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  • Ondansetron Fresenius 2 mg/ml
    / Medic Trim Healthcare


    Active Ingredient
    Ondansetron (as HCl dihydrate) 2 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Ampoule

    2 ml X 2 mg/ml

    partial basket chart 51431 15429

    Ampoule

    4 ml X 2 mg/ml

    partial basket chart 51445 15430

    Dosage

    For intravenous injection or for intravenous infusion after dilution.
    Chemotherapy and Radiotherapy:
    Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of Ondansetron should be flexible in the range of 8-32mg a day and selected as shown below.
    Emetogenic chemotherapy and radiotherapy: Ondansetron can be given by intravenous administration. For most patients receiving emetogenic chemotherapy or radiotherapy, Ondansetron 8mg should be administered as a slow intravenous injection in not less than 30 seconds immediately before treatment, followed by 8mg orally twelve hourly. To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with Ondansetron should be continued for up to 5 days after a course of treatment.
    Highly emetogenic chemotherapy: For patients receiving highly emetogenic
    chemotherapy, e.g. high-dose cisplatin, Ondansetron can be given by intravenous administration. Ondansetron has been shown to be equally effective in the following dose schedules over the first 24 hours of chemotherapy: A single dose of 8mg by slow intravenous injection (in not less than 30 seconds) immediately before chemotherapy. A dose of 8mg by slow intravenous injection immediately before chemotherapy in not less than 30 seconds, followed by two further intravenous doses (in not less than 30 seconds) of 8mg four hours apart, or by a constant infusion of 1mg/hour for up to 24 hours. A maximum initial intravenous dose of 16mg diluted in 50-100ml of saline or other compatible infusion fluid and infused over not less than 15 minutes immediately before chemotherapy. The initial dose of ondansetron may be followed by two additional 8mg intravenous doses (in not less than 30 seconds) four hours apart. A single dose greater than 16 mg must not be given due to dose dependent increase of QT-prolongation risk. The selection of dose regimen should be determined by the severity of the emetogenic challenge. The efficacy of Ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20mg administered prior to chemotherapy. To protect against delayed or prolonged emesis after the first 24 hours, oral or treatment with Ondansetron should be continued for up to 5 days after a course of treatment.
    Pediatric Population:
    CINV in children aged 6 months and adolescents: The dose for CINV can be calculated based on body surface area (BSA) or weight – see below. Weight-based dosing results in higher total daily doses compared to BSA-based dosing. Ondansetron injection should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion fluid and infused intravenously over not less than 15 minutes. There are no data from controlled clinical trials on the use of Ondansetron in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of Ondansetron for radiotherapyinduced nausea and vomiting in children.
    Dosing by BSA: Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m2. The single intravenous dose must not exceed 8 mg. Oral dosing can commence twelve hours later and may be continued for up to 5 days. The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.
    BSA-based dosing for Chemotherapy – Children aged 6 months and adolescents:
    BSA< 0.6 m2: Day 1 (a,b) – give 5 mg/m2 I.V. plus 2 mg P.O. after 12 hrs, and on  Days 2-6(b) give 2 mg P.O. every 12 hrs.
    BSA≥ 0.6 m2: Day 1 (a,b) – give 5 mg/m2 I.V. plus 4 mg P.O. after 12 hrs, and on Days 2-6(b) give 4 mg P.O. every 12 hrs. a The intravenous dose must not exceed 8mg. b The total dose over 24 hours must not exceed adult dose of 32 mg.
    Dosing by bodyweight: Weight-based dosing results in higher total daily doses compared to BSA based Dosing. Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The single intravenous dose must not exceed 8 mg. Two further intravenous doses may be given in 4-hourly intervals. Oral dosing can commence twelve hours later and may be continued for up to 5 days. The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.
    Weight-based dosing for Chemotherapy – Children aged 6 months and adolescents: Weight ≤ 10 kg : Day 1 (a,b)– give  Up to 3 doses of 0.15 mg/ kg every 4 hrs, and on Days 2-6(b) give 2 mg p.o. every 12 hrs. Weight > 10 kg : Day 1 (a,b)– give  Up to 3 doses of 0.15 mg/ kg every 4 hrs, and on Days 2-6(b) give 4 mg p.o. every 12 hrs. a The intravenous dose must not exceed 8mg. b The total dose over 24 hours must not exceed adult dose of 32 mg.
    Elderly:
    In patients 65 to 74 years of age, the dose schedule for adults can be followed. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid and infused over 15 minutes.
    In patients 75 years of age or older, the initial intravenous dose of ondansetron should not exceed 8 mg. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid and infused over 15 minutes. The initial dose of 8 mg may be followed by two further intravenous doses of 8 mg, infused over 15 minutes and given no less than four hours apart.
    Patients with Renal Impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.
    Patients with Hepatic Impairment: Clearance of Ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8mg should not be exceeded and therefore parenteral or oral administration is recommended.
    Post-Operative Nausea and Vomiting (PONV):
    Adults: Ondansetron may be administered as a single dose of 4mg given by slow intravenous injection at induction of anaesthesia. For treatment of established PONV a single dose of 4mg given by slow intravenous injection is recommended.
    Paediatric population:
    PONV in children aged 1 month and adolescents: For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, a single dose of Ondansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg either prior to, at or after induction of anaesthesia. For the treatment of PONV after surgery in paediatric patients having surgery performed under general anaesthesia, a single dose of Ondansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg. There are no data from clinical trials on the use of Ondansetron in the treatment of PONV in children below 2 years of age.
    Elderly: There is limited experience in the use of Ondansetron in the prevention and treatment of PONV in the elderly, however Ondansetron is well tolerated in patients over 65 years receiving chemotherapy.
    Patients with Renal Impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.
    Patients with Hepatic Impairment: Clearance of Ondansetron is significantly reduced and serum half life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8mg should not be  exceeded and therefore parenteral or oral administration is recommended.
    Patients with poor Sparteine/Debrisoquine Metabolism: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing are required.


    Indications

    Adults: Management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Prevention and treatment of post-operative nausea and vomiting (PONV).
    Paediatric Population: Management of chemotherapy-induced nausea and vomiting (CINV) in children aged ≥6 months and for the prevention and treatment of PONV in children aged ≥ 1 month.


    Contra-Indications

    Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated. Hypersensitivity to any component of the preparation.         


    Special Precautions

    Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists.
    Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.
    Ondansetron prolongs the QT interval in a dose-dependent manner. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.
    Hypokalemia and hypomagnesemia should be corrected prior to ondansetron administration.
    1 ml solution for injection contains 3.34 mg of sodium as sodium citrate dihydrate and sodium chloride. To be taken into consideration by patients on a controlled sodium diet.
    There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of ondansetron and other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron alone has also been reported.
    The majority of reports of serotonin syndrome related to 5-HT receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised.
    Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Ondansetron and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Ondansetron – and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Ondansetron is used concomitantly with other serotonergic drugs.
    As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
    In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.
    Paediatric Population: Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired. hepatic function.
    CINV: When calculating the dose on an mg/kg basis and administering three doses at 4-hourly intervals, the total daily dose will be higher than if one single dose of 5mg/m2 followed by an oral dose is given. The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials. Cross-trial comparison indicates similar efficacy for both regimens.


    Side Effects

    Headache, Sensation of warmth or flushing, Constipation, Local I.V. Injection site reactions.
    See prescribing information for full details.


    Drug interactions

    There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly co-administered with it. Specific studies have shown that there are no interactions when ondansetron is administered with alcohol, temazepan, furosemide, alfentanil, tramadol, morphine, lignocaine, thiopental, or propofol.
    Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.
    Apomorphine: Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.
    Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.
    Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.
    Caution should be exercised when ondansetron is coadministered with drugs that prolong the QT interval and/or cause electrolyte abnormalities. Use of Ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of Ondansetron with cardiotoxic drugs (e.g. anthracyclines such as doxorubicin, daunorubicin or trastuzumab), antibiotics (such as erythromycin) antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias.
    There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs).          


    Pregnancy and Lactation

    Pregnancy: The safety of ondansetron for use in human pregnancy has not been established. the use of ondansetron in pregnancy is not recommended.
    Lactation: Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving Ondansetron should not breast-feed their babies.
    See prescribing information for full details.  


    Overdose

    There is limited experience of ondansetron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses.
    Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second degree AV block.Ondansetron prolongs QT interval in a dose-dependent manner. ECG monitoring is recommended in cases of overdose. Paediatric population: Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 4 mg/kg) in infants and children aged 12 months to 2 years.
    Reported symptoms included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.
    Treatment: There is no specific antidote for ondansetron, therefore in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate. The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.


    Important notes

    Storage: Protect from light. Store below 30ºC. Keep the ampoules in the outer carton in order to protect from light.


    Manufacturer
    LABESFAL- Laboratorios Almiro S.A Fresenius Kabi Group
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