General Information

Sustol (granisetron) is a serotonin-3 (5-HT3) receptor antagonist.

Sustol is specifically indicated for use in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. 

Mechanism of Action

Sustol (granisetron) is a serotonin-3 (5-HT3) receptor antagonist. Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy that induces vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. This evokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to 5-HT3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin.

Side Effects

Adverse effects associated with the use of Sustol may include, but are not limited to, the following: 

• injection site reactions
• constipation
• fatigue
• headache
• diarrhea
• abdominal pain
• insomnia
• dyspepsia
• dizziness
• asthenia
• gastroesophageal reflux

Dosing/Administration

Sustol is supplied as an extended-release injection for subcutaneous use. The recommended dose in adults is 10 mg administered as a single subcutaneous injection at least 30 minutes before the start of emetogenic chemotherapy on day 1.

• Do not administer Sustol more frequently than once every seven days.
• Use of Sustol with successive emetogenic chemotherapy cycles for more than six months is not recommended.
• See full prescribing information for recommended dosage of concomitant dexamethasone.

Clinical Trial Results

The FDA approval of Sustol was based on a randomized, multicenter, double-blind, parallel group study. A single 10 mg subcutaneous dose of Sustol was compared to a single 0.25 mg intravenous dose of palonosetron hydrochloride in cancer patients administered moderately emetogenic (MEC) or anthracycline plus cyclophosphamide (AC) combination chemotherapy. Sustol or palonosetron hydrochloride was administered 30 minutes prior to chemotherapy on day 1. Patients also received either 8 or 20 mg intravenous dexamethasone on day 1 depending on chemotherapy regimen. Patients who received 20 mg of intravenous dexamethasone also received oral dexamethasone 8 mg twice daily on Days 2, 3 and 4. The primary endpoints were proportion of patients with complete response (CR) [defined as no emetic episodes (vomiting or retching) and no use of rescue medication] during the acute phase (0 to 24 hours) and the delayed phase (>24 to 120 hours) following the administration of chemotherapy in cycle 1. The study design allowed for assessment of non-inferiority of Sustol to palonosetron hydrochloride in the acute and delayed phase of MEC and of AC combination chemotherapy. Non-inferiority of Sustol to palonosetron hydrochloride was demonstrated in the acute and delayed phases of MEC and of AC combination chemotherapy.