Intranasal fentanyl spray for breakthrough cancer pain: An innovative approach to the unmet needs

The treatment of breakthrough pain (BTP) in cancer patients is often sub-optimal. Normal-release oral opioid formulations have a slow onset of action, such that the episode of pain has often spontaneously subsided by the time the opioid starts to work. Other oral formulations, such as oral transmucosal fentanyl citrate (OTFC), may be associated with administration problems in many cancer patients who have salivary gland dysfunction or mucositis. Thus, there is the need for a treatment that matches a typical BTP episode and that is easy to use. Intranasal fentanyl spray (INFS) has been developed as a new route of administration with a fast onset of action. INFS has been investigated in four key clinical studies involving cancer patients with BTP. Pharmacokinetic analysis has shown a dose response for maximal plasma concentrations (Cmax) of fentanyl and a short venous time to maximum plasma concentration (Tmax). A dose-ranging efficacy study demonstrated a significant improvement in pain intensity difference (PID) over placebo from as early as 10 min post-administration. A later titrated-dose efficacy study supported these findings. In a head-to-head comparative trial between INFS and OTFC, significantly more patients achieved a faster onset of 'meaningful' pain relief with INFS than with OTFC, with INFS producing a significantly greater PID as early as 5 min post-dosing. Furthermore, a significantly higher proportion of patients preferred INFS over OTFC. In all clinical studies, including a 10-month follow-up, INFS was well tolerated. INFS should be considered a significant advance for the management of BTP.