ZOFRAN
Active material: Ondansetron
When ATH: A04AA01
CCF: Antiemetic drugs of the central action, blocking serotonin receptors
ICD-10 codes (testimony): R11
When CSF: 11.06.01
Manufacturer: GlaxoSmithKline Trading Company (Russia)
Pharmaceutical form, composition and packaging
Solution for in / and the / m clear, colorless, virtually free of inclusions.
| 1 ml | 1 amp. | |
| Ondansetron hydrochloride dihydrate | 2.5 mg | 5 mg, |
| that corresponds to the content of ondansetron | 2 mg | 4 mg |
Excipients: citric acid monohydrate, sodium citrate, sodium chloride.
2 ml – ampoule (5) – packs cardboard.
Solution for in / and the / m clear, colorless, virtually free of inclusions.
| 1 ml | 1 amp. | |
| Ondansetron hydrochloride dihydrate | 2.5 mg | 10 mg, |
| that corresponds to the content of ondansetron | 2 mg | 8 mg |
Excipients: citric acid monohydrate, sodium citrate, sodium chloride, water d / and.
4 ml – ampoule (5) – packs cardboard.
Pharmacological action
Antiemetics, selective serotonin 5HT3-receptors.
Ondansetron is a potent highly selective antagonist of the 5HT3-receptors. The mechanism of suppression of nausea and vomiting is not known exactly. When radiation therapy and the use of chemotherapy drugs can cause release of serotonin (5NT) in the small intestine, causes a gag reflex by activating 5HT3-receptors and excitation of afferent endings of the vagus nerve. Ondansetron blocks the initiation of this reflex. The activation of the afferent endings of the vagus nerve, in turn, can cause 5HT release in the rear bottom field of the fourth ventricle (The last area), and, Consequently, run the gag reflex via a central mechanism. Thus, ondansetron action to suppress nausea and vomiting, sprovotsirovannыh tsitotoksicheskoy himioterapiey and radioterapiey, apparently, It is carried out thanks to antagonize 5HT3-receptor neurons, located at the periphery, and in the central nervous system.
Ondansetron not influence the concentration of prolactin in plasma.
Pharmacokinetics
Ondansetron pharmacokinetic parameters are not changed when multiple injections.
Absorption
Ondansetron has the same systemic exposure with the / m and / in the introduction.
Distribution
Ondansetron has a moderate ability to bind to plasma proteins (70-76%). The distribution of ondansetron is similar with the / m and / in the introduction in adults. Vd at equilibrium is about 140 l.
Metabolism
Ondansetron is metabolized, mainly, in the liver, with the participation of several enzymes. The absence of CYP2D6 enzyme (Polymorphisms spartyein / dyebrizokhinovogo tipa) It has no effect on the pharmacokinetics of ondansetron.
Deduction
Ondansetron is derived from the systemic circulation, primarily, by metabolism in the liver. Less 5% of the administered dose is excreted unchanged in the urine. T1/2 ondansetron after the / m, and after i / v administration is about 3 no.
Pharmacokinetics in special clinical situations
The pharmacokinetics of ondansetron depends on the sex of patients. Women had lower systemic clearance and Vd (figures adjusted for body weight), than men.
In a clinical study, children aged 1 to 24 Months (51 patient) Ondansetron was obtained at a dose of 0.1 mg / kg or 0.2 mg / kg to surgery. Patients aged 1 to 4 Months clearance was approximately 30% less, than in patients between the ages of 5 to 24 Months, but comparable with the indicator in patients between the ages of 3 to 12 years (correction parameters depending on the body weight). T1/2 in patients aged 1-4 m averaged 6.7 no; age groups 5-24 months and 3-12 years – 2.9 no. Patients aged 1 to 4 Months dose adjustment is required, is used as a single in / introduction of ondansetron for the treatment of postoperative nausea and vomiting in these patients. Differences pharmacokinetic parameters partly due to higher Vd patients aged 1 to 4 Months.
In a study in children 3-12 years (21 patient), undergoing elective surgery under general anesthesia, the absolute values of clearance and Vd ondansetron after a single on / in a dose of 2 mg (from 3 to 7 years) or 4 mg (from 8 to 12 years) They were reduced compared with the values in adults. Both parameters were increased linearly as a function of body weight, in patients aged 12 years, these values approach the value in adults. When the correction values of clearance and Vd depending on the body weight of these parameters were similar in different age groups. Calculation of the dose given body weight (0.1 mg / kg, a maximum of 4 mg) compensates for these changes and ondansetron systemic exposure in children.
It was held at the population pharmacokinetic analysis 74 patients aged 6 to 48 Months, which I / ondansetron is administered at a dose of 0.15 mg / kg every 4 hours in an amount 3 doses for relief of nausea and vomiting, caused by chemotherapy, and 41 patients aged 1 to 24 months after surgery, injected with a single dose of ondansetron 0.1 mg / kg or 0.2 mg / kg. Based on the pharmacokinetic parameters in this group of patients aged 1 to 48 months administration of ondansetron in / dose 0.15 mg / kg every 4 hours in an amount 3 doses should result in achieving systemic exposure (AUC), comparable to that, which is observed when using the drug at the same dose in children aged from 5 to 24 months during surgical procedures, as well as in previous studies in children with cancer (aged 4 to 18 years) and during surgery (aged 3 to 12 years).
Research, conducted in elderly patients, We showed weak, clinically insignificant, age-dependent increase in T1/2 ondansetrona.
In patients with moderate renal impairment (creatinine clearance 15-60 ml / min) at / in the introduction of ondansetron reduced both systemic clearance, and Vd ondansetrona, It is resulting in a small and clinically insignificant increase its T1/2 (to 5.4 no). The pharmacokinetics of ondansetron when / in the introduction remained virtually unchanged in patients with severely impaired renal function, on chronic hemodialysis (Research carried out in the breaks between sessions of hemodialysis).
In patients with severely impaired hepatic function sharply reduced systemic clearance of ondansetron with T1/2 to 15-32 no.
Testimony
- Prevention and elimination of nausea and vomiting, caused by chemotherapy or radiotherapy cytostatic, and post-operative nausea and vomiting.
Dosage regimen
Nausea and vomiting, caused by chemotherapy and / or radiotherapy
Selection of the dosing regimen is determined emetogenic anticancer therapy.
Adult
At moderately emetogenic chemotherapy or radiotherapy preparation is administered in a dose of 8 mg / in (jet slowly) or / m immediately before chemotherapy- or radiotherapy.
Patients, receiving vysokoemetogennuyu chemotherapy, eg, high-dose cisplatin, Zofran® It can be administered as a single in / or V / m at a dose of injection 8 mg immediately before chemotherapy. Zofran® in a dose of 8 mg 32 mg should be administered only by the I / infusion after reconstitution of the drug in 50-100 ml 0.9% sodium chloride, or other compatible infusion solution for 15 min or more. Another method is the introduction of Zofran® dose 8 slowly mg / w or w / o immediately before chemotherapy, followed by the designation of two injections / O or V / m at a dose 8 mg every 2-4 h or the use of continuous infusion of the drug at a rate of 1 mg / h for 24 no.
In the case of tumor therapy effectiveness vysokoemetogennoy Zofran® It can be strengthened further by a single I / dexamethasone sodium phosphate at a dose 20 mg before chemotherapy. Oral or rectal dosage forms Zofran® recommended for prevention of delayed or continuing vomiting after the first day after chemotherapy.
Children and adolescents (aged 6 Months before 17 years)
Babies with body surface area of less than 0.6 m2 starting dose 5 mg / m2 introduced in / directly before chemotherapy, followed by taking Zofran® oral dose 2 mg (in the form of a syrup) through 12 no. During 5 days after treatment continue therapy, taking Zofran® oral dose 2 mg 2 times / day.
Babies with body surface area 0.6-1.2 m2 Zofran® introduced in / single dose 5 mg / m2 immediately before chemotherapy, followed by taking the drug orally at a dose 4 mg after 12 no. Admission Zofran® oral dose 4 mg 2 times / day may be extended for a further 5 days after a course of chemotherapy.
Babies with a body surface area 1.2 m2 starting dose 8 mg administered in / directly before chemotherapy, followed by taking the drug orally at a dose 8 mg after 12 no. Admission Zofran® oral dose 8 mg 2 times / day may be extended for a further 5 days after a course of chemotherapy.
Alternatively for children 6 months and older Zofran® introduced in / single dose 0.15 mg / kg (no more 8 mg) immediately before chemotherapy. This dose can be administered again every 4 no, for a maximum of three doses in total. Admission Zofran® oral dose 4 mg 2 times / day may be extended for a further 5 days after a course of chemotherapy. The dosage should not exceed the recommended adult.
Other categories of patients
In patients Seniors change the dosing is not required.
Patients with impaired renal function dose adjustment Zofran® not required.
At hepatic dysfunction clearance of ondansetron significantly reduced, T1/2 increased in patients with impaired liver function moderate to severe. The daily dose of Zofran® should not exceed 8 mg.
Patients with slow metabolism of sparteine / debrizohina
In patients with slow metabolism and sparteine debrizohina T1/2 Ondansetron is not changed. Hence, repeated administration Zofran® plasma concentrations will not differ from that of the general population. Therefore, such patients correction daily dose or frequency of administration of ondansetron is not required.
Postoperative nausea and vomiting
Adult
To prevent nausea and vomiting in the postoperative period It recommended a single on / m or slow I / injection Zofran® dose 4 mg during induction of anesthesia.
To treat nausea and vomiting in the postoperative period Zofran® administered single dose of 4 mg / m or slow I /.
Children and adolescents (aged 1 Months before 17 years)
To prevent nausea and vomiting in the postoperative period children, undergoing surgery under general anesthesia, Zofran® can be administered at a dose of 0.1 mg / kg (a maximum of 4 mg) as a slow I / injection to, during or after induction of anesthesia and after surgery.
To relief of nausea and vomiting, developed in the postoperative period, recommended slow I / injection Zofran® dose 0.1 mg / kg (a maximum of 4 mg).
Other categories of patients
There is limited experience with the use of Zofran® to prevention and treatment of postoperative nausea and vomiting in elderly patients, although Zofran® well tolerated by patients over 65 years, receiving chemotherapy.
Patients with impaired renal function dose adjustment Zofran® not required.
At hepatic dysfunction clearance of ondansetron significantly reduced, T1/2 increased in patients with impaired liver function moderate to severe. The daily dose of Zofran® should not exceed 8 mg.
Patients with slow metabolism of sparteine / debrizohina
In patients with slow metabolism and sparteine debrpzohina T1/2 Ondansetron is not changed. Hence, repeated administration Zofran® plasma concentrations will not differ from that of the general population. Therefore, such patients correction daily dose or frequency of administration of ondansetron is not required.
Terms of use of the drug
Injectable solution for dilution may be used the following solutions: 0.9% sodium chloride solution, 5% Dextrose, Ringer, 10% mannitol solution, 0.3% solution of potassium chloride and 0.9% sodium chloride solution, 0.3% solution of potassium chloride and 5% Dextrose.
The infusion solution should be prepared immediately before use. If necessary, the solution is ready for infusion may be stored prior to use as much as possible during the 24 hours at 2-8 ° C. During infusion light shielding is not required; diluted injectable solution remains stable for at least 24 h under the natural light or normal light.
Side effect
Adverse events, shown below, classified by frequency of occurrence. Incidence is defined as follows:: Often (≥1/10), often (≥1 / 100 and <1/10), sometimes (≥1 / 1000 <1/100), rarely (≥1/10 000 and <1/1000), rarely (<1/10 000), including isolated reports.
On the part of the immune system: rarely – immediate hypersensitivity reactions, in some cases severe, including anaphylaxis.
From the nervous system: Often – headache; sometimes – convulsions, movement disorders (including extrapyramidal symptoms, such as dystonia, oculogyric crisis / spasm gaze / and dyskinesia) in the absence of persistent clinical sequelae; rarely - dizziness during rapid on / in the.
On the part of the organ of vision: rarely – transient visual disturbances (blurred vision), mainly, during on / in the; rarely – tranzitornaya blindness, mainly, during on / in the. Most of the cases of blindness successfully resolved within 20 m. Most of the patients received chemotherapy drugs, containing cisplatin. In some cases, transient cortical blindness was genesis.
Cardio-vascular system: sometimes – arrhythmia, chest pain, it is accompanied, and not accompanied by ST-segment depression, bradycardia, decrease in blood pressure; often – hot flashes or flushes; rarely – transient ECG changes, including the prolongation of the interval QT, predominantly, at / in the introduction.
From the digestive system: often – constipation; sometimes - asymptomatic increase of liver function tests (primarily, It was observed in patients, receiving chemotherapy with cisplatin).
Local reactions: often – local reaction at the site on / in the.
Other: sometimes – Ikotech.
Contraindications
- Pregnancy;
- Lactation (breast-feeding);
- Hypersensitivity to the drug.
FROM caution the drug should be used in patients with impaired cardiac rhythm and conduction, patients, receiving antiarrhythmic drugs and beta-blockers and patients with significant electrolyte disturbances (very rarely with a / in the introduction of Zofran® It has been reported transient ECG changes, including the prolongation of the interval QT).
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation (breast-feeding).
Cautions
There have been reports of the occurrence of hypersensitivity reactions to ondansetron in patients, with a history of sensitivity to other selective antagonists of the 5HT3-receptors.
Since it is known, that ondansetron increases the passage of the contents of the colon, in the case of the drug in patients with symptoms of sub-acute intestinal obstruction should be regularly monitored.
Zofran® should not be administered in the same syringe or an infusion solution with other drugs.
Use in Pediatrics
Currently, there are limited data from the use of ondansetron children under the age of 1 Months.
Effects on ability to drive vehicles and management mechanisms
Zofran® no sedative effect and does not affect the patients' ability to drive vehicles or engage in other potentially hazardous activities, require high concentration and speed of psychomotor reactions.
Overdose
Currently, few data on overdose of ondansetron. In most cases, the observed symptoms of overdose coincided with adverse reactions, arise when taking Zofran® at recommended doses.
Treatment: specific antidote for Zofran® no, so if you suspect an overdose recommended symptomatic and supportive therapy.
Drug Interactions
There is no evidence, ondansetron that induces or inhibits the metabolism of other drugs, often prescribed in combination with it.
According to special studies found, ondansetron that does not react with ethanol, temazepamom, furosemidom, tramadolom and propofolom.
Ondansetron is metabolized by several cytochrome P450 isoenzymes system (CYP3A4, CYP2D6 и CYP1A2). Due to the variety of isoenzymes, capable of metabolizing ondansetron, isoenzyme inhibition or reduction of activity of one of the isoenzymes (eg, a genetic deficiency of CYP2D6) usually compensated by other isoenzymes, whereby changes in the total clearance of ondansetron or absent, or minor and require little or no dose adjustment.
Patients, receiving strong CYP3A4 inducers (phenytoin, carbamazepine and rifampicin), ondansentrona concentration in the blood was reduced.
There is evidence of small studies, indicating, that ondansetron may reduce the analgesic effect of tramadol.
Pharmaceutical interaction
Pharmaceutically compatible with other medicaments: Zofran® concentration 16 ug / ml 160 ug / ml (corresponding 8 mg / 500 ml 8 mg / 50 ml, respectively) pharmaceutically compatible and can be administered through a Y-injector intravenously in conjunction with the following medicines:
- Cisplatin (at a concentration of 0.48 mg / ml) during 1-8 no;
- 5-ftoruraцil (at a concentration of 0.8 mg / ml at a rate 20 ml / h – higher concentrations of 5-fluorouracil can cause loss Zofran® precipitate);
- Karʙoplatin (concentration 0.18-9.9 mg / ml) during 10-60 m;
- Etoposide (concentration 0.144-025 mg / ml for 30-60 m);
- Цeftazidim (dose 0.25-2 g, a / in a bolus injection over a 5 m);
- Cyclophosphamide (dose 0.1-1 g, a / in a bolus injection over a 5 m);
- Doxorubicin (dose 10-100 mg, a / in a bolus injection over a 5 m);
- Dexamethasone (perhaps in / introduction 20 mg dexamethasone medlenno, during 2-5 m). Drugs can be administered through a drip, wherein the concentration of dexamethasone in the solution of sodium phosphate may be from 32 micrograms to 2.5 mg / ml, Zofran® – from 8 micrograms to 1 mg / ml.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children, dark place at temperatures not above 30 ° C. Shelf life - 3 year.
