Kytril (Mayne Pharma)
ampoules containing 3 mg/3 mL
2 mg tablets
Approved indications: nausea and vomiting
Australian Medicines Handbook section 12.3.4
Granisetron is another 5HT3 antagonist (dolasetron, ondansetron and tropisetron are already available). It is approved for the prevention and treatment of nausea and vomiting due to cytotoxic drugs or surgery. Although it is approved for prevention, there are limited data to support the use of granisetron in the treatment of nausea and vomiting due to radiotherapy.
Chemotherapy releases serotonin from the gut and this results in stimulation of vagal nerve terminals and the chemoreceptor trigger zone. Granisetron acts by antagonising the peripheral and central 5HT3 receptors (see 'Serotonin receptor agonists and antagonists' Aust Prescr 1991;14:46-51).
Granisetron is diluted then infused over five minutes, shortly before the cytotoxic therapy is given. A 3 mg dose will prevent vomiting in 50-70% of adult patients given cisplatin. If this preventive regimen does not work, the infusion may be repeated twice in 24 hours. The addition of a corticosteroid increases the effectiveness of granisetron.
To prevent postoperative nausea and vomiting in adults, 1 mg is slowly injected before the anaesthetic is given. A single dose is also effective in treating established postoperative nausea and vomiting.
The tablets can be given before chemotherapy and then continued for up to one week. This formulation has a bioavailability of 60% with peak plasma concentrations being reached two hours after a dose. The half-life of granisetron is approximately nine hours with most of the drug being metabolised by the liver. No dosage adjustment is recommended for patients with hepatic or renal impairment.
Headache is the most frequent adverse reaction, but patients may also complain of constipation or sleepiness. Granisetron promotes liver cancer in rats, but the clinical significance is uncertain. Altered liver function has been reported in humans.
Serotonin antagonists may be no more effective than a regimen of metoclopramide and dexamethasone, but they are usually easier to give. Practitioners will now have to decide whether to prescribe dolasetron, ondansetron, tropisetron or granisetron. The drugs appear to be similar in effectiveness, so the choice of treatment may be influenced by its price.