ZOFRAN

What it is

ZOFRAN contains ondansetron hydrochloride dihydrate (in injections, tablets and oral liquid formulations) or ondansetron (in suppositories and wafers). Ondansetron is a potent, highly selective 5HT3 receptor-antagonist.

Approved indications

— Prevention and treatment of nausea and vomiting induced by cytotoxic therapy and radiotherapy. — Prevention and treatment of post-operative nausea and vomiting (injection formulation only).

Dosing overview

The route of administration and dose of ZOFRAN should be flexible in the range of 8–32 mg a day, with the lowest effective dose being used. For chemotherapy and radiotherapy-induced nausea and vomiting in adults, a single dose of 8 mg of ondansetron should be administered as a slow intravenous injection in not less than 30 seconds, immediately before treatment. Alternatively, two oral doses of 8 mg each at 12 hourly intervals may be given, the first dose being administered 2 hours prior to chemotherapy or radiotherapy, or a single ondansetron 16 mg suppository, 2 hours before treatment. To protect against delayed emesis after the first 24 hours, ondansetron should be continued orally at a dosage of 8 mg twice daily, or given rectally as a 16 mg suppository once daily, for up to 5 days after a course of treatment. For highly emetogenic chemotherapy, an alternative to intravenous treatment is a single oral dose of up to 24 mg ondansetron taken with oral dexamethasone 12 mg, 1–2 hours before commencing chemotherapy. For post-operative nausea and vomiting prevention in adults, ondansetron may be administered as a single dose of 4 mg by intramuscular or slow intravenous injection at induction of anaesthesia. For treatment of established post-operative nausea and vomiting, a single dose of 4 mg given by intramuscular or slow intravenous injection is recommended in most patients. A single dose of intravenous ondansetron given for the prevention of chemotherapy-induced nausea and vomiting in elderly patients aged 75 years or older must not exceed 8 mg (infused over at least 15 minutes). A single dose of intravenous ondansetron given for the prevention of chemotherapy-induced nausea and vomiting in adults aged less than 75 years must not exceed 16 mg (infused over at least 15 minutes).

Key safety warnings

Ondansetron causes a dose-dependent prolongation of the electrocardiographic-corrected QT interval, which can lead to Torsade de Pointes, a potentially life-threatening heart arrhythmia. Ondansetron should be avoided in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including those 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. Serotonin syndrome has been described following the concomitant use of ondansetron and other serotonergic drugs. If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised. Cases of myocardial ischaemia have been reported in patients treated with ondansetron. In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of ondansetron. Patients should be alerted to the signs and symptoms of myocardial ischaemia. As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.

Contraindications

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

PBS listing

ZOFRAN tablets 8 mg are listed on the PBS with 3 items under streamlined restrictions at an ex-manufacturer price of A$4.33. Tablets 4 mg are listed with 3 PBS items under streamlined restrictions at an ex-manufacturer price of A$3.50. ZOFRAN ZYDIS wafers 8 mg are listed with 1 PBS item under streamlined restriction at an ex-manufacturer price of A$16.59, whilst 4 mg wafers are listed with 1 PBS item at an ex-manufacturer price of A$11.97. Oral liquid (syrup) 4 mg per 5 mL is listed with 3 PBS items under streamlined and restricted conditions at an ex-manufacturer price of A$80.78.

Regulatory history

ZOFRAN was first approved on the Australian Register of Therapeutic Goods on 17 April 1991, with initial registrations for 4 mg and 8 mg tablets in both bottle and blister pack formats, as well as injection formulations. The 24 mg tablet was registered on 26 March 1999. In December 2022, the PBAC recommended a change for expanded PBS listing to include utilisation of ondansetron for nausea and vomiting associated with cytotoxic chemotherapy, including methotrexate, for juvenile autoimmune conditions.