Zofran Tablets 4 mg, 8 mg

/ Novartis

Chemotherapy and radiotherapy induced nausea and vomiting
Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The selection of dose regimen should be determined by the severity of the emetogenic challenge.
Emetogenic Chemotherapy and Radiotherapy: Zofran can be given either by oral (tablets), intravenous or intramuscular administration.
For oral administration: 8mg taken 1 to 2 hours before chemotherapy or radiation treatment, followed by 8mg every 12 hours for a maximum of 5 days to protect against delayed or prolonged emesis.
For highly emetogenic chemotherapy: To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with Zofran may be continued for up to 5 days after a course of treatment.
The recommended dose for oral administration is 8mg to be taken twice daily.
Paediatric Population: Ondansetron may be administered as a single intravenous dose of 5mg/m² immediately before chemotherapy, followed by 4mg orally twelve hours later. 4mg orally twice daily can be continued for up to 5 days after a course of treatment.
Elderly: Zofran is well tolerated by patients over 65 years. No alteration of oral dose or frequency of administration is required.
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.
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
Adults: For the prevention of PONV: Zofran can be administered orally or by intravenous or intramuscular injection. For oral administration: 16mg taken one hour prior to anaesthesia.
For the treatment of established PONV: Intravenous or intramuscular administration is recommended.
Children and Adolescents aged 2 years and over: No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post operative nausea and vomiting; slow i.v. injection is recommended for this purpose.
Elderly: There is limited experience in the use of Zofran in the prevention and treatment of post-operative nausea and vomiting 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.
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.

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

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-HT3 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 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.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Very common: Headache.
Common: Sensation of warmth or flushing. Constipation.
For full details see prescribing information.

There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly coadministered with it. Specific studies have shown that there are no pharmacokinetic interactions when ondansetron is administered with alcohol, temazepam, frusemide, tramadol 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 ondansetron 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 cases consistent with serotonin syndrome have been reported after
inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 5 mg/kg) in young children. 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.

Storage: Store below 30°C.