Intermediate Strengths and Inflated Prices: The Story of Transdermal Fentanyl Patches

Transdermal Fentanyl Patches

The transdermal fentanyl system is a patch used to manage chronic pain in opioid-tolerant patients in the United States in whom ongoing opioid analgesia is required for a prolonged duration. It is especially indicated in people unable to take oral medications, including people with advanced cancer. With an estimated 66% pain prevalence in patients with advanced, metastatic, or terminal cancer, ¹ fentanyl patches fulfill a critical clinical need in minimizing pill burden and providing effective long-acting analgesia. Uncontrolled pain is beyond an inconvenience. It is associated with worse quality of life and financial hardship—related to decreased ability to work, reduced earnings, and resulting financial barriers to access and afford medical care to treat pain, resulting in a vicious cycle.^2,3

Intermediate strengths theoretically provide several advantages: a patient who needs 37.5 mcg/hr of analgesia could use a single 37.5 mcg/hr patch filled as a single prescription, instead of combining two separate patches, ordered separately as 12 and 25 mcg/hr scripts. Intermediate strengths allow precise titration for pain control, offer more safety, and decrease patient burdens (reduced incidence of skin reactions, adhesion difficulties, and incorrect dosing).

Current Costs of Fentanyl Patches

The “average retail price” and “lowest price with coupons” for one carton (five patches) for 12, 25, 50, 75, and 100 mcg/hr fentanyl patches are presented in Table 1. These data are from GoodRx, a nationally available drug comparison website that provides drug prices based on zip code of participating pharmacies. ⁴ The average retail price and lowest price with coupons for one carton of these standard strengths range from $84 to $248 and $27 to $63 range, respectively. Any individual, even those without prescription drug coverage, can use GoodRx and avail these prices at participating pharmacies.

Prices of intermediate strengths are significantly higher than that of the originally approved strengths (Table 1). For example, a patient requiring 62.5 mcg/hr of fentanyl and using coupons would pay $205 for one carton (five patches) if they bought a 62.5 mcg/hr patch, or just $63 (if they bought five patches each of 12.5 and 50 mcg/hr patches costing $31 and $32, respectively, and applied them both).

Previous work has highlighted pricing differences among different formulations (e.g., tablet vs. oral disintegrating tablet) of the same medication, even if the formulations are generic and the same strength. ⁵ For example, 30 U of metoclopramide 5 mg tablets cost $1.50, but 30 U of oral disintegrating tablet cost $113.79. ⁴

But the current data for fentantyl patches reflect even more arbitrary drug pricing, where the price of a formulation of a medication by the same manufacturer is not proportional to its strength. This phenomenon has also been noted for other opioid and symptom control medications. As an example, the 40 and 80 mg tablet formulations of extended-release oxycodone are notably more expensive than the 10 and 20 mg tablet formulations. A detailed list of other drugs with related pricing schemas are beyond the purview of this article.

Mechanisms Underlying These Price Differences

It is difficult to pinpoint the exact mechanism(s) underlying such price differences. We offer two hypotheses. First, price differences could represent simple supply/demand balance. Market economics dictate that newer, perhaps less prescribed, medications (such as the intermediate strength patches) command less volume and are more costly. In fact, at one of the authors' institutions, a large academic medical center, the intermediate strengths of the fentanyl patch were not dispensed even once in 2021 quarter 2 by the cancer pharmacy. This likely represents local knowledge that these formulations are more costly, and a conscious choice to not prescribe them. Indeed, although unconventional strengths may be rarely prescribed in clinical practice, most clinicians are unaware of cost differences. Drug manufacturer representatives and medical science liaisons may target marketing toward prescribers, under the veil of convenience, ultimately harming patients through financial toxicity.

Second, a majority of the price setting occurs at the supply chain level that consists of the drug manufacturer, wholesaler, retail pharmacy, and pharmacy benefit managers (PBMs). ³ The wholesale acquisition cost (WAC) is set by the manufacturer and is an estimate of the manufacturer's list price for a drug to wholesalers before any rebates or discounts are negotiated by the PBM on behalf of the insurer for preferred formulary placement. The WAC for transdermal fentanyl patch is shown for the same authors' institution in Table 1 and underscores remarkable differences across strengths. It notes significantly higher WAC prices for intermediate strengths of fentanyl, which may explain even higher prices being commanded further downstream even after drug rebates and discounts. Importantly, the patient's cost sharing under insurance deductibles or coinsurance is based on the list price, as is the price paid by cash paying patients. Thus, higher list prices are ultimately borne by insured and uninsured patients at the pharmacy counter.

Impact on Patients and Health Systems

Most clinicians and prescribers are unaware of this marked price discrepancy between fentanyl patch formulations. This is just one example of a drug market system unable to protect vulnerable patients already facing significant symptom, psychosocial, and financial burdens. We often think of financial toxicity with regard to brand-name drugs; however, all formulations of the fentanyl patch available today are generic, and have been predominantly generic for a long time (brand name Duragesic was discontinued by Janssen in 2020).

In clinical practice, many of us working in an academic setting with pharmacy resources and support choose to prescribe a combination of 12 and 25 mcg/hr patches instead of a 37.5 mcg/hr patch, which is more expensive than even the highest older strength (100 mcg/hr). Clinicians in less resourced settings in busy clinics may be unable to do the same. For patients who are prescribed an intermediate strength patch, this represents a preventable example of significant financial toxicity.

Proposed Solutions

Short-term institutional solutions include changing default options in the electronic medical record to include the traditional less costly strengths, or show only traditional strengths unless one actively searches for an intermediate strength. ⁶ Other potential solutions include pharmacy oversight for clinicians choosing to prescribe intermediate strengths, or real-time benefit tools displaying costs for drugs that are close substitutes for the drug being prescribed (different strength, dosage form, or other alternative drug). Similar to any workaround, these are temporary imperfect solutions.

At the PBM and employer level, implementing a waste-free formulary could provide potential savings. ⁷ As much as we discourage routine utilization management strategies (e.g., prior authorization), which reduce clinician autonomy and clinical efficiency, payer-imposed interventions may be necessary to reduce health system, and thus patient, costs.

Broadly, this issue reflects how difficult it is for even well-meaning clinicians to “do the right thing.” Longer term solutions require greater regulation and standardization of drug pricing. This includes reference pricing (based on local or international pricing indices that allows a drug purchaser to put a maximum limit on their willingness to pay for a certain drug), setting ceiling prices (maximum prices purchasers can pay for drugs), drug inflation rebates (manufacturers rebate to Medicare the amount that drugs rise above the rate of inflation), greater price transparency between list and net price, and greater drug price negotiation on part of the federal government (such as Medicare), similar to what is already done by the Department of Veteran Affairs and the Department of Defense, or a large private insurer such as the Kaiser Health System.

Conclusions

Although intermediate strengths of the transdermal fentanyl patch may appear to provide greater convenience to patients and flexibility to providers, a complex and opaque drug pricing system prevents their most notable benefits from being realized. For patients with advanced cancer, significant pain, and fragile skin facing financial distress, perhaps the best solution—if we are unable to control the price—is to remove the unconventional strengths altogether from the market.

Funding Information

No funding was received for this article.