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12 Articles in Volume 21, Issue #2
Advanced Practice Matters with Theresa & Jeremy: MAT and the DATA Waiver Debate
Analgesics of the Future: The Potential of Vocacapsaicin Injections for Knee Pain
Authorities Update Opioid and Naloxone Prescribing Policies as Overdoses Soar
Autologous Adipose-Derived Biocellular (Stem Cell-Rich) Prolotherapy into Hoffa’s Fat Pad Improves Knee Osteoarthritis
Behavioral Medicine: How to Utilize Acceptance and Commitment Therapy in Primary Care
Case Report: How We Grew Our Pain Practice Amidst Pandemic, Opioid Crisis
Chronic Overlapping Pelvic Pain Disorders: Differential Diagnoses and Treatment
Fentanyl Transdermal Patch: Variability is Key When Prescribing
Optimizing Opioid Therapy with Pharmacogenetics
Research Insights: Advances in Shoulder Arthroplasty and Revision Surgery
Research Insights: How to Address Osteoarthritis Treatment Gaps in Women
Topical Anti-Inflammatories: Analgesic Options for Arthritis Beyond NSAIDs

Fentanyl Transdermal Patch: Variability is Key When Prescribing

When treating pain with a fentanyl transdermal patch, clinicians need to consider the wide variability in opioid conversion calculations, potency, and shifting medical requirements to avoid potential adverse events.

The fentanyl transdermal patch is a unique formulation that utilizes a transdermal system for providing sustained action with a short-acting medication such as fentanyl. This mechanism allows for the treatment of pain in opioid-tolerant individuals with stable chronic pain who require long-term analgesic therapy with an opioid.

When used appropriately, the patch is an effective and convenient option for patients with severe, chronic pain who cannot take daily oral medications and who need prolonged opioid treatments.1,2 The patch is designed to transfer high doses of fentanyl via transdermal delivery at constant rates of 12.5, 25, 50, 75, and 100 µg h-1 for a total of 72 hours.The delivery system of this patch is associated with delayed onset and prolonged duration of action, which compromises flexibility in dose titration and may result in adverse opioid side effects. Physicians who prescribe these patches play a critical role in ensuring that the medication is appropriately and safely administered to patients.

Physicians’ incomplete knowledge of transdermal fentanyl can be a source leading to potential error. From responses to a prescribing survey on opioid conversion calculations, Rennick et al found inconsistency and wide variability in opioid conversion calculations; an “alarming” result was for differences in conversions for fentanyl. Rennick’s team suggested that this may be a reflection of “overconfidence in equianalgesic tables, source inconsistency, and reliance on personal knowledge.”3

In a retrospective cohort study on the initiation of transdermal fentanyl, Constantino et al found that a large percentage (84%) of patients who were initiated on this medication did not meet the criteria for opioid tolerance derived from the FDA package insert; most patients failed to meet the time-exposure requirement.4 The authors also expressed concern that several  patients were converted to transdermal fentanyl after having only received tramadol.

Despite recommendations and safety warnings provided by ISMP and the FDA, fentanyl transdermal patches are still being used inappropriately (iStock).

Common Themes in Adverse Events Using Fentanyl Skin Patches

Numerous case reports of adverse events (AEs) with fentanyl transdermal patches − including fatalities − caused by inappropriate prescribing, dispensing, and administration of the drug have appeared in several editions of Institute of Safe Medication Practices (ISMP) newsletters,5 including a 2020 article focused on a long-term care pharmacy that reported the rise in inappropriate prescribing of fentanyl transdermal patches for opioid naïve patients and to treat acute pain. 

Despite recommendations and safety warnings provided by ISMP and the FDA, fentanyl transdermal patches are still being used inappropriately. Lack of knowledge regarding differences in potency is one of the reasons given by the Joint Commission for the common implication of opioids in AEs.6

A 2017 analysis released by the Institute for Safe Medication Practices Canada found several recurring themes in cases involving patients who died or experienced unwanted side effects from complications with the fentanyl transdermal patch:

  • “There was unclear communication and lack of understanding among patients/caregivers/other health care professionals in regard to patient-specific dosing interval (eg, every 72 hours versus every 48 hours) for fentanyl transdermal administration.
  • Lack of standardized fentanyl guidelines for prescribers to clearly specify the correct quantity (ie, number of patches), strength, and dosing interval and to assess patient’s opioid-tolerability and contraindications including any concurrent use of other maintenance and/or breakthrough pain medications.
  • Lack of a drug/drug interaction (DDI) alert system in place to remind the prescriber for potential DDI and/or other contraindications.
  • Lack of knowledge or awareness of the indication for the use of fentanyl patches.
  • Contraindicated in the management of postoperative pain, mild pain, or intermittent pain (eg, use “as needed”) because of the risk for serious or life-threatening respiratory depression.
  • Only prescribe a fentanyl patch of 25 mcg/hour if the patient has been receiving the equivalent of at least 60 mg of oral morphine per day for an extended period.
  • Incorrect calculation of “morphine equivalents” total daily dose.
  • Over-estimating the dose when doing fentanyl dose adjustment or converting from another opioid.
  • Lack of standardized prescribing fentanyl guidelines to include an equianalgesic conversion table as reference for prescribers”.7


The Fentanyl Patch and Opioid “Equivalents”

A retrospective study examining patterns of opioid use at admission to a Belgian palliative care unit found that there is a lack of knowledge regarding dose equivalence of opioids. Patients were equally divided into those who received morphine and those who received transdermal fentanyl. However, the median dose of those on the fentanyl transdermal patch (180 mg oral morphine equivalent (OME) was triple that of those receiving oral or parenteral morphine (60 mg OME).

These differences were not explained by the fact that the patients on fentanyl were suffering from more pain. The authors noted that doctors “do not always appreciate the dose equivalence of the fentanyl patches and may on some occasions be using the drug inappropriately and at much higher doses than they would use when they were prescribing oral or parenteral morphine.”8 (More on fentanyl: fact versus fiction.)

Research promotes morphine-equivalent daily dose (MEDD) to justify transitioning from a currently prescribed opioid to one or more opioid “equivalents.” However, Fudin et al, explained that most guideline recommendations are supported only by single-dose studies, observational data, or expert recommendations without consensus as to what actually constitutes a “morphine equivalent.” In addition, physicians must be able to understand and apply conversion information differently for each case to account for patient-specific factors such as “pharmacogenetics, organ dysfunction, overall pain control, drug tolerance, drug-drug interactions, drug-food interactions, patient age, and body surface area.” 9

Reliance on product labeling and practitioner education alone is insufficient to solve this potentially life-threatening misuse of the fentanyl transdermal patch. In 2007, the ISMP recommended health care settings (hospitals, physician offices, and ambulatory surgery centers) create guidelines for the safe use of the fentanyl patch.5

Potential for Confusion over Medical Requirements for Prescribing Fentanyl

There is the potential for confusion in the medical requirements specific to the prescribing of sustained-release opioids. This confusion may impact the evaluation of the conditions which must be met to adhere to guidelines for safe prescribing for pain:

  • that cannot be controlled by other means
  • that requires at least 60 mg of oral morphine daily or equivalent,
  • that requires long-term pain control, and
  • for which the patient has received routine opioid therapy in the previous 7 days.

The Opioid-Naïve Patient

For instance, an opioid-naïve patient may require high doses of an opioid for longer than a week’s duration. In this case, the criteria for “opioid tolerance” would be reached. The manufacturer identifies that opioid tolerance can be reached in a week and thus a fentanyl transdermal patch would be appropriate. However, this same patient would still be considered to be experiencing acute pain. It is unclear if this patient meets the criterion of “requires long-term pain control.”

A prescriber may or may not conclude that “long-term” refers to a 3 to 6 month period identified for chronic pain.10 In addition, the guidance to fulfill the four conditions (see above) overlaps with medical judgment; medical judgment involves interpretations of the information available.In the service of efficiency, physicians may neglect to review the chart, and instead rely on their own clinical judgment, which may be inconsistent with prescribing guidelines.

Physician Autonomy in Overriding Fentanyl Prescribing Guidelines and Alerts

At one time, physicians were not receptive to practice guidelines and algorithms, despite the evidence supporting this type of guidance and decision support for opioid prescribing. This view shifted to more rigid compliance of guidelines following an epidemic of opioid overuse and the publication of the CDC Guideline for Prescribing Opioids for Chronic Pain.11 There are various clinical settings in which prompts and alerts have been studied, including primary care,12 emergency departments,13 and hospital settings.14 Alert systems attempt to influence physician decision making. The majority of unpublished reports describe prescribing systems that prompt the physician with warnings about specific error possibilities such as dose recommendations, drug interactions, reminders of disease conditions, laboratory results, and allergies. However, there is a lack of research available that examined for alert systems regarding medical indications.15

The incidence of physicians overriding these prompts and alerts is significant. Reasons given for overrides include:

  1. patient tolerated medication in the past
  2. the medication is administered for short-term use only
  3. alert not clinically significant
  4. benefit outweighs disadvantages.12

It is of interest that few of the ignored alerts resulted in patient AEs. The authors cite that 99.9% (4,563/4,559) of overridden alerts were not associated with an actual adverse drug event,16 further strengthening the prescribers’ confidence in the validity of overriding the warning and contributing to alert fatigue. This suggests that the alert thresholds are set too low, explaining the excessive false-positive alerts.17 It is logical to conclude that physician-friendly alert systems need improvement.18

Additionally, a medical indication alert system treads on the sensitive area that threatens a physician’s sense of autonomy and virtuosity. It is also likely that the prescriber may ignore the alerts in the interest of efficiency or alert fatigue. The decision to initiate a therapy requires more complexity in a decision support system that goes beyond simple alerts.

Using EHRs and PDMPs to Support Clinical Decisions When Prescribing Fentanyl

As EHRs became more sophisticated, there have been many attempts to integrate the tools and guidelines intended to aid the physicians in clinical decision support (CDS) when prescribing opioids, including the fentanyl transdermal patch. Most EHRs in healthcare settings have implemented the recommendation that prescribers must “acknowledge” that the patient meets the four conditions noted above for the safe use of fentanyl patches. Also, the patient’s current opioids use and pain assessment are grouped under “pain management” for their review. Upon processing a fentanyl patch order, pharmacists are required to review and verify that the patient is opioid-tolerant and has chronic pain before approving the prescription.  (More on chronic opioid therapy and symptom management.)

Some of the major EHR systems in the United States have incorporated the link to the Prescription Drug Monitoring Program (PDMP) directly within their EHRs’ workflow so that both the prescribers and pharmacists can review the history and analyze prescription fill patterns of patients in a more comprehensive way while ordering and verifying orders, respectively. This tool provides an additional opportunity for the prescribers to screen for and discuss concerns about addiction or diversion with patients.

Another commonly incorporated feature in the EHRs is the “opioid safety toolkit” with access to the opioid conversion table and the standardized opioid treatment agreement.19 For example, the opioid conversion table from the CDC is a comprehensive resource for primary care providers treating chronic pain that can be managed with  50 MME (morphine milligram equivalent)/day as an initial recommendation. These are “not intended for active cancer, palliative, and end of life care.”20

The CDS features should always be reviewed and validated by the organization that mandates the EHR in use by their providers. In some cases, the CDS features can be misleading and biased intentionally favoring the prescribing of certain products. For example, in a recent legal case, an EHR company paid a large penalty in an opioid kickback scheme.21 The other tool, the opioid treatment agreement, is to be used with patients to help prevent addiction and increase communication between patients and their providers.

The availability of the aforementioned CDS in the EHRs is not widespread, however. Possible reasons include: the request for such access depends on the need of the users (primary care, hospitals, palliative care, or emergency department settings) and there are many opioid conversion tables easily accessible on the Internet. The embedded CDS tables or links often are not obvious to the user, take multiple clicks to get to them, and require repeated in-service of their availability as clinician turnover occurs.  

Practical Takeaways

In conclusion, confusion over medical requirements, physician autonomy, and task burden have all been shown to impact the physician decision-making and variability of fentanyl transdermal patch prescribing. Clinicians must recognize that there is a considerable amount of confusion about fentanyl patch use. Exercising the best medication safety practices when prescribing, verifying, documenting, and dispensing that consider the patient’s opioid status and types of pain cannot be over-emphasized.

There is a wide variation of computerized alerts and prompts. Although some may cause alert fatigue, they are to protect providers against potential prescribing errors or support them in their prescribing decisions. They are derived from the practice guidelines and recommendations for a safe prescribing for opioids including fentanyl patches. Physician autonomy in overriding them may be justified if they are accompanied by cautious assessment of the patient characteristics, opioid status, and type of pain.

Finally, EHRs can offer access to multiple resources for automatic review and calculations for the clinicians in prescribing the fentanyl transdermal patch and reduce errors. The adaptation and incorporation of such resources, however, should be done with caution and thorough evaluation of the available, unbiased, resources. Clinicians need to realize that the published equianalgesic ratios are only crude estimates at best and cannot account for an individual patient’s genetics and pharmacokinetics. Therefore, it is imperative that careful consideration is given to individualizing the dose of the selected opioids, especially when prescribing the fentanyl transdermal patch.

Last updated on: March 2, 2021
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