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

Antiemetic means. Ondansetron prevents and eliminates nausea and vomiting postoperative and induced by cytostatic chemotherapy (including cisplatin-containing) and radiotherapy.

Selectively blocking serotonin 5-HT₃-receptors of central neurons (vomiting center) and peripheral nervous system (afferent fibers of the vagus nerve in the intestine), thereby impeding the realization of the effect serotonin, the release of which promotes cytostatic therapy, ondansetron prevents the development of a vomitive reflex.

Does not violate the coordination of movements, does not cause sedation and reduced efficiency. Does not change the concentration of prolactin in the plasma.

Pharmacokinetics:

The time to reach the maximum concentration (T_mOh) after intramuscular injection - 10 min. The volume of distribution is about 140 liters (Vd: adults 2.2 - 2.5 l / kg, children - 1.7 - 3.7 l / kg). The connection with plasma proteins is 70-76%. The elimination half-life for intravenous and intramuscular injection does not differ. Half-life (T_1/2) is 3 hours and does not differ with single and course admission; in elderly patients reaches 5 hours Metabolised in the liver with the participation of microsomal enzymes CYP1A2, CYP2D6 (predominantly) and CYP3A4. Does not affect the activity of enzymes of the P-450 system. Absence of CYP2D6 (polymorphism debrisohina) does not affect the pharmacokinetics of ondansetron. Unchanged in the urine is displayed less 5% of the administered dose. Does not possess cumulative properties.

The pharmacokinetic parameters of ondansetron do not change with its repeated administration.

From the age of 15, pharmacokinetics does not differ from that in adults. Children 4-12 years in comparison with adults, more distribution; accelerated breeding - T_1/2 is 2.4 hours.

In women, compared with men, the maximum concentration and bioavailability is higher, the clearance of the drug is slower, the volume of distribution is less. In patients with moderate renal failure (creatinine clearance, 15-60 ml / min) are reduced as systemic clearance, and V_d ondansetron; resulting in a small and clinically insignificant increase in its T_1/2 (up to 5.4 hours). The pharmacokinetics of ondansetron practically does not change in patients with severe renal dysfunction, which are on chronic hemodialysis.

In patients with severe impairment of liver function, the systemic clearance of ondansetron drastically decreases, as a result of which T_1/2 increases to 15 - 20 hours.

Indications:

Prevention and management of nausea and vomiting caused by cytostatic chemotherapy and radiotherapy.

Prevention and management of postoperative nausea and vomiting.

Contraindications:

Hypersensitivity to ondansetron and / or any of the components of the drug; pregnancy, lactation, children under 2 years of age (safety and efficacy not proven).

Carefully:Syndrome of elongated QT-Interval (congenital and acquired forms).

Pregnancy and lactation:

Contraindicated.

Dosing and Administration:

Nausea and vomiting induced by cytostatic chemotherapy or radiotherapy.

The choice of dosage regimen is determined by the emetogenicity of antitumor therapy.

Adults: daily dose is 8-32 mg. The following modes are recommended.

With moderately emetogenic chemotherapy or radiotherapy: 8 mg intravenously struino slowly or intramuscularly, just before chemotherapy or radiotherapy.

With highly emeticogenic chemotherapy:

- 8 mg intravenously slowly, immediately before the start of chemotherapy, followed by the appointment of two more injections of the drug intravenously struino slowly - 8 mg every 2 to 4 hours;

- 24 mg, continuous 24-hour infusion of the drug at a rate of 1 mg / h;

-16-32 mg, diluted in 50 - 100 ml of the appropriate infusion solution, a 15-minute infusion immediately before the start of chemotherapy.

Further, to prevent delayed nausea and vomiting (with both moderate and high emetogenicity), therapy should be continued with an oral dose (8 mg twice daily for 5 days).

Combined with dexamethasone therapy - a single intravenous injection of 20 mg dexamethasone 45 minutes prior to chemotherapy (potentiation of antiemetic effect, complete control of both acute and delayed emesis).

Children over 2 years: intravenously at a dose of 5 mg / m² body surface immediately before chemotherapy followed by oral administration at a dose of 4 mg after 12 hours.After the end of the course of chemotherapy, it is necessary to continue taking ondansetron in a dose of 4 mg twice a day for 5 days.

Prevention of postoperative nausea and vomiting:

Adults - In the period of the initial general anesthesia, intramuscularly or intravenously (slowly) at a dose of 4 mg.

For relief of nausea and vomiting, 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.

Children over 2 years old to prevent postoperative nausea and vomiting ondansetron is used exclusively parenterally, in a single dose of 0.1 mg / kg (but not more than 4 mg) slowly intravenously before or after anesthesia. To treat the development of postoperative nausea and vomiting in children, a slow single intravenous injection of the drug at a dose of 0.1 mg / kg (but not more than 4 mg) is recommended.

Patients of advanced age. Dosage adjustments are not required.

Patients with renal insufficiency. Dosage adjustments are not required.

Patients with impaired hepatic function. Daily dose ondansetron should not exceed 8 mg per day.

Patients with a slow metabolism of sparteine / debrisoquine: Corrections a daily dose or frequency of admission of ondansetron is not required.

To prepare the infusion solution, 0.9% sodium chloride solution, 5% dextrose solution, 10% mannitol solution, Ringer's solution can be used.

The infusion solution is prepared immediately before use. If necessary, it can be stored for 24 hours at a temperature of 2-8 °.

Side effects:

From the central nervous system: headache, dizziness, spontaneous movement disorders and convulsions. Extrapyramidal disorders, such as the oculogic crisis / dystonic reactions, are rare (less than 1%), usually short-lived and are the result of accelerated intravenous administration of ondansetron.

From the side of the organs of sight: transient blurred vision and transient blindness, usually caused by accelerated (less than 15 minutes) intravenous administration of the drug.

From the gastrointestinal tract: constipation, diarrhea, hiccough, dry mouth, sometimes a transient asymptomatic increase in hepatic transaminase activity.

From the side of the cardiovascular system: bradycardia, tachycardia, hypotension, palpitation, chest pain, arrhythmias, fainting. Electrocardiographic changes consist in lengthening QT-Interval, depression STsegment. Allergic reactions: urticaria, bronchospasm, laryngospasm, anaphylaxis, angioedema.

Local reactions: pain, burning and redness at the injection site.

Other: fatigue, weakness / malaise, fever, chills; paresthesia, itching hypokalemia, hypercreatininaemia, "tide" of blood to the skin of the face, a feeling of heat.

Overdose:

Symptoms are similar to the side effects of the drug.

In cases of suspected overdose, symptomatic and maintenance therapy. The specific antidote is unknown.

Interaction:

Medicinal and vegetative agents, inducing enzyme CYP3A4, It is permissible to combine with ondansetron only under the supervision of a physician. It is known that St. John's Wort helps reduce the concentration of ondansetron. Inductors of the enzyme CYP3A4 (phenytoin, carbamazepine and rifampicin) and inductors CYP2D6 and CYP1A2 (barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin (probably other hydantoins), rifampicin, tolbutamide) reduce the concentration of ondansetron in the blood and accelerate its elimination. Inhibitors CYP2D6 and CYP1A2 (macrolide antibiotics, antidepressants-MAO inhibitors, chloramphenicol, cimetidine, estrogen-containing oral contraceptives, diltiazem, disulfiram, valproic acid and its salts, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil) lead to a slowing of biotransformation and excretion.

Ondansetron does not interact with alcohol, temazepam, furosemide, tramadol and propofol (diprivanom).

Compatible with ondansetron preparations: all cytostatic drugs; antibacterial (cefazolin, cefotaxime, ceftazidime, cefuroxime, gentamicin, amikacin, clindamycin, thienes, ertapenem, gatifloxacin, doxycycline, vancomycin, timentin), glucocorticosteroid (dexamethasone, hydrocortisone), mannitol, magnesium sulfate, potassium chloride, sodium acetate, cimetidine, famotidine, ranitidine, droperidol, haloperidol, morphine, remifentanil, chlorpromazine, metoclopramide, diphenhydramine, dopamine, fluconazole, heparin, zidovudine.

Incompatible preparations: acyclovir, allopurinol, aminophylline, amphotericin B, ampicillin, incl. protected, cefepime, cefoperazone, furosemide, ganciclovir, lorazepam, methylprednisolone, piperacillin, sodium hydrogen carbonate. After the risk / benefit evaluation: fluorouracil, meropenem.

Pharmaceutical compatibility. Pharmaceutically ondansetron in a concentration of 16-160 μg / ml is compatible and can be administered through Y-shaped catheter intravenously drip along with the following drugs: cisplatin (in a concentration of up to 0.48 mg / ml) for 1 to 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 (in 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 (at a dose of 0.25 - 2 g, as an intravenous bolus injection for 5 min);

cyclophosphamide (in a dose of 0.1 - 1 g, as an intravenous bolus injection for 5 minutes);

doxorubicin (in a dose of 10-100 mg, as an intravenous bolus injection for 5 minutes);

dexamethasone: possibly intravenous administration of 20 mg dexamethasone sodium phosphate slowly, for 2-5 minutes. Drugs 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 previously had allergic reactions to other selective blockers 5-HT₃-receptors, have an increased risk of their development with ondansetron. 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.

In special observation, patients with the syndrome of the extended QT-interval (congenital and acquired forms), as well as patients, genetically predisposed to this pathology (family history).

Intravenous ondansetron should be administered slowly, for at least 15 minutes.

Children to prevent and eliminate postoperative nausea and vomiting ondansetron is administered exclusively parenterally.

Effect on the ability to drive transp. cf. and fur:

During the use of the drug, patients should be very careful to drive and engage in other potentially dangerous species activities that require a high rate of psychomotor reactions, due to possible side effects from the CNS, such as dizziness and blurred vision.

Form release / dosage:Solution for intravenous and intramuscular injection. Ampoules of 2 (4 mg / 2 ml) or 4 (8 mg / 4 ml) ml.

Packaging:

Ampoules of 2 (4 mg / 2 ml) or 4 (8 mg / 4 ml) ml. The ampoule has a break point. 4 ampoules together with instructions for use in a pack of cardboard with partitions or a cardboard insert.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date stated on the package

Terms of leave from pharmacies:On prescription

Registration number:PL-000577

Date of registration:26.08.2011

Expiration Date:26.08.2016

The owner of the registration certificate:MAKIZ-PHARMA, LLC MAKIZ-PHARMA, LLC Russia

Manufacturer: & nbsp

MAKIZ-PHARMA, LLC Russia

Representation: & nbspMAKIZ-PHARMA, LLCMAKIZ-PHARMA, LLCRussia

Information update date: & nbsp07.06.2017

Illustrated instructions

Instructions

Ondansetron (Ondansetron)