Ondansetron-LENS - instructions for use, doses, side effects, contraindications

Ondansetron is a selective receptor antagonist 5-HT₃(serotonin). Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in the level of serotonin, which by activation of vagal afferent fibers containing receptors 5-HT₃, causes a vomitive reflex. Selectively blocks serotonin 5-HT₃receptors of neurons of the central and peripheral nervous system, endings n.vagus in the intestine and in the centers of the central nervous system (mainly the bottom of the IV ventricle), which regulate the exercise of vomitive reflexes. Does not disrupt the coordination of movements, does not cause sedation and reduced efficiency. Does not change the concentration of prolactin in the plasma.

Pharmacokinetics:

After intramuscular injection, the time to reach the maximum plasma concentration (T_C_max)-10 min. Binding to plasma proteins is 70-76%. The volume of distribution is 140 liters. After parenteral administration, the elimination half-life (T_1/2) is 3 hours. The absence of isoenzyme CYP2D6 (debrisohin polymorphism) does not affect the pharmacokinetics of ondansetron.

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 impairment of liver function, the systemic clearance of ondansetron drastically decreases, resulting in a longer half-life of 15-20 hours. T_1/2 ondansetron does not depend on the mode of administration.

In elderly patients after oral administration or parenteral administration T_1/2 can increase up to 5 hours.

Indications:

- Prevention and elimination of nausea and vomiting caused by cytostatic chemotherapy or radiotherapy;

- prevention and elimination of nausea and vomiting in the postoperative period.

Contraindications:

- Hypersensitivity to ondansetron or other components of the drug;

- Pregnancy and the period of breastfeeding; children's age until 2-years old.

Carefully:

Use with caution in patients with cardiac rhythm and conduction abnormalities, patients receiving antiarrhythmics and beta-blockers and patients with significant electrolyte disorders (single cases of transient ECG changes were recorded, including interval lengthening QT).

Pregnancy and lactation:Due to the lack of clinical data on safety, taking ondansetron during pregnancy and during breastfeeding is contraindicated. If necessary, use during lactation should stop breastfeeding.

Dosing and Administration:

Cytostatic therapy

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, the following regimens are recommended:

With moderately-emetogenic chemotherapy or radiotherapy:

8 mg intravenously struino slowly or intramuscularly, immediately before the start of therapy;

With highly emeticogenic chemotherapy:

- 8 mg intravenously slowly before the start of chemotherapy, then two more intravenous injections of 8 mg, each of which is carried out in 2-4 hours

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

- 16-32 mg, diluted in 50-100 ml of the appropriate infusion solution, as a 15-minute infusion, immediately before the start of chemotherapy. The efficacy of ondansetron can be increased by a single intravenous injection of glucocorticosteroids (for example, 20 mg dexamethasone) prior to chemotherapy.

To prevent delayed emesis that occurs after the first 24 hours from initiation of chemotherapy or radiotherapy - both with the use of highly emetic therapy, and with moderately emetic therapy - it is recommended to continue using ondansetron inside within 5 days.

Children over 2 years old the drug is given in a dose of 5 mg / m² the surface of the body intravenously, immediately before the start of chemotherapy, followed by ingestion of 4 mg after 12 hours; treatment is recommended to continue at a dose of 4 mg 2 times a day inside for 5 days.

Prevention of postoperative nausea and vomiting

Adults inject a single dose of 4 mg intramuscularly or intravenously slowly at the onset of anesthesia.

For relief of nausea and vomiting it is recommended intramuscular or slow intravenous injection of 4 mg of the drug.

Intramuscularly in the same body region ondansetron can be administered at a dose not exceeding 4 mg!

Children to prevent postoperative nausea and vomiting ondansetron is used exclusively parenterally in a single dose 0,1 mg / kg (max. 4 mg) as a slow intravenous injection before or after anesthesia.

To treat the development of postoperative nausea and vomiting in children, slow intravenous administration of a single dose of the drug 0,1 mg / kg (up to max. 4 mg).

With regard to the prevention and treatment of postoperative nausea and vomiting in children under the age of 2 years of sufficient experience there.

Elderly patients

Dosage adjustments are not required.

Patients with impaired renal function

Change the usual daily dose and the frequency of administration of the drug is not required.

Patients with impaired hepatic function

With moderate or severe impairment of liver function, the clearance of ondansetron is significantly reduced, while the half-life of plasma is increased from plasma, so it is not recommended for such patients to prescribe more 8 mg ondansetron per day.

To dilute the ondansetron injection solution, the following solutions can be used:

0.9% solution of sodium chloride,

5% dextrose solution,

Ringer's solution,

0.3% potassium chloride solution and 0.9% sodium chloride solution,

0.3% potassium chloride solution and 5% dextrose solution.

Side effects:

Side effects are classified according to organ systems.

The immune system: reactions of immediate hypersensitivity (including severe, up to anaphylaxis)

Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema.

Nervous system: headache; Extrapyramidal reactions, such as oculogic crisis, dystonic reactions without persistent clinical consequences, convulsions; dizziness during the period of rapid intravenous administration of the drug, dyskinesia.

Visual disturbances: transient visual disturbances (blurred vision), mainly during the period of intravenous administration; blindness, mainly during intravenous use. In most cases of blindness it lasts for 20 minutes.

From the side of the cardiovascular system: sensation of heat or "tide" of blood; arrhythmias, chest pain (with segment depression ST or without it), bradycardia, arterial hypotension, lengthening of the interval Q-T.

From the respiratory system: hiccups.

From the digestive system: constipation; in isolated cases - an asymptomatic increase in hepatic samples.

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

Overdose:

Symptoms: the development of side effects in a more pronounced form. In cases of suspected overdose, symptomatic therapy is indicated. The specific antidote is unknown. In case of an overdose of ondansetron, the use of ipecacuanas is not recommended, as it is unlikely that this drug will be effective during the antiemetic activity of ondansetron.

Interaction:

As ondansetron metabolized by the enzyme system (isoenzyme cytochrome P450) of the liver,Care must be taken when using together:

- with inductors of isoenzymes P450 (CYP2D6 and CYP3A) - barbiturates, carbamazepine, carisoprodol, glutetimide, griseofulvin, dinitrogen oxide, papaverine, phenylbutazone, phenytoin (probably other hydantoins), rifampicin, tolbutamide;

- with inhibitors of isoenzymes P450 (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.

Ondansetron at a concentration of 16-160 μg / ml is pharmaceutically compatible and can be administered via Y-injector intravenously drip with the following drugs:

- cisplastin (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 ondansetron precipitation);

- 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 0.25-2.0 g, as an intravenous bolus injection for 5 minutes);

- cyclophosphamide (in a dose of 0,1-1,0 g, as an intravenous bolus injection for 5 minutes);

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

- dexamethasone: possible intravenous administration 20 mg dexamethasone slowly, for 2-5 minutes. The drug can be administered through a single dropper, while in a solution the concentrations of dexamethasone can range from 32 μg to 2.5 mg / ml, ondansetron - from 8 μg / ml up to 0,1 mg / ml.

- when used simultaneously with powerful isoenzyme inducers CYP3A may decrease the concentration of ondansetron in the blood

- With tramadol: there have been reports of a decrease in the analgesic effect of tramadol when combined with ondansetron.

Special instructions:

Patients who had previously had allergic reactions to other selective blockers 5-HT₃-receptors, have an increased risk of their development against the background of ondansetron. Ondansetron can slow the motility of the colon, in connection with which its appointment to patients with signs of intestinal obstruction requires regular monitoring.

The infusion solution should be prepared immediately before use. If necessary, the ready-made infusion solution can be stored for up to 24 hours at a temperature of 2-8 ° C at normal illumination.

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.

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

Studies to study the effect of the drug on the ability to drive and work with mechanisms were not conducted. Given the safety profile, when taking ondansetron should be careful when driving a car and working with mechanisms.

Form release / dosage:

Solution for intravenous and intramuscular injection, 2 mg / ml.

Packaging:

2 or 4 ml in bottles of glass.

1 a bottle together with instructions for use in a pack of cardboard.

For 5 or 10 bottles together with instructions for use in a pack with partitions or special cardboard sockets.

For 50, 85 or 100 bottles with an equal number of instructions for use in a cardboard box (for hospitals).

Storage conditions:At a temperature not exceeding 30FROM.

Keep out of the reach of children.

Shelf life:3 years.

Terms of leave from pharmacies:On prescription

Registration number:P N001877 / 01

Date of registration:19.09.2008 / 04.08.2016

Expiration Date:Unlimited

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp07.06.2017

Illustrated instructions

Instructions

Ondansetron-LENS® (Ondansetron-LANS®)