Joshua Murdock, PharmD, BCBBS | Director of Market Intelligence, RXinsider

Formulary decisions have always been complicated to make. They haven’t always been difficult to execute. Therapeutic interchanges, utilization management, and rebate-driven preference changes are long-standing practices, but the pharmacy end of a switch has historically been limited to a claim being rejected, a request to a prescriber to confirm an alternative, and a technician pulling a different stock bottle.

An increasing share of products moving on and off formularies are now unit-of-use items rather than traditional tablets and capsules. Unit-of-use, in this context, refers to any medication dispensed in a manufacturer’s sealed package rather than counted from bulk stock. That includes syringes, autoinjectors, single-dose vials, boxed specialty presentations, and original-container tablets. Many of these require refrigeration, and several of those carry a room-temperature window that can not be reversed once it starts. And each strength is a separate item to stock, with patients moving through several over a matter of weeks.

A single exclusion can now generate rejected claims, prescriber outreach, replacement sourcing, return or credit inquiries, and a reassessment of refrigerated inventory. How much of that lands varies with a pharmacy’s purchasing model, payer mix, and fulfillment options. The coverage decision looks the same on paper. The work it creates in the pharmacy does not, and that execution layer is the part automation is now being asked to absorb.

Exclusion lists have gotten longer, and formulary changes increasingly occur outside the annual reset

Formulary exclusion has moved from an occasional tool to a standing feature of benefit design.

Drug Channels, which has tracked the lists since 2012, counted roughly 417 products excluded by CVS Caremark in 2021, 450 by Express Scripts, and 476 by Optum Rx. About 5 years later, each of those lists carries more than 600 products.

A long exclusion list doesn’t automatically mean more work, as it may include specialty drugs that a typical pharmacy doesn’t carry. The real problem stems from a mix of issues. Higher exclusion counts increase the likelihood of encountering restricted drugs, while off-cycle changes disrupt planning. What’s more, the medications involved are often more difficult and costly to manage.

Weight management is the clearest current example. For instance, CVS Caremark removed tirzepatide (Zepbound) from certain commercial template formularies effective July 1, 2025, preferring semaglutide (Wegovy) as its glucagon-like peptide-1 (GLP-1) agonist for weight management. It has since announced that tirzepatide will return to preferred status effective October 1, 2026. Separately, it lifted its new-to-market block on orforglipron (Foundayo), an oral GLP-1, effective June 1, 2026.

Those are different kinds of formulary action, and “no longer blocked” is not the same status as “preferred.” Together, they show how quickly a preferred-product pathway can move outside the January reset.

Health plans and PBMs may issue advance notices about these changes, and prescriber offices and pharmacies may see payer messaging or claim edits before a change takes effect. But what rarely arrives is a list of which patients are affected and when their next fill is due. Without that, changes become visible one prescription at a time when a refill adjudicates differently from the previous month.

That gap is partly a technology question. Unit-of-use storage that ties into the pharmacy management system reports its own contents, so identifying affected stock becomes a lookup rather than a report to run and a shelf-by-shelf, refrigerator-by-refrigerator hunt. The same link narrows the patient side, since the system already knows which product each patient is using and when they’re due next.

The GLP-1 sequence is an inventory problem, too

Weight management was a relatively marginal pharmacy category in the mid-2010s. Once-weekly GLP-1 agonists changed that.

The FDA approved semaglutide for Type 2 diabetes in December 2017 (Ozempic) and for chronic weight management in June 2021 (Wegovy). Tirzepatide followed a similar path, reaching Type 2 diabetes in May 2022 (Mounjaro) and weight management in November 2023 (Zepbound). Within 3 years, the class has become one of the largest drivers of growth in U.S. pharmacy spending.

The progression from semaglutide to tirzepatide, and now toward products such as retatrutide, is usually framed in terms of efficacy. In the pharmacy, the difference shows up in the workflow. These products move through nearly every normal step, including receipt, data entry, adjudication, verification, labeling, will-call, and counseling. They skip one step, and it happens to be the automated one, where equipment normally counts doses and fills vials. What often replaces it is manual work related to cold-chain handling, item-level inventory control, and patient communication.

Semaglutide- and tirzepatide-based products now compete for many of the same patients, formulary positions, refrigerated inventory locations, and pharmacy workflow resources. But they are not interchangeable. A switch between them looks like a substitution at first glance, but it can behave more like a restart.

That switch is not a one-for-one exchange on the shelf. Wegovy is available in multiple injectable formulations, including single-dose pens and syringes, as well as the FlexTouch multi-dose pen. Zepbound is available in several forms, including single-dose pens and vials, as well as multi-dose vials and KwikPens. Each strength of each formulation is a separate NDC to keep in stock.

Dosing adds another layer. No universal dose-equivalence standard exists between the two medications, so the prescriber has to determine an appropriate starting dose for the replacement. That can interrupt a titration schedule and add outreach, clinical review, and dispensing work on top of the inventory change.

More is coming. Retatrutide, a once-weekly injectable triple hormone receptor agonist from Eli Lilly, cleared phase 3 in May 2026 with additional readouts pending. If approved and broadly covered, it would add a third high-demand product to an already crowded category. Additional GLP-1s will likely follow in retatrutide’s footsteps.

Oral GLP-1 formulations change the storage math

The newest entries in the class run the other way. The FDA approved oral semaglutide for chronic weight management, marketed as the Wegovy pill, in December 2025, and Foundayo in April 2026. Oral semaglutide itself is not new to the pharmacy, having been dispensed for Type 2 diabetes since 2019, but an oral option positioned against the injections changes what the weight management category asks of a pharmacy. The Wegovy pill comes in 4 strengths, and Foundayo is available in 6.

For a pharmacy that has spent the past several years rearranging refrigeration around pen inventory, an ambient option in the same class changes the requirements. These products sit on ordinary shelving, do not require cold-chain handling, and carry no device counseling requirement.

What they don’t automatically do is return the category to bulk counting. Packaging requirements are product-specific, and when a product is dispensed in the manufacturer’s container rather than repackaged, that container is technically the dispensing unit. It is a unit-of-use product for ambient storage. And multiple strengths and titration schedules mean more line items to stock.

A similar shift is underway in other therapeutic areas

Unit-of-use dispensing is not confined to Type 2 diabetes and weight management. And across several disease states, medications once administered in a clinic are now being dispensed by pharmacies instead. Many of these products move through specialty channels rather than retail pharmacies, but they show where the pattern is heading.

Neurology is one example, with lecanemab (Leqembi Iqlik) being a clear case in Alzheimer’s disease. The FDA approved a weekly subcutaneous autoinjector for maintenance dosing in August 2025, which patients could switch to after completing 18 months of IV therapy. The FDA went on to approve a subcutaneous initiation dose in July 2026, allowing at-home dosing throughout treatment. Both doses are distributed through specialty pharmacies.

That distribution channel is worth noting. A therapy that once required an infusion appointment now reaches a patient’s home refrigerator through a pharmacy, but that pharmacy is a specialty one, with its own onboarding, monitoring, and payer controls.

Oncology follows a similar path, with a growing number of oral medications reducing the historical reliance on clinic-administered infusions. For instance, the FDA approved vepdegestrant (Veppanu) for a specific type of advanced breast cancer in May 2026 and daraxonrasib (Rasonque) for metastatic pancreatic cancer in August 2026. Countless others are also available.

Tablets like these would seem to land back in familiar territory, but they rarely do. Veppanu is supplied in bottles of 30 at a once-daily dose, which is a month of treatment in the manufacturer’s container. Oral oncolytics are typically dispensed that way rather than counted into a pharmacy vial, making the original package another form of unit-of-use dispensing.

Both cases converge on the same result. A sealed manufacturer package arrives, gets verified, labeled, and stored to its label, then goes to the patient.

The drug development pipeline suggests the pattern will continue. IQVIA projects 50 to 55 new medicines launching annually through 2030, concentrated in diabetes, obesity, neurology, oncology, and immunology.

Where pharmacy automation fits into the equation

Pharmacy automation is often oversimplified to counting and packaging. A sealed manufacturer package skips that step, so these products can look like a dead end for automation. They aren’t. Counting and packaging are a fraction of what automation does.

Unit-of-use therapies require a different set of controls, including precise cold-chain maintenance, barcode verification for patient safety, and detailed inventory tracking. As these products become more common, the technology that manages their logistics matters as much to pharmacy operations as traditional dispensing automation does.

Unit-of-use storage and retrieval systems that connect directly to the pharmacy management system matter here for a specific reason. They replace the pattern of running a report and then walking the shelves and refrigerators to find affected stock with a query against a system that already knows what is on hand and where it is.

Paying for new equipment can be a real barrier, though. For instance, independent pharmacies averaged 67,601 prescriptions per store in 2024, according to the National Community Pharmacists Association, and the same dataset reported a 10-year high in the cost of goods and a 10-year low in gross profits, citing high-cost, high-volume prescriptions such as GLP-1 agonists among the contributing factors. Researchers at the USC Schaeffer Center found that nearly 1 in 3 retail pharmacies operating between 2010 and 2021 had closed by the end of that period. These are not the conditions in which pharmacies write checks for robotics.

Centralized fulfillment changes who can afford the answer

One store’s unit-of-use volume rarely justifies refrigerated automation, item-level tracking hardware, or the floor space either one requires. Aggregating volume across sites changes that.

DEA rules have permitted a central fill pharmacy to fill prescriptions on behalf of a retail pharmacy since 2003, under either a contractual relationship or common ownership, with states setting additional terms. For a health system with multiple outpatient sites, or an owner with several stores, centralizing can put enough unit-of-use volume in one place to support equipment and processes that no individual store could carry alone.

Centralizing also concentrates the work where the data already is. A facility handling refrigerated and ambient unit-of-use products for a group of pharmacies can consolidate cold-chain monitoring, item-level inventory, and return-eligibility tracking into a single system, rather than replicating all three at every location.

Looking forward: Catching the change before the claim rejects

The costliest version of a formulary change is the one a pharmacy encounters at the counter. By that point, the patient is waiting, the prescription is not ready, and the prescriber call has not started.

Most of the material needed to move that discovery earlier already sits in the pharmacy management system. A published effective date, matched against active prescriptions and refill-due dates, flags which patients are likely affected before the first claim is rejected. The same match shows which on-hand units will stop moving while there is still time to return them or work them down, and how much refrigerated capacity the replacement will need.

That match produces a candidate list rather than a definitive one. Exclusions apply at the client-plan level, and a pharmacy’s dispensing record holds the BIN, PCN, and group, not the benefit design behind them. Even so, a short list of likely-affected patients sorted by refill date is the difference between working a queue and working a counter.

Whether a pharmacy can run that match at all depends on how current its inventory record is, and that currency is built rather than assumed. The tools described earlier are what keep the record close enough to the shelf to act on, and centralized fulfillment consolidates them into one operation.

Where that process exists, a formulary change becomes a scheduled event with a known date. Where it does not, it remains an exception, surfacing one prescription at a time.

The bottom line

Formulary management is evolving. Exclusion lists are longer and more volatile during the plan year, and the products moving on and off them are increasingly unit-of-use rather than bulk. GLP-1 agonists are the clearest current example.

Those two trends amplify one another. A midyear exclusion on a solid oral generic is a claim edit and a shelf adjustment. The same exclusion on a refrigerated pen is a returns question, a cold storage reallocation, and a patient outreach list.

Dispensing and inventory automation do not remove that work. What they can do is separate it from the routine volume around it, so the products that need judgment and hands-on handling get the staff hours. At a single location, that separation has a ceiling. Centralizing fulfillment raises it, which is why a model scoped to today’s oral-solid volume will be judged in a few years by how much unit-of-use volume it can hold, both ambient and refrigerated. The pharmacies positioned to absorb the next change are the ones that already know what is on their shelves, in what condition, and under which coverage rules.

References

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