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

In 1 ml of solution contains: active substance ondansetron hydrochloride dihydrate (in terms of ondansetron) 2.50 (2.00) mg; Excipients: citric acid monohydrate 0.50 mg, sodium citrate dihydrate 0.33 mg, sodium chloride 8.30 mg, water for injection up to 1 ml, sodium citrate dihydrate q.s., hydrochloric acid q.s.

Description:clear colorless solution

Pharmacotherapeutic group:antiemetics, serotonin receptor antagonist

ATX: & nbsp

A.04.A.A.01 Ondansetron

Pharmacodynamics:

Ondansetron is a selective antagonist of serotonin 5-hydroxytryptamine type 3 receptors (5-HTs). Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in the concentration of serotonin, which by activation of vagal afferent fibers containing receptors 5-HTs, causes a vomitive reflex. Ondansetron inhibits the appearance of a vomiting reflex by blockade of receptors 5-HTZ at the level of neurons of both the central and peripheral nervous system. Does not disrupt the coordination of movements, does not cause sedation and reduced efficiency.

Ondansetron does not affect the concentration of prolactin in the serum.

Pharmacokinetics:

With intramuscular (IM) administration, the maximum concentration is reached 10 minutes after the injection. The distribution of ondansetron is the same for

intramuscular and intravenous administration. Volume of distribution (Vd) when the equilibrium state is reached, 140 liters, binding to plasma proteins - 70-76%. From the systemic blood flow ondansetron Eliminated mainly as a result of metabolism in the liver with the participation of several enzyme systems. With urine in unchanged form, less 5% preparation. Absence of isoenzyme CYP2D6 (polymorphism of debrisoquine) does not affect the pharmacokinetics of ondansetron. Half-life (T1 / 2) for parenteral administration, as well as after ingestion, is about 3 hours. Pharmacokinetic parameters of ondansetron do not change when it is used multiple times.

Pharmacokinetics in special clinical cases. Have patients with a creatinine clearance of 15-60 ml / min were reduced both for systemic clearance and Vd ondansetron, resulting in a small and clinically insignificant increase in T1 / 2 (up to 5.4 h).The pharmacokinetics of ondansetron practically does not change in patients with severe impairment of renal function on hemodialysis.

In patients with severe impairment of liver function, the systemic clearance of ondansetron drastically decreases, and as a result, it increases T1 / 2 (up to 15-32 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. So, in children aged 12

years, the clearance is 300 ml / min, and in children aged 3 years - 100 ml / 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 management of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy.

- Prevention and relief of nausea and vomiting in the postoperative period.

Contraindications:

Hypersensitivity to ondansetron, other selective antagonists of serotonin 5HTs-receptors and other components of the drug; pregnancy and the period of breastfeeding; children's age to 2 years (not enough data on efficiency and safety).

Carefully:

If cardiac rhythm and conduction are disturbed, antiarrhythmic drugs or beta-blockers are applied simultaneously, electrolyte balance, liver failure, intestinal obstruction (including suspicion) are disturbed.

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, as a rule, is 8-32 mg, the following regimens are recommended:

with moderate emetogenic chemotherapy or radiotherapy: 8 mg intravenously (iv) slowly or in / m, immediately before the start of therapy; with highly emetogenic chemotherapy:

- 8 mg IV slowly before the start of chemotherapy, and then two in / in jet injections of 8 mg, each of which is carried out at intervals of 2-4 hours;

- continuous 24-hour IV infusion 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, in the form of a 15-minute IV infusion, immediately before the start of chemotherapy.

The efficacy of ondansetron can be increased by a single intravenous glucocorticoid (eg, 20 mg dexamethasone) prior to chemotherapy.

To prevent delayed emesis that occurs 24 hours after the initiation of chemotherapy or radiotherapy, it is recommended to continue the use of the drug inside 8 mg twice a day for 5 days.

Children over 2 years old is prescribed in a dose of 5 mg / m² surface of the body in / in immediately before the start of chemotherapy followed by oral administration at a dose of 4 mg after 12 hours;

after the end of chemotherapy, it is recommended to continue treatment at 4 mg twice daily for 5 days.

Prevention of postoperative nausea and vomiting

Adults a single dose of 4 mg/ m or in / in slowly, at the beginning of anesthesia.

For relief of nausea and vomiting it is recommended in / m or slow iv injection of 4 mg of the drug.

V / m in the same body area 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 (maximum to 4 mg) as a slow intravenous injection immediately before, during or after anesthesia.

To treat the development of postoperative nausea and vomiting in children, a slow administration of a single dose of 0.1 mg / kg (maximum 4 mg) is recommended.

Elderly patients and patients with kidney damage changing the dosing regimen is not required.

With liver damage significantly decreases the clearance of ondansetron, and its T1 / 2 from the plasma, so do not exceed the daily dose of 8 mg per day. The following solutions can be used to dilute the injection solution.

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:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

Allergic reactions: rarely - urticaria, bronchospasm, laryngospasm,

angioedema, immediate-type hypersensitivity reactions, including anaphylaxis.

From the nervous system: very often - headache; infrequently - convulsions, spontaneous movement disorders, including extrapyramidal disorders (dystonic reactions, oculogic crisis, dyskinesia),which are reversible and do not lead to persistent clinical consequences; rarely - dizziness due to rapid IV injection.

From the side of the organ of vision: rarely - a temporary decrease in visual acuity; very rarely - temporary blindness, mainly after IV introduction.

From the cardiovascular system: infrequently - pain in the chest, in some cases accompanied by depression of the segment S-T arrhythmia, bradycardia, decrease

blood pressure (BP); rarely - transient changes in the electrocardiogram (ECG), including lengthening of the interval QT, preferably with iv introduction.

From the digestive system: often constipation; infrequently - hiccough, dryness of the oral mucosa, diarrhea, transient increase in the activity of "liver" transaminases.

Other: often - a feeling of heat, "hot flashes", irritation, flushing, pain, burning at the injection site; rarely - hypokalemia, hypercreatininaemia.

Overdose:

Symptoms: visual impairment (amaurosis for 2-3 min), constipation, decreased blood pressure and vasovagal syncope with transient atrioventricular blockade of degree II. All symptoms are completely reversible.

Treatment: conduct symptomatic and maintenance therapy, a specific antidote is not known.

Interaction:

No data that ondansetron induces or inhibits the metabolism of other drugs, often prescribed in combination with it.

According to special studies, it has been established that ondansetron does not interact with ethanol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental sodium and propofol.

Ondansetron is metabolized by several isoenzymes of the cytochrome P450 system (CYP3A4, CYP2D6 and CYP1A2). In connection with the variety of isoenzymes that are able to metabolize ondansetron, inhibition of isoenzymes or a decrease in the activity of one of the isoenzymes (for example, in genetic isoenzyme deficiency CYP2D6) is usually compensated by other isoenzymes, as a result of which changes in the total clearance of ondansetron are either absent or insignificant and practically do not require dose adjustment.

In patients taking potent inducers of isoenzyme CYP3A4 (phenytoin, carbamazepine and rifampicin), the concentration of ondansetron in the blood can decrease.

Data from special studies indicate that ondansetron can reduce the anesthetic effect of tramadol.

Use of ondansetron together with drugs that extend the interval QT, can lead to an additional lengthening of this interval.

The simultaneous use of ondansetron with drugs that have cardiotoxic properties (anthracyclines) may increase the risk of arrhythmias.

Ondansetron at a concentration of 16-160 μg / ml is pharmaceutically compatible with the following drugs, which can be administered via Y-shaped injector: cisplatin (in a concentration of up to 0.48 mg / ml) for 1-8 hours;

fluorouracil (at a concentration of up to 0.8 mg / ml at a rate of 20 ml / h - higher concentrations may precipitate 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 (in a dose of 0.25-2.0 g, as an IV bolus injection for 5 minutes); cyclophosphamide (in a dose of 0.1-1.0 g, as an IV bolus injection for 5 minutes); doxorubicin (in a dose of 10-100 mg, as an IV bolus injection for 5 minutes); dexamethasone: possible iv injection of 20 mg dexamethasone slowly, for 2-5 minutes.Drugs can be administered through a single dropper, while in a solution the concentrations of dexamethasone sodium phosphate can range from 32 μg to 2.5 mg / ml, ondansetron - from 8 μg to 1 mg / ml.

Special instructions:

Have patients who had previously used other selective antagonists 5HT3 - receptors, there were reactions of hypersensitivity, with the application of ondansetron, similar reactions can also develop.

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 25 ° C or for 7 days at 5 ° C (in the refrigerator).

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 artificial light.

With the use of ondansetron, mainly with intravenous administration, there may be changes in the ECG of a transient nature, including lengthening of the interval QT, so you should use caution ondansetron in patients with cardiac dysfunction
rhythm and conduction, in patients taking antiarrhythmic drugs or beta-blockers, in patients with electrolyte imbalance.

Ondansetron should not be given to children with a body surface area of less than 0.6 m².

As ondansetron slows the bowel motility, patients with symptoms of intestinal obstruction require regular monitoring of the doctor.

Ondansetron can not be used to prevent and treat postoperative nausea and vomiting in children after surgery on the abdominal organs.

In patients with adeno- or tonsillectomy, the use of ondansetron as a prophylaxis for nausea and vomiting can mask latent bleeding.

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

Care should be taken when using Ondansetron-Teva because of the possible development of adverse reactions (dizziness, temporary loss of visual acuity, temporary blindness), which can adversely affect the ability to drive vehicles and perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions .

Form release / dosage:

Solution for intravenous and intramuscular injection 2 mg / ml.

Packaging:

For 2 ml or 4 ml of the drug in a vial of clear, colorless glass (type I).

To 5 or 10 ampoule into an open contour cell package. One open contour pack together with the instruction for use is put in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000897

Date of registration:14.09.2011

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp19.06.2013

Illustrated instructions

Instructions

Ondansetron-Teva (Ondansetron-Teva)