A Comprehensive Review of Rapid-Onset Opioids for Breakthrough Pain

Abstract

Breakthrough pain (BTP) is a transitory pain (reaching maximum severity in ∼15 minutes and lasting ∼60 minutes in patients with cancer) that occurs despite the management of chronic pain with long-term around-the-clock analgesia. BTP occurs in 33–65% of patients with chronic cancer pain and in ∼70% of patients with chronic noncancer pain. BTP has historically been managed with short-acting opioids; however, these medications have a pharmacokinetic profile that does not correlate with the sudden onset and short time to maximum severity of BTP. Interest in rapid-onset opioids to relieve BTP has therefore been growing. This comprehensive review aims to summarize the currently available clinical data for the approved rapid-onset opioids, which comprise different formulations of fentanyl, a μ-opioid receptor agonist with anaesthetic and analgesic properties. Administration routes for fentanyl in the management of BTP currently include the transmucosal and intranasal routes; an intrapulmonary formulation is also in development. The findings of this review suggest that the efficacy and safety of the approved rapid-onset opioids are comparable.

A fixed inhaled nitrous oxide/oxygen mixture as an analgesic for adult cancer patients with breakthrough pain: study protocol for a randomized controlled trial

“…Many studies on transmucosal fentanyl showed excellent breakthrough pain reduction after 15 min administration [11, 23, 30, 48]. But that means patients have to suffer for at least 15 minutes severe pain.…”

“…Furthermore, this fentanyl preparation is unavailable in China. In addition to the incompliance and adverse effects of oral immediate-release morphine, many other opioid formulations also appeared incapable of effectively relieving breakthrough pain due to their slow onset of actions (15–60 minutes) [11, 23, 30, 48]. This study intends to find a better alternative rescue medication for cancer patients with breakthrough pain in China.…”

Treatment of Tetralogy of Fallot Hypoxic Spell With Intranasal Fentanyl

“…[19][20][21][22] To date, there have been no reports of rigid chest associated with IN fentanyl administration in children or adults. [23][24][25][26][27] The implementation of a novel treatment with the benefits of IN administration may be another means of preventing the progression to more intensive medical, and potentially emergent surgical, interventions. TOF hypoxic spells that do not respond to initial maneuvers will require, if not already obtained, IV access so that additional parenteral therapies can be administered.…”

A new splice of life for the μ-opioid receptor

“…Heroin not withstanding, medicinal chemistry efforts have yielded a host of new pharmacological agents and inventive preparations to modify receptor-subtype selectivity, duration of action, speed of onset, and routes and methods of administration to treat a wide range of pain problems (21). Manipulation of the two ends of the temporal pharmacodynamic spectrum has led to the development of long-acting analogs and cutaneous patches for sustained pain control and formulations that are ultra-rapidly absorbed for the treatment of cancer breakthrough pain or battlefield wounds (22)(23)(24). Nonetheless, attempts to divorce analgesic effects from adverse effects continue to prove difficult.…”