The Alternative That Might Not Be There Next Month
A single patient whose safer prokinetic option is disappearing from the U.S. market while her doctors are still deciding whether to prescribe it. The disagreement isn't about which drug fits her — it's about how to plan around one that might not be there much longer.
Renata S., a 52-year-old bakery owner, has had type 1 diabetes since childhood and has run her own six-day-a-week business for the past eleven years — early mornings that used to start with coffee and now start with nausea she has to fight through before she can trust herself around a hot oven. Gastroparesis was confirmed on scintigraphy eight months ago after her early satiety and postprandial bloating stopped responding to dietary changes alone. A three-month metoclopramide trial helped meaningfully, but at week ten she noticed an intermittent facial tic she hadn't had before — not dramatic, but new, and enough that her endocrinologist stopped the drug immediately given metoclopramide's boxed warning for tardive dyskinesia with any use beyond twelve weeks.
Domperidone was the obvious next step — a peripheral D2 antagonist that, unlike metoclopramide, doesn't meaningfully cross the blood-brain barrier and so carries essentially no tardive dyskinesia risk, the exact profile her case now calls for. It has never been FDA-approved in the United States, available only through the FDA's compassionate-use IND pathway, because of a separate QT-prolongation signal serious enough to have kept it off the standard market for decades. That access route existed reliably for years — until this year, when the sole remaining U.S. importer notified prescribers it is exiting the business, turning what was a stable if narrow supply line into one Renata's endocrinologist can no longer promise will still be there by her next refill. The notice itself was blunt: remaining inventory would be honored through existing prescriptions, but no new patients would be started and no guarantee existed past the current supply cycle, language her endocrinologist read aloud to her directly rather than paraphrase, since the distinction between "available today" and "available next quarter" is the entire decision in front of them.
The 2025 AGA gastroparesis guideline (Staller and colleagues) conditionally recommends two agents for use — metoclopramide and erythromycin — and issues a conditional recommendation against domperidone as first-line therapy, alongside prucalopride, aprepitant, nortriptyline, buspirone, and cannabidiol. The recommendations track what cleared the panel's evidence threshold rather than what carries FDA approval; erythromycin has no gastroparesis indication either. That leaves Renata in an unusual position: of the two agents the guideline actually endorses, one has just been withdrawn from her by an adverse effect and the other is the fallback now being weighed. The guideline itself records that the sole US supplier for the domperidone IND was exiting the business — so her access problem isn't a gap the guideline failed to anticipate, it is a fact the guideline documents and cannot solve.
Planning around a drug that may not be there in six months
Metoclopramide is off the table for her, full stop — an emerging extrapyramidal sign at week ten is exactly the finding the boxed warning exists to catch, and continuing or restarting it isn't a reasonable option regardless of what happens with domperidone.
Domperidone is the pharmacologically correct next step precisely because it doesn't meaningfully cross the blood-brain barrier — its whole appeal is central-nervous-system exposure metoclopramide has and domperidone doesn't. I'd rather get her onto it through the IND pathway while it still exists than wait and lose the option entirely.
I don't disagree on the mechanism — domperidone's peripheral selectivity is real and it is the better-matched drug for a patient who's already shown a central dopaminergic sign on metoclopramide.
But the supply notice isn't a hypothetical risk to hedge against later — the sole U.S. importer has already told prescribers it's exiting. Starting her on a drug with a known expiration date on its own access, without a real bridge plan, sets her up for an unplanned gap the next time her bakery's schedule doesn't have room for one.
That's a fair point about timing — I hadn't been thinking of the IND exit as something to plan the transition around rather than just watch happen. I'd still rather get her started now, while access is real, than default to erythromycin as the primary plan for someone I think domperidone genuinely fits better.
What I'd propose is starting domperidone now through the pathway that's still open, with erythromycin identified explicitly as the fallback and low-dose amitriptyline for symptom modulation kept in reserve — not waiting for the supply to actually run out before we have a next step ready.
Domperidone started at 10mg three times daily through the FDA IND pathway, with QT monitoring given the drug's own separate safety signal, and erythromycin named explicitly in her chart as the fallback plan rather than left undecided.
Not resolved: how her care should actually transition if the IND pathway closes mid-therapy rather than at a clean visit interval — both physicians agreed this needs a concrete answer before it becomes an emergency, not after.