Pain-Relieving Lollipop: Transcutaneous Fentanyl for Breakthrough Cancer Pain
ABSTRACT & COMMENTARY
Synopsis: Newly FDA-approved, oral transmucosal fentanyl citrate was shown to produce significantly larger decreases in pain intensity and better pain relief than placebo in a randomized, double-blinded, placebo-controlled clinical trial.
Source: Farrar JT, et al. J Natl Cancer Inst 1998;90: 611-616.
Cancer often produces pain, especially in its later stages. The pain is generally of two types: chronic persistent pain and intermittent episodes of acute pain superimposed on the chronic persistent pain. The intermittent episodes of acute pain are often called breakthrough pain, and, according to the latest (1998) edition of the Oxford Textbook of Palliative Medicine, in 35-69% of patients the breakthrough pain is of sufficient severity to interfere with normal activity. Because the onset of the pain is often abrupt and because it appears on a background of persistent pain that is often being managed with opiates, breakthrough pain creates a serious management dilemma. Intervention needs to be swift with an agent that has a rapid action; however, the drug needs to have a sufficiently long half-life to relieve the pain and a sufficiently short half-life to prevent the development of opioid overdose symptoms like somnolence and respiratory depression. The most frequently prescribed opioids for breakthrough pain are short-acting oral agents that generally take 20 minutes or more to start working and have a peak effect in 30-45 minutes.
Enter oral transmucosal fentanyl citrate-literally a pain-relieving lollipop. About a decade ago, Stanley and colleagues in the Department of Anesthesiology at the University of Utah noticed that oral administration of fentanyl produced symptom relief in a much shorter period of time (often within 5 minutes) than would be required for gastric absorption of an oral dose. They deduced that fentanyl could be absorbed rapidly through the oral mucosa. After performing careful pharmacokinetic analysis,1 they started a company (Anesta Corp.) and began to develop fentanyl lollipops for clinical indications.
Farrar and colleagues recently published a randomized, double-blinded, placebo-controlled clinical trial among patients who were receiving at least 60 mg oral morphine or 50 mcg of transdermal fentanyl per day. Patients who developed breakthrough pain had their pain-relieving dose of oral transmucosal fentanyl determined and were then given 10 randomly ordered treatment units (7 fentanyl, 3 placebo). If a particular lollipop did not induce pain relief within 30 minutes, the treatment was considered a failure and the patient was given their standard medication for breakthrough pain. Only 15% of episodes treated with fentanyl required rescue medication compared to 34% with placebo (P < 0.0001). Pain relief was obtained. Side effects were mild and infrequent: dizziness in 17%, nausea in 14%, and somnolence in 8%.
Oral transmucosal fentanyl citrate is a safe and effective adjunct to pain management and is particularly useful in the treatment of breakthrough pain that complicates chronic persistent pain.