“Transdermal buprenorphine and fentanyl have been found to be unsatisfactory in less than 5 percent individuals”.

Though why it has been labelled as unsatisfactory has not been clearly defined, this statement might lend itself to various interpretations. Lack of efficacy (due to inconsistent plasma levels) and unsuitability underlying intolerable adverse effects are a few that come to mind. Additionally, poor quality of the patch, which allows for improper adhesion to the skin might also play a role. Fever, sarcopenia and sweating have all been shown to affect absorption.

Discontinuation is more common when TD fentanyl is used in strong opioid-naive patients. Opioid naive patients are more susceptible to the delayed onset adverse effects of transdermal fentanyl during the first 12-24 hours of the absorption phase when initiated. These adverse effects may include, but are not limited to respiratory depression and sedation. High lipophilicity allowing CNS penetration, rapid receptor association and dissociation producing higher level make TD fentanyl, a riskier option in the opioid naive.

This might underlie the recommendation for using transdermal fentanyl in opioid tolerant patients and advising increased scrutiny and close monitoring during the first 24 hours, when used in the opioid-naive.

Buprenorphine transdermal patches, despite their prohibitive costs continue to be used in opioid naive patients, for moderate pain. Its partial mu-opioid receptor agonism, ceiling effect for respiratory depression, high receptor affinity and opioid equivalent doses well within the range of those suited for use in the opioid naive contribute towards its better safety.

Caution is also to be applied prior to prescribing pure mu opioid receptor agonists in those who have been on transdermal buprenorphine as a blunting of the initial response might be observed (due to stronger affinity for receptor binding). This phenomenon might be relevant when rotation from buprenorphine to another opioid is being planned without an ample washout period. This phenomenon has been referred to as functional withdrawal. The same phenomenon underlies the cautious prescription of strong opioids for breakthrough pain along with higher doses of buprenorphine.

Reference

Wilcock, A., Howard, P., Toller, C. S., Droney, J., & Charlesworth, S. (Eds.). (2025). Palliative care formulary (9th ed.). Pharmaceutical Press.

Dahan, A., Yassen, A., Romberg, R., Sarton, E., Teppema, L., Olofsen, E., & Danhof, M. (2006). Buprenorphine induces ceiling in respiratory depression but not in analgesia. BJA: British Journal of Anaesthesia, 96(5), 627–632. https://doi.org/10.1093/bja/ael051

Wedemeyer, M. J., Chavera, T. S., Berg, K. A., & Clarke, W. P. (2025). Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium. European Journal of Pharmacology, 987, 177192. https://doi.org/10.1016/j.ejphar.2024.177192

Cite as
Arora, R. D. (2026). Palliative Pearls (PP11)- Formulary focused care – unsatisfactory response to transdermal opioid formulations. Zenodo. https://doi.org/10.5281/zenodo.20840184

Disclaimer
Palliative medicine is a relatively young subspecialty whose intellectual and clinical boundaries continue to evolve. In the absence of definitive texts to address contemporary questions, artificial intelligence tools mainly Anthropic (Claude) have been employed to support deeper conceptual exploration, challenge assumptions, and improve clarity of expression. They do not replace critical scholarship, clinical experience, or editorial judgment. Final responsibility for all interpretations, factual accuracy, originality of synthesis, and the quality of the published material rests entirely with the Founder and Editor.