their joint application there were cases of severe hypotension and loss of consciousness.

With simultaneous application of ondansetron with tramadol, the analgesic effect of the latter can be reduced.

Ondansetron at a concentration of 16-160 μg / ml is pharmaceutically compatible and can be administered via Y-injector in / in the drip together with the following AC: cisplatin (at a concentration of up to 0.48 mg / ml) for 1-8 hours; fluorouracil (at concentrations up to 0.8 mg / ml at a rate of 20 ml / h - higher concentrations may cause precipitation of ondansetron); carboplatin (at a concentration of 0.18-9.9 mg / ml for 10-60 min); etoposide (in a concentration of 0.14-0.25 mg / ml for 30-60 minutes); ceftazidime (in a dose of 0.25-2 g, as an intravenous bolus injection for 5 minutes); cyclophosphamide (in a dose of 0.1-1 g, as an intravenous bolus injection for 5 min); doxorubicin (in a dose of 10-100 mg, as an intravenous bolus injection for 5 minutes); dexamethasone: possible intravenous administration of 20 mg dexamethasone sodium phosphate slowly, for 2-5 minutes. LC can be administered through a single dropper, while the concentration of dexamethasone sodium phosphate in the solution can range from 32 to 2500 μg / ml, ondansetron - from 8 to 100 μg / ml.

Special instructions:

Patients who had previously had allergic reactions to other selective 5-HT3 receptor blockers have an increased risk of developing them against ondansetron. In patients with an increased risk of lengthening the interval QT it is necessary to correct hypokalemia and hypomagnesemia. Ondansetron can slow the motility of the large intestine, in connection with which its appointment to patients with signs of intestinal obstruction requires special observation.

Effect on the ability to drive transp. cf. and fur:The drug does not adversely affect the ability to drive vehicles and work with mechanisms.

Form release / dosage:Solution for intravenous and intramuscular injection 2 mg / ml.

Packaging:

2 ml or 4 ml in ampoules of dark glass or colorless neutral glass-

5 ampoules are placed in a contour cell pack. 1 or 2 contour squares are placed in a pack of cardboard for consumer containers.

5, 10 ampoules are placed in a pack of cardboard with baffles or lattices, or a cardboard separator. 10 ampoules are placed in a box.

In each pack or box, put the instructions for use and the ampoule scaler. When using ampoules with an incision, a ring of fracture or a break point, the ampoule scaper is not inserted.

Storage conditions:

In a place protected from light and inaccessible to children at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002624

Date of registration:17.09.2014

Expiration Date:17.09.2019

The owner of the registration certificate:BIOCHEMIST, OJSC BIOCHEMIST, OJSC Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspBIOCHEMICAL JSC BIOCHEMICAL JSC Russia

Information update date: & nbsp07.06.2017

Illustrated instructions

Instructions

Ondansetron (Ondansetron)