Absorption of fentanyl from fentanyl buccal tablet in cancer patients with or without oral mucositis - A pilot study

Background and objectives: Patients with cancer, particularly those undergoing chemotherapy or radiotherapy, may develop oral mucositis. This is the first study to investigate the absorption profile of fentanyl buccal tablet (FBT) - an effervescent formulation of fentanyl indicated for the management of breakthrough pain in opioid-tolerant cancer patients - in patients with or without oral mucositis. Methods: In this open-label study, patients with or without oral mucositis self-administered a single 200 mu g dose of FBT by placing the tablet between the upper gum and cheek above a molar tooth. Venous blood samples for measurement of plasma fentanyl concentrations were collected at regular intervals up to 8 hours following FBT administration. Parameters of interest included maximum plasma concentration (C-max), time to reach Cmax (t(max)), area under the plasma concentration-time curve from time zero to 8 hours (AUC(8)), and AUC from time zero to the median tmax (AUC(tmax')). Adverse events were monitored throughout the study. Oral mucosal examinations and measurements of vital signs were performed at intervals up to 8 hours following FBT administration. Results: Sixteen patients, 8 with and 8 without oral mucositis, received FBT and completed the study. The severity of oral mucositis was mild in the patients exhibiting this condition. Median Cmax values were comparable: 1.14 ng/mL (range 0.26-2.69 ng/mL) in patients with mucositis, and 1.21 ng/mL (range 0.21-2.34 ng/mL) in patients without mucositis. The tmax was not significantly different in the two groups: median tmax was 25.0 min (range 15-45 min) in patients with mucositis and 22.5 min (range 10-121 min) in patients without mucositis. Median AUCtmax' values were 0.17ng center dot h/mL (range 0.04-0.52 ng center dot h/mL) in patients with mucositis, and 0.20 ng center dot h/mL (range 0.00-0.65 ng 9 h/mL) in patients without mucositis. The corresponding AUC8 values were 2.05 ng center dot h/mL (range 1.16-3.83 ng center dot h/mL) and 1.55 ng center dot h/mL (range 0.74-3.07 ng 9 h/mL), respectively. FBT was generally well tolerated in this small group. No application site adverse events or changes in oral mucosal assessments were reported. Conclusion: The absorption profile of a single dose of FBT 200 mu g was similar in patients with or without mild oral mucositis. The compound was generally well tolerated.