New Drugs and Devices From 2011 – 2012 That Might Change Your Practice

Joe Lex, MD


Western J Emerg Med. 2013;14(6):619-628. 

In This Article

Subsys® (Fentanyl Sublingual Spray Formulation for Breakthrough Cancer Pain)

Fentanyl is, of course, an opioid agonist with many indications for pain treatment. It is approximately 100 times more potent than morphine, with 100 micrograms of fentanyl approximately equivalent to 10 mg of morphine in analgesic activity. It is highly lipophilic and easily penetrates the bloodbrain barrier. This sublingual spray formulation is indicated only for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain.

Fentanyl was derived from metabolites of meperidine (pethidine) in 1960 by Paul Adriaan Jan, Baron Janssen, founder of Janssen Pharmaceutica. The highly prolific baron also discovered haloperidol (1958), droperidol, and etomidate, as well as diphenoxylate, the primary ingredient in the antidiarrheal medication, Lomotil.

Fentanyl has been used for widespread palliative use since the 1990s. First on the market was the transdermal Duragesic® patch, followed by first quick-acting fentanyl formations in a transmucosal formulation, the Actiq® lollipop and Fentora® buccal tablets. Even the U.S. military is looking at transmucosal fentanyl for battlefield treatment of pain. Sublingual spray is a logical extension of these other delivery systems. Derivatives of fentanyl have also been developed for specific purposes: there is a summary of these derivatives in Table 7.

Fentanyl is currently considered one of the safest opioids on the market, and the least physically harmful to the body, especially with long-term or life-term use. Its therapeutic index is 270:1. Fentanyl's major side effects (>10% of patients) include diarrhea, nausea, constipation, dry mouth, somnolence, confusion, weakness, and sweating. Despite it being a more potent analgesic, fentanyl tends to induce less nausea and less histamine-mediated itching in relation to morphine.

Healthcare professionals who prescribe Subsys® on an outpatient basis must first enroll in the Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy TIRF REMS ACCESS program (see and comply with the requirements of the REMS to ensure safe use of SUBSYS. As with all opioids, the safety of patients using such products is dependent on healthcare professionals prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use. While you will probably not prescribe Subsys®, you will almost certainly see patients who take it.