A pharmacokinetic assessment of an alternate titration strategy for fentanyl pectin nasal spray.

ABSTRACT

OBJECTIVE: Fentanyl pectin nasal spray (FPNS) is approved for management of breakthrough pain in cancer. It is available in 100 and 400 µg strength products which allow for doses of 100 - 800 µg (1 or 2 sprays). Existing titration strategies require a transition from the 100 µg product to the 400 µg product when increasing the dose from 200 to 400 µg. This study assessed the pharmacokinetic (PK) profile of FPNS administered as 4 sprays of 100 µg as an alternate titration strategy. METHODS: In this 3-way, crossover study, healthy subjects aged 18 - 65 years were randomized to receive each of 3 dosages of FPNS (4 × 100 µg, 2 × 100 µg, and 1 × 400 µg). PK samples were collected over 24 hours. RESULTS: Of 22 subjects randomized, 20 were included in the PK analysis. Administration of both 400 µg regimens (4 × 100 µg and 1 × 400 µg) provided greater systemic fentanyl exposure compared with the 200 µg dose (C(max) 1,748 and 1,485 pg/ml vs. 1,051 pg/ml; AUC(0-1h) 1,012 and 944 pg×h/ml vs. 665 pg×h/ml; and tmax 0.25 hours and 0.50 hours vs. 0.25 hours); fentanyl exposure after 4 × 100 µg and 1 × 400 µg regimens was similar. Adverse events (AEs) were all mild or moderate in intensity; most common AEs were nausea (50%) and headache (23%). AE frequency was similar across treatments without reports of nasal effects. CONCLUSIONS: Given that systemic fentanyl exposure from FPNS administered as 4 × 100 µg is similar to that from FPNS as 1 × 400 µg, the 4 × 100 µg regimen provides an alternate titration strategy for patients needing more than 200 µg. This alternate strategy will facilitate a patient's ability to achieve an optimized FPNS regimen and reduce opioid wastage.