Expiration date: 08/2026

The composition and form of issue:

Solution for intravenous and intramuscular injection, 1 ml contains:

ondansetron hydrochloride dihydrate 2.5 mg

(in terms of ondansetron 2 mg)

excipients: citric acid monohydrate sodium citrate sodium chloride water for injections

in ampoules of 2 or 4 ml, in a contour plastic box (pallet) with 5 ampoules in a pack a cardboard 1 package (pallet).

Lozenges. 1 tablet contains:

ondansetron 4 or 8 mg

excipients: gelatin mannitol aspartame sodium methylhydroxybenzoate sodium propylhydroxybenzoate strawberry flavour purified water 

blistere in 10 PCs. in cardboard pack 1 blister.

Syrup. 5 ml contains:

ondansetron hydrochloride dihydrate 5 mg

(equivalent to 4 mg of ondansetron) 

excipients: citric acid anhydrous sodium citrate dihydrate sodium benzoate sorbitol solution, strawberry flavor purified water 

in vials of 50 ml, complete with measuring spoon in the box 1 set.

Suppositories for rectal application. 1 suppositorie contains:

ondansetron 16 mg

excipients: witepsol S58 

the strip 1 supp. in the paper cartons 1 or 2 strip.

Description pharmaceutical form:

The solution for the on/in and/m introduction: clear, colorless liquid, practically free from foreign inclusions.

Lozenges: round, white, convex on one side and flat on the other.

Syrup: transparent liquid from colorless to light yellow in color with a characteristic smell of strawberries.

Suppositories: white, smooth, homogeneous, having the shape of a cylinder with a pointed end.

Pharmacokinetics:

Ondansetron completely absorbed in the gastrointestinal tract after ingestion and undergoes first pass metabolism through the liver. Cmax in plasma is approximately 1.5 h after administration. Bioavailability slightly increases at simultaneous food intake, but changes in the of antacids.

Distribution of ondansetron are equally in oral administration, in/m and/in the introduction T1/2 approximately 3 h, in elderly patients may reach 5 h, and in severe renal failure — 15-20 h. the Volume of distribution at equilibrium of the concentration is about 140 L. plasma protein Binding is 70 to 76%. After a rectal ondansetron is determined in plasma after 15-60 min, the Concentration of active substance increases linearly Cmax is reached after about 6 h and is 20-30 ng/ml. The decline in plasma concentration occurs at a slower rate than after ingestion (due to continued absorption). T1/2 is 6 h. the Absolute bioavailability of rectal administration is 60%.

Systemic blood flow it is eliminated mainly as a result of metabolism in the liver, which occurs with the participation of several enzyme systems. The absence of the enzyme CYP2D6 (polymorphism spartein-debricking type) does not affect the pharmacokinetics of ondansetron. In an unmodified form with urine output less than 5% of the administered dose.

At doses above 8 mg content in the blood increases disproportionately, since at high doses may decrease inside a metabolism at the first passage through the liver.

Pharmacokinetic parameters of ondansetron do not change when re-admission.

In patients with moderate renal insufficiency (Cl creatinine — 15-60 ml/min) reduced systemic clearance and volume of distribution of ondansetron, resulting in a small and clinically insignificant increase its T1/2 (up to 5.4 h). Ondansetron pharmacokinetics remains virtually unchanged in patients with severe impairment of renal function, which is on chronic hemodialysis. In patients with severe hepatic impairment drastically reduced systemic clearance of ondansetron, resulting in increases its T1/2 (up to 15-32 h) and an oral bioavailability approaching 100% due to the reduction of first-pass metabolism.

Special groups of patients

Sex

The pharmacokinetics of ondansetron depends on the sex of the patients. In women, the observed lower systemic clearance and volume of distribution (adjusted for body mass) than males.

Children and adolescents (aged 1 month to 17 years)

In one clinical trial, children aged 1 to 24 months (51 patients) received ondansetron in a dose of 0.1 mg/kg or 0.2 mg/kg prior to surgery. Patients aged 1 to 4 months Cl was approximately 30% less than in patients aged 5 to 24 months but comparable to the rate in patients aged 3 to 12 years (with correction indicators depending on body weight). T1/2 in the group of patients aged 1-4 months on average to 6.7 h in the age groups 5-24 months and 3-12 years, 2.9 hours Patients aged 1 to 4 months dose adjustment is not required because it applies a single on/in the introduction of ondansetron for treatment of postoperative nausea and vomiting in these patients. The differences of pharmacokinetic parameters partially explains the higher volume of distribution in patients aged 1 to 4 months.

In a study in children aged 3-12 years (21 patients), undergoing routine surgical procedures under General anaesthesia, the absolute values of Cl and volume of distribution of ondansetron following a single I/V administration at a dose of 2 mg (3 to 7 years) or 4 mg (8 to 12 years old) were reduced compared to values in adults. Both parameters increased linearly depending on the body weight, in patients aged 12 years these values were close to values in adults. The correction values of clearance and volume of distribution depending on body mass, these parameters were close in different age groups. Dose calculated based on body weight (0.1 mg/kg, maximum 4 mg) compensates for these changes and systemic exposure of ondansetron in children.

Was was conducted a population pharmacokinetic analysis of 74 patients aged 6 to 48 months who are/were administered ondansetron in the dose of 0.15 mg/kg every 4 h number 3 doses for the relief of nausea and vomiting caused by chemotherapy, and 41 patients aged 1 to 24 months after surgery, which was administered ondansetron in a single dose of 0.1 or 0.2 mg/kg. Based on the pharmacokinetic parameters in this group are for patients aged 1 to 48 months the introduction of ondansetron in/in the dose 0.15 mg/kg every 4 h number 3 doses should lead to achieve systemic exposure comparable to that observed when using the drug in the same doses in children aged 5 to 24 months with surgical intervention and also in previous studies in children with cancer (aged 4 to 18 years) and at surgery (age 3 to 12 years).

Elderly patients

The study showed a weak, clinically insignificant, age-dependent increase in T1/2 of ondansetron.

Patients with impaired renal function

In patients with moderate renal impairment (Cl creatinine clearance 15-60 ml/min) with the/in the introduction of ondansetron reduced systemic clearance and volume of distribution of ondansetron, resulting in a small and clinically insignificant increase in T1/2 (up to 5.4 h). The pharmacokinetics of ondansetron at/in the introduction remained almost unchanged in patients with severe renal impairment, kept on chronic haemodialysis (study was conducted in between sessions of hemodialysis).

Patients with abnormal liver function

In patients with severely impaired liver function is drastically reduced systemic clearance of ondansetron with increase in T1/2 to 15-32 h

Description pharmacological action:

Ondansetron is a selective antagonist of 5-HT3 receptors. Drugs for cytotoxic chemotherapy and radiotherapy may cause increased levels of serotonin, which by activation of vagal afferent fibers containing 5-HT3 receptors, causes a gag reflex. Ondansetron inhibits the appearance of the gag reflex by blockade of 5-HT3 receptors at the level of neurons as the Central nervous system and peripheral nervous system.

Indications:

• prevention and elimination of nausea and vomiting due to cytotoxic chemotherapy or radiotherapy
  
• prevention and elimination of postoperative nausea and vomiting (R-R in/in and/m introduction, lozenges, syrup).
  

Contraindications:

• hypersensitivity to any component of the drug
  
• pregnancy
  
• lactation
  
• children's age (suppositories)
  
• children up to age 2 years (lozenges, syrup — the safety and efficacy of not been studied).
  

Additionally, for R-RA in/in and/m introduction

Be used with caution in patients with cardiac arrhythmias and conduction, patients receiving antiarrhythmic agents and beta-blockers and patients with significant electrolyte disorders (very rarely with on/in the introduction of the Zofran was was transient ECG changes, including prolongation of the interval QT).

Side effects:

Lozenges, syrup, suppositories

Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis.

From the digestive system: hiccups, dry mouth, constipation or diarrhea, burning sensation in the anus and rectum after insertion of the suppository is sometimes asymptomatic transient increase in the activity of hepatic tests.

From the side of cardiovascular system: chest pain, in some cases with depression of the ST segment, arrhythmia, bradycardia, decrease in blood pressure.

From the nervous system: headache, dizziness, spontaneous movement disorders and seizures.

Other: flushed face, feeling of heat, temporary violation of visual acuity, hypokalemia, gipercreatininemia.

R-R in/in and/m introduction

Adverse events are presented below, categorized by frequency of occurrence. The frequency of occurrence as follows: very often — &ge1/10 often — &ge1/100 and <1/10 sometimes &ge1/1000 and <1/100 rare &ge1/10,000 and <1/1000 very rare <1/10000, including individual messages.

The immune system: rarely — hypersensitivity reactions of immediate type, in some cases severe, including anaphylaxis.

From the nervous system: very often — headache sometimes — convulsions, movement disorders (including extrapyramidal symptoms such as dystonia, oculogyric crisis (spasm of eyes) and dyskinesia) in the absence of persistent clinical consequences dizziness during rapid I/V administration.

From the side of organs of vision: rarely: transient visual disturbances (blurred vision), mainly during in/in the introduction is very rarely transient blindness, mainly during in/in the introduction. Most cases of blindness is well resolved within 20 minutes. Most patients had received chemotherapeutic drugs containing cisplatin. In some cases of transient blindness were cortical origin.

Of the cardiovascular system: sometimes- arrhythmia, chest pain, as accompanied by and not accompanied by a decrease of the ST segment, bradycardia, decrease in blood pressure often — hot flashes or hot flashes very rarely transient ECG changes including prolongation of the interval QT, mainly at/in the introduction.

The respiratory system of the chest and mediastinum: sometimes the hiccups.

By the blood: often — constipation.

The liver and biliary tract: sometimes — asymptomatic increases in liver samples (mainly observed in patients receiving chemotherapy with cisplatin).

General and local reactions: often — local reactions at the place on/in the introduction.

Drug interactions:

There is no evidence that ondansetron induces or inhibits the metabolism of other drugs commonly prescribed in combination with it.

Ondansetron is metabolized by multiple enzymes of cytochrome P450 (CYP3A4, CYP2D6 and CYP1A2). Inhibition or reduced activity of one enzyme usually kompensiruet other, therefore a significant decrease in the total clearance of ondansetron is unlikely. However, caution is required if joint application:

- with these enzyme inducers P450 (CYP2D6 and CYP1A2) as barbiturates, carbamazepine, carisoprodol, glutethimide, griseofulvin, nitrous oxide, papaverine, phenylbutazone, phenytoin (probably other hydantoins), rifampin, tolbutamide

 with such inhibitors of P450 enzymes (CYP2D6 and CYP1A2), as allopurinol, macrolide antibiotics, antidepressants, MAO inhibitors, chloramphenicol, cimetidine, oral contraceptives containing estrogens, diltiazem, disulfiram, valproic acid, sodium valproate, erythromycin, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil.

Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, tramadol and propofol (Diprivan).

Additionally, for R-RA in/in and/m introduction

Phenytoin, carbamazepine and rifampicin

Patients receiving potent inducers of CYP3A4 (phenytoin, carbamazepine, and rifampicin), the concentration of ondansetron in the blood was reduced.

Tramadol

There is evidence small studies indicate that ondansetron may reduce analgeziruuchee effect of tramadol.

Pharmaceutical compatibility with other drugs

Zofran at a concentration of 16 µg/ml and 160 µg/ml (corresponding to 8 mg/500 ml and 8 mg/50 ml respectively) pharmaceutically compatible and can be administered via a Y-shaped injector/drip in conjunction with the following drugs:

- cisplatin (at concentrations up to 0.48 mg/ml) for 1-8 h

- 5-fluorouracil (at a concentration of 0.8 mg/ml at a rate of 20 ml/h, higher concentrations of 5-fluorouracil can cause hair loss Zofran in sediment)

- carboplatin (at a concentration of 0.18–9.9 mg/ml) for 10-60 min.

- etoposide (0,144 in a concentration–0.25 mg/ml for 30-60 min)

- ceftazidime (dose of 0.25–2 g, in/in the bolus injection over 5 min)

- cyclophosphamide (in the dose of 0.1–1 g, in/in the bolus injection over 5 min)

- doxorubicin (at a dose of 10-100 mg, in/in the bolus injection over 5 min)

- dexamethasone: possible in/with the introduction of 20 mg dexamethasone slowly over 2-5 min. LS, you can enter using one dropper in the solution concentration of dexamethasone sodium phosphate can range from 32 micrograms to 2.5 mg/ml, Zofran 8 mg to 1 mg/ml.

Method of application and dose:

The solution for the on/in and/m introduction

Nausea and vomiting caused by chemotherapy and/or radiotherapy

The choice of dosage regimen is determined by the degree of emetogenic anticancer therapy.

Adults

Emetogenna chemotherapy and radiotherapy. The recommended dose is 8 mg, injected slowly in/in or/m immediately before chemotherapy or radiotherapy.

Highly pathogenic chemotherapy. Patients receiving vysokopatogennogo chemotherapy, for example cisplatin at high doses, Zofran may be administered as a single in/in or/m injection at a dose of 8 mg immediately before chemotherapy. Zofran at a dose of 8 to 32 mg must enter only through the on/in infusion after reconstitution of the drug in 50-100 ml 0.9% solution of sodium chloride or other compatible infusion solution for 15 min and more. Another method involves injection of Zofran dose 8 mg slowly in/in or/m immediately before chemotherapy, followed by administration of two injections of the drug in/in or/m in a dose of 8 mg every 2-4 h or continuous infusion of drug at a rate of 1 mg/h for 24 hours

In the case of vysokopatogennogo anticancer therapy, the effectiveness of Zofran can be reinforced with additional single on/in the introduction of dexamethasone sodium phosphate in a dose of 20 mg before chemotherapy. Oral or rectal dosage forms of Zofran is recommended to prevent delayed or continued vomiting after the first day after chemotherapy.

Children and adolescents (aged 6 months to 17 years). Children with body surface area less than 0.6 m2 an initial dose of 5 mg/m2 is administered in/in immediately before chemotherapy, followed by administration of Zofran oral dose of 2 mg (in the form of syrup) after 12 h for 5 days after treatment with the therapy continue taking the Zofran orally at a dose of 2 mg 2 times a day.

Children with body surface area of 0.6 to 1.2 m2 Zofran is introduced into/in a single dose of 5 mg/m2 immediately before chemotherapy, followed by administration of the drug orally at a dose of 4 mg after 12 h. Acceptance of Zofran oral dose of 4 mg 2 times a day can be continued for 5 days after chemotherapy.

Children with body surface area more than 1.2 m2 an initial dose of 8 mg is administered in/in immediately before chemotherapy, followed by administration of the drug orally at a dose of 8 mg every 12 hours taking Zofran orally at a dose of 8 mg 2 times a day can be continued for 5 days after chemotherapy.

Alternatively, children aged 6 months and older, the Zofran is injected into/in a single dose of 0.15 mg/kg (>8 mg) immediately before chemotherapy. This dose can be repeated every 4 hours, for a maximum of three doses in total. The acceptance of Zofran oral dose of 4 mg 2 times a day can be continued for 5 days after chemotherapy. The dose should not exceed that recommended for adults.

Patients of advanced age. Dosage adjustment Zofran is not required.

Patients with impaired renal function. Dosage adjustment Zofran is not required.

Patients with impaired liver function. Clearance of Zofran is significantly reduced and the elimination half-life increased in patients with human liver moderate or severe degree. Daily dose of Zofran should not exceed 8 mg.

Patients with a slow metabolism sparteine/debrisoquine

In patients with a slow metabolism sparteine and debrisoquine the half-life of ondansetron is not altered. Thus, with repeated administration of Zofran to patients its concentration in the plasma will not differ from that in the General population. Therefore, such patients correction daily dose or frequency of administration of ondansetron is not required.

Postoperative nausea and vomiting

Adults. To prevent nausea and vomiting in the postoperative period is recommended that a single I/m or slow I/V injection of Zofran dose 4 mg during induction narcosis.

For the treatment of nausea and vomiting postoperatively, Zofran is administered once in a dose of 4 mg I/m or slow I/V.

Children and adolescents (aged 1 month to 17 years). To prevent nausea and vomiting in the postoperative period in children subjected to surgical intervention under General anesthesia, Zofran can be administered in a dose of 0.1 mg/kg (maximum 4 mg) as a slow intravenous injection before, during or after induction of anesthesia or after the surgery. For the relief of nausea and vomiting, which developed in the postoperative period, it is recommended that a slow in/in the injection of Zofran dose of 0.1 mg/kg (maximum 4 mg).

Patients of advanced age. There is limited experience of Zofran for the prevention and relief of postoperative nausea and vomiting in the elderly, although the Zofran is well tolerated by patients over 65 years receiving chemotherapy.

Patients with impaired renal function. Correction doses of Zofran is not required.

Patients with impaired liver function. Clearance of Zofran is significantly reduced and the elimination half-life increased in patients with human liver moderate or severe degree. Daily dose of Zofran should not exceed 8 mg.

Patients with a slow metabolism sparteine/debrisoquine. In patients with a slow metabolism sparteine and debrisoquine the half-life of ondansetron is not altered. Therefore, with the reintroduction of such patients its concentration in the plasma will not differ from that in the General population. Therefore, such patients correction daily dose or frequency of administration of ondansetron is not required.

Pharmaceutical compatible

Dilution of injection solution may include the following solutions:

0.9% sodium chloride solution

- 5% dextrose

- ringer solution

- 10% solution of mannitol

- 0.3% solution of potassium chloride and 0.9% sodium chloride solution

- 0.3% solution of potassium chloride and 5% dextrose solution.

The infusion solution should be prepared directly before use. In case of need ready infusion solution can be stored until use within 24 h at a temperature of 2-8 °C. During the infusion of protection from light is not required diluted injectable solution retains its stability for at least for 24 h under natural light or normal lighting.

Lozenges and syrup

The ODT tablet is placed on the tip of the tongue, after the dissolution of her swallow.

Nausea and vomiting with cytotoxic chemotherapy or radiotherapy

The choice of dosage regimen is determined by emetogenicity anticancer therapy.

Adults: the daily dose usually is 8-32 mg.

We recommend the following modes:

- moderate emetogenic of chemotherapy and radiotherapy the recommended dose of 8 mg of ondansetron 1-2 hours prior to primary therapy followed by administration of another 8 mg orally after 12 h

- in case of high emetogenic chemotherapy the recommended dose of 24 mg ondansetron simultaneously with dexamethasone in a dose of 12 mg 1-2 hours before chemotherapy.

For the prevention of late or prolonged vomiting that occurs after 24 hours, you should continue taking Zofran orally at a dose of 8 mg 2 times a day for 5 days.

Children Zofran is usually administered in the form of solution for injection in a dose of 5 mg/m2 once/immediately before chemotherapy, followed by administration of an oral dose of 4 mg over 12 h After completion of chemotherapy should continue taking Zofran dose 4 mg 2 times a day for 5 days.

Nausea and vomiting in the postoperative period

Adults for prevention of nausea and vomiting in the postoperative period is recommended 16 mg of Zofran inside for 1 h before the anesthesia.

For the relief of postoperative nausea and vomiting used Zofran solution for injection.

Children for prevention and relief of postoperative nausea and vomiting Zofran is administered as an intravenous injection.

Patients of advanced age. Changes dosage not required.

Patients with renal insufficiency. Does not require special changes to the dosage, frequency of administration, or method of application.

Patients with impaired liver function. Daily dose of ondansetron should not exceed 8 mg.

Patients with a slow metabolism sparteine/debrisoquine. Correction daily dose or frequency of administration of ondansetron is not required.

Suppositories

Nausea and vomiting with cytotoxic chemotherapy or radiotherapy

The choice of dosage regimen is determined by emetogenicity anticancer therapy.

For adults we recommend the following modes:

- moderate emetogenna chemotherapy or radiotherapy, 16 mg of ondansetron (1 supp.) for 1-2 hours before the start of the primary therapy.

- in case of high emetogenic chemotherapy the recommended dose of 16 mg (1 supp.) simultaneously with I/V introduction of 20 mg dexamethasone for 1-2 hours before start of chemotherapy.

For the prevention of late or prolonged vomiting occurring 24 hours after chemotherapy or radiotherapy, should continue taking the drug at a dose of 16 mg (1 supp.) 1 time a day for 5 days. Instead of a suppository can also be assigned Zofran orally in the form of tablets or syrup.

Children. The in zofran suppositories are not recommended for use in children.

Children Zofran is prescribed in other pharmaceutical forms: pills or syrup for oral administration or liquid for parenteral administration.

Patients of advanced age. Changes dosage not required.

Patients with renal insufficiency. Does not require special changes to the dosage, frequency of administration, or method of application.

Patients with impaired liver function. The use of suppositories is not recommended because the daily dose of ondansetron for this category of patients should not exceed 8 mg/day.

Patients with a slow metabolism sparteine/debrisoquine. Correction daily dose or frequency of administration of ondansetron is not required.

Overdose:

Symptoms: in most cases similar to adverse reactions when using the drug in the recommended doses. There is limited experience of ondansetron overdose.

Treatment: specific antidote for Zofran is not, so if you suspect an overdose recommended symptomatic and supportive therapy. Use of ipecac overdose of Zofran should not, because its effectiveness is unlikely due to the antiemetic effects of Zofran.

Special instructions:

Marked allergic reactions to ondansetron in patients with a history of hypersensitivity to other antagonists 5HT3 receptors.

As ondansetron increases the time of passage of contents on a thick gut, patients with signs of bowel obstruction after treatment require regular monitoring.

Lozenges contain aspartame, which should be taken with caution in patients with phenylketonuria.

Lozenges you don't have to squeeze out of the foil, to get them just before use.

Currently, there are limited data on the use of ondansetron (R-R in/in and/m introduction) in children under the age of 1 month.

Pharmaceutical precautions

Zofran should not be administered in the same syringe or in an infusion solution with other drugs.

Effects on ability to drive and work with moving mechanisms

Zofran has sedative effect and does not affect the ability of patients to drive vehicles or doing other potentially hazardous activities, require high concentration and psychomotor speed reactions.