Single-dose fentanyl sublingual spray for breakthrough cancer pain

Abstract

Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60–90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.

Formulation and evaluation of sublingual delivery of piroxicam using thermosensitive polymer with an inverted Franz diffusion cell

“…It can be inferred from the observed values that the sublingual tissue offers the least resistance for the drug to permeate. This may be one of the reasons why sublingually administered drugs such as fentanyl citrate, buprenorphine, nitroglycerin, isosorbide dinitrate, and nifedipine reach a higher therapeutic level within few minutes after sublingual administration . The resistance values of the tested sublingual tissue are given in Table .…”

Cost-Effectiveness Analysis of Oral Fentanyl Formulations for Breakthrough Cancer Pain Treatment

“…The use of sublingual or oral administration instead of the intra-nasal is related to other aspects than only the lowering pain intensity. Some patients could have contraindication of intra-nasal formulation, other patients can prefer the sublingual or oral administration instead of the intra-nasal and some patients can have a problem in the use of the device for intra-nasal formulation [19,25,40]. These aspects are really difficult to include in a cost-effectiveness model.…”

“…The specific health care resources used and the associated costs for each formulation were retrieved from a recent budget impact analysis [19]. The health care resources consumption was estimated based on the average health care resources consumed by patients treated with fentanyl formulation reported in the Budget Impact Analysis (BIA), and based on a linear relationship between health care consumption and time to analgesic onset reported for each formulation [18,25,28]. The Public Price (PP) was considered to quantify the cost of drugs used [35] and was reported in Table 3.…”

Sublingual spray: a new technology oriented formulation with multiple benefits

“…In summary, rapid onset of analgesia can be produced and justiied by fentanyl sublingual spray that strives as an effective treatment for cancer pain. (Taylor, 2013).…”