Comparison of Fentanyl Oral and Nasal Formulations #331

Background

Transmucosal fentanyl formulations are available through a variety of nontraditional routes (e.g., buccal, intranasal, and sublingual). They are FDA approved for breakthrough cancer pain in patients ≥16 years of age who are tolerant of ≥60 mg of oral morphine equivalents per day.^1–7 Off-label uses include noncancer pain and painful procedures in children.^8–10 This Fact Fact compares the catalog of oral/nasal fentanyl preparations. Fast Fact #103 has more information on fentanyl lozenges (Actiq^®).

Pharmacology

Fentanyl's marked lipophilicity and high rate of first pass metabolism render traditional oral pill formulations relatively ineffective.^1–7 Yet, these same pharmacological properties lead to a quicker onset and duration of action for transmucosal or intranasal fentanyl than other short acting oral opioids (e.g., morphine, hydromorphone, and oxycodone). Hence, they may have theoretical advantages for short onset, incident pain such as cancer-related bone pain elicited by ambulation. Metabolism takes place in the liver primarily by CYP 3A4 to inactive metabolites, which are excreted by the kidneys. Significant drug interactions can occur when used with other CYP 3A4 active drugs. In those with impaired liver function, many experts recommend to initiate at 50% of the typical starting dose.

Comparative Effectiveness

In comparison with traditional oral short acting opioids, transmucosal fentanyl formulations are 20–200 times more expensive. Hence, most insurances do not cover them as first-line analgesics. Instead, they are considered if the first-line analgesic is not tolerated because of adverse effects, route issues, or an inability to control the rapid onset of breakthrough pain. A meta-analysis for breakthrough cancer pain found a likelihood of superiority over immediate release oral morphine ranging between 57% and 68%, especially during the first 30 minutes of treatment. ¹¹ However, other controlled, clinical studies not included in this meta-analysis have yielded mixed results.^9–18

Formulations

There is no known evidence clearly demonstrating superiority among the short acting fentanyl formulations; rather selection is primarily dependent on cost, preference, and insurance coverage.^1–7 Other prescribing pearls are summarized in Table 1 and also include:

• Transmucosal absorption can result in variable bioavailability depending on the formulation and the individual ingesting it. Hence, there is little dose reliability between formulations.

Patient Counseling

Patients need specific instructions regarding the following.