Promethazine Shortage: What Providers and Prescribers Need to Know in 2026

Promethazine hydrochloride injection has been an active ASHP-listed shortage throughout late 2025 and into 2026, placing pressure on hospital formularies, surgical teams, and emergency departments that rely on it as a first-line antiemetic and sedative adjunct. This article provides prescribers, nurses, and pharmacy staff with a practical clinical framework for managing the shortage, selecting appropriate alternatives, and advising patients whose outpatient prescriptions may also be affected.

Current Shortage Status (2026 Update)

Per ASHP's Drug Shortage Database, the following promethazine injection presentations are affected:

• Promethazine HCl 25 mg/mL, 1 mL ampules: Back-ordered; estimated release date late January 2026
• Promethazine HCl 50 mg/mL, 1 mL ampules (X-Gen): Back-ordered; no estimated release date

Oral and rectal formulations (tablets, syrup, suppositories) are not in shortage and remain broadly available for outpatient use.

Pharmacology Review: Why Providers Choose Promethazine

Promethazine is a phenothiazine derivative with a multi-receptor profile that makes it clinically versatile:

• H1 antagonism: Antihistamine effects for allergy and sedation
• D2 antagonism: Antiemetic effects via mesolimbic dopamine receptor blockade
• Anticholinergic activity: Additional antiemetic contribution and sedation potentiation
• Alpha-adrenergic blockade: Contributes to sedation; also the mechanism behind hypotension risk

This multi-receptor activity means promethazine cannot always be replaced by a single-mechanism agent. Formulary substitution should be tailored to the clinical use case.

Formulary Substitution Recommendations by Use Case

Postoperative Nausea and Vomiting (PONV)

First-line alternative: Ondansetron 4 mg IV. Ondansetron is well-established for PONV with fewer extrapyramidal effects and lower sedation burden than promethazine. Consider adding dexamethasone 4-8 mg IV for high-risk PONV patients.

Second-line for refractory PONV: Metoclopramide 10 mg IV or prochlorperazine 10 mg IV.

Emergency Department Nausea and Vomiting

Randomized controlled trial data shows ondansetron 4 mg IV and promethazine 25 mg IV produce equivalent nausea reduction at 30 minutes (both approximately -34 to -36 mm on a 100 mm VAS). Ondansetron was associated with significantly less sedation (5 mm vs 19 mm) and fewer extrapyramidal reactions. For undifferentiated nausea in adult ED patients, ondansetron is a direct substitution.

Surgical Sedation Adjunct

Promethazine's sedative properties are used as a narcotic adjunct to reduce required opioid doses in perioperative settings. When promethazine injection is unavailable, consider: diphenhydramine 25-50 mg IV (H1 sedation without D2 effects), or lorazepam 0.5-2 mg IV for adjunctive anxiolysis (with appropriate monitoring).

Allergy Reactions (Adjunct to Epinephrine)

Note: Promethazine reverses the vasopressor effect of epinephrine and should NOT be used to treat promethazine-induced hypotension, nor as a first-line agent in anaphylaxis. Diphenhydramine 25-50 mg IV is a more appropriate antihistamine adjunct in anaphylaxis protocols.

Safety Considerations for Promethazine Substitutes

When selecting a substitution, be aware of the following safety considerations:

• Metoclopramide and prochlorperazine: Higher rate of acute dystonia and akathisia, especially in younger patients. Consider prophylactic diphenhydramine 25 mg in high-risk patients.
• Ondansetron: QT prolongation risk, particularly at higher doses. Avoid in patients with congenital long QT syndrome or on other QT-prolonging agents.
• Haloperidol and droperidol: Effective antiemetics but require QTc monitoring; higher extrapyramidal risk than promethazine.

Advising Outpatients About the Shortage

When patients ask about the shortage, providers should clarify:

• Oral tablets and suppositories are not in shortage — the injectable shortage is separate
• If a patient can't locate their promethazine tablet prescription, it may be a localized pharmacy issue rather than a true shortage
• Direct patients to try multiple pharmacies, or refer them to medfinder.com, which calls pharmacies on their behalf to find which ones can fill their prescription

Important Safety Reminder: Promethazine IV Route

Even when injectable promethazine supply is restored, the IV route of administration should be approached with extreme caution. Promethazine injection carries a boxed warning regarding severe tissue injury from extravasation or inadvertent intra-arterial injection, which can result in gangrene and tissue necrosis. IM administration is the preferred parenteral route when promethazine injection is clinically required.

How medfinder Helps Your Patients

If your patients are struggling to locate outpatient promethazine, medfinder.com/providers offers resources to help your practice support patients in finding medications. medfinder calls pharmacies near the patient to check which can fill the prescription, and delivers results by text — reducing callbacks to your office and improving patient outcomes.

For a more detailed provider workflow guide, see: How to Help Your Patients Find Promethazine in Stock: A Provider's Guide.