Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

Abstract

Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (7%) and headache (1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs, including dexamethasone and/or aprepitant, are needed to confirm the place of transdermal granisetron in the control of chemotherapy-induced nausea and vomiting.

Nausea and Vomiting in Cancer Patients: Topic Review

“…Efficacy and tolerability of transdermal granisetron for the control of CINV associated with moderately and highly emetogenic multi-day chemotherapy have been evaluated in a randomized, double blind, phase III study. The results showed that granisetron transdermal is as effective as oral granisetron [40][41][42].…”

Management of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Multiple-Day Highly or Moderately Emetogenic Chemotherapy: Role of Transdermal Granisetron

“…A total of 12% of granisetron is excreted unchanged in urine. The rest is excreted as metabolites: 49% by the urine and 34% by the feces [6,11]. Mean plasma clearance (0.79 l/kg/h in healthy subjects) is not affected by age, gender or renal function.…”

Granisetron Transdermal System in the Management of Chemotherapy-Induced Nausea and Vomiting

“…This type of CINV is a conditional or learned response. 10,11 The incidence of anticipatory CINV has reduced as antiemetic treatment advanced. Behavioral therapeutic approach should be preferable to pharmacological interventions.…”

“…General mechanisms of CINV have been elaborated in a number of reviews. 9,11 This section provides a brief overview of these reviews.…”