Zofran Injection 2 mg/ml

/ Novartis

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 Zofran should be flexible in the range of 8-32mg a day and selected as shown below.
Emetogenic chemotherapy and radiotherapy: Zofran can be given either by tablets, intravenous or intramuscular administration.
For most patients receiving emetogenic chemotherapy or radiotherapy, Zofran 8mg should be administered as a slow intravenous injection (in not less than 30 seconds) or intramuscular injection, immediately before treatment, followed by 8mg orally twelve hourly. To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with Zofran 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, Zofran can be given either by oral, intravenous or intramuscular administration. Zofran 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) or intramuscular injection immediately before chemotherapy.
– A dose of 8mg by slow intravenous injection (in not less than 30 seconds) or intramuscular injection immediately before chemotherapy, followed by two further intravenous injection( in not less than 30 seconds) or intramuscular doses 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 Zofran may be followed by two additional 8mg intravenous doses (in not less than 30 seconds) or intramuscular doses 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 Zofran 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 Zofran should be continued for up to 5 days after a course of treatment.
Paediatric 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. Zofran 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 Zofran in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of Zofran for radiotherapy-induced nausea and vomiting in children.
Dosing by BSA: Zofran 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 (for full details see prescribing information). The total dose over 24 hours (given as divided doses) 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. Zofran 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 (for full details see prescribing information). The total dose over 24 hours (given as divided doses) 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 Zofran 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 Zofran 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 is required.
Post-Operative Nausea and Vomiting (PONV)
Adults: For the prevention of PONV Zofran can be administered orally or by intravenous or intramuscular injection. Zofran may be administered as a single dose of 4mg given by intramuscular or slow intravenous injection at induction of anaesthesia. For treatment of established PONV a single dose of 4mg given by intramuscular or 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 Zofran 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 Zofran 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 Zofran in treatment of PONV in children below 2 years of age.
Elderly: There is limited experience in the use of Zofran in the prevention and treatment of PONV in the elderly; however Zofran 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 Zofran 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.
For full details see prescribing information.

Adults: Indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Zofran is indicated for the prevention and treatment of post-operative nausea and vomiting (PONV).
Paediatric Population: Indicated for the 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.

Concomitant use with apomorphine. Hypersensitivity to any component of the preparation.

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. Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine 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 Zofran 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. 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 Zofran and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Zofran and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Zofran is used concomitantly with other serotonergic drugs.
As ondansetron is known to increase large bowel transit time, patients with signs of sub-acute 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 hour 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.
Sodium: Zofran Injection contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium- free”.

Very common: Headache.
Common: Sensation of warmth or flushing. Constipation. Local IV injection site reactions.
See prescribing information for full details.

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, lidocaine, 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. 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.
Serotonergic Drugs: Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs).
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.

Pregnancy: Based on human experience of epidemiological studies, ondansetron is suspected to cause orofacial malformations when administered during first trimester of pregnancy.
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 Zofran should not breast-feed their babies.
See prescribing information for full details.

Symptoms and Signs: 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 the QT interval in a dose-dependent fashion. ECG monitoring is recommended in cases of overdose.
Paediatric population: Paediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeded 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.
Further management should be as clinically indicated or as recommended by the poisons centre, where available.
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.

Incompatibilities: Zofran injection should not be administered in the same syringe or infusion as any other medication. Ondansetron injection should only be mixed with those infusion solutions that are recommended.
Storage: Protect from light. Store below 30ºC. Dilutions of Zofran injection in compatible intravenous infusion fluids are stable under normal room lighting conditions or daylight for at least 24 hours, thus no protection from light is necessary while infusion takes place.