Intra-nasal fentanyl for breathlessness

Participants are to be randomized into 2 treatment groups with sequences composed of 2 sets of 3 administrations (number 1-3 and 4-6), with each set comprising of fentanyl 5 microgram/puff, and placebo- an inactive drug. Patients in group 1 receive fentanyl in bottles 1-3 and placebo in bottles 4-6. Patients in group 2 receive placebo in bottles 1-3 and fentanyl in bottles 4-6. Patients are instructed to treat 6 episodes of acute shortness of breath using the order the spray bottles are ordered and they are to record their response at set interval. If symptom persists after 15 minutes, they are to take their usual rescue medication. Results are then analyzed to determine efficacy and any adverse effects of the treatment. Intra-nasal fentanyl, 5mcg/puff, 2 puffs are administered into each nostril = total dose of 20mcg for each breathlessness episode. This can be repeated upto hourly. The number of episodes to be treated is six episodes per patient. This is based on pharmacokinetic study that shows therapeutic concentration is achieved within 2 minutes and elimination half -lives are found to be 29.8 and 31.2 minutes for solution pH of 6 and 8 respectively. (Lim, Sunderland et al 2003). Based on the above mentioned half-lives, the wash out period between fentanyl and placebo is 60 minutes. Adherence is based on what is reported by patients using study questionnaires that record study drug use. The questionnaires are collected and checked with patients at the final study visit. it is expected six breathlessness episodes are very readily achievable over 24 hours to 7 day period in hospice patients who have high symptom burden. Lim S, Paech MJ, Sunderland B, Roberts MJ, Banks SL, Matthew R. Pharmacokinetics of Nasal Fentanyl. Journal of Pharmacy Practice and Research. 2003;33(1):59-63