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

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.