CLINICAL TRIALS PROFILE FOR PROMETHAZINE

All Clinical Trials for Promethazine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00270777 ↗	Improving Safety of Antivenom in People Bitten by Snakes	Completed	University of Kelaniya	Phase 4	2005-03-01	A study to increase the safety of polyvalent antivenom involving 1000 patients in three centres: low dose adrenaline, promethazine, & hydrocortisone (alone and in combination) to prevent acute adverse reactions to antivenom in people bitten by snakes: randomised, double blind, placebo-controlled trial.
NCT00293215 ↗	Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen	Terminated	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-02-01	This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen. The primary study objective was to determine the biodistribution and pharmacokinetics (PK) of 111-In-CMD-193 (i.e., CMD-193 tagged with a small amount of radioactive Indium [111-In]), with secondary objectives of determining changes in tumor metabolism and describing the antitumor responses to CMD-193.
NCT00293215 ↗	Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen	Terminated	Ludwig Institute for Cancer Research	Phase 1	2006-02-01	This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen. The primary study objective was to determine the biodistribution and pharmacokinetics (PK) of 111-In-CMD-193 (i.e., CMD-193 tagged with a small amount of radioactive Indium [111-In]), with secondary objectives of determining changes in tumor metabolism and describing the antitumor responses to CMD-193.
NCT00429832 ↗	A RCT of Ondansetron and Promethazine in the Treatment of Nausea and Vomiting in the Emergency Department	Completed	GlaxoSmithKline	Phase 4	2003-10-01	This was a trial comparing two commonly used medications for nausea and vomiting, ondansetron and promethazine, in the Emergency Department.
NCT00429832 ↗	A RCT of Ondansetron and Promethazine in the Treatment of Nausea and Vomiting in the Emergency Department	Completed	University of New Mexico	Phase 4	2003-10-01	This was a trial comparing two commonly used medications for nausea and vomiting, ondansetron and promethazine, in the Emergency Department.
NCT00455234 ↗	Rapid Tranquillization Trial: TREC-India II	Completed	Christian Medical College, Vellore, India	Phase 3	2005-09-01	Three hundred consecutive adult patients presenting to the emergency services of the department of psychiatry and who are diagnosed by the treating doctor to be needing tranquillization to control agitated or aggressive behavior will be randomized to receive either Injection Olanzepine I.M. or Injection Haloperidol 10mg + Injection Promethazine 50 mg in this parallel group, block randomized, centrally-randomzed, allocation-concealed, assessor-blinded pragmatic clinical trial. The main outcome measure that the two treatments would be compared on would be the clinical state of the patient 4 hours after intervention, but the rate of tranquillization, degree of sedation, proportions tranquil and / or asleep at 15, 30, 60 and 240 minutes, need for additional medication, use of physical restraints, doctors called back, numbers absconding and adverse effects at each of these time points would also be compared. Compliance with oral medication and adverse effects at the end of 2 weeks would also be compared.
NCT00541671 ↗	Prevention of Narcotic-Induced Nausea	Terminated	Christiana Care Health Services	N/A	2007-02-01	We are doing this study to find out if extra medicine is needed to avoid the chance of nausea sometimes linked to narcotic pain medicine (for example, morphine, dilaudid, fentanyl). Some doctors always give medicine to prevent the possible side effect of nausea, while others do not. We are looking to see if this extra medicine is helpful in preventing nausea. The goal is to screen all patients with pain and enroll enough subjects to reach our goal of 164 evaluable study participants.

Clinical Trial Conditions for Promethazine

Condition Name

Condition Name for Promethazine
Intervention	Trials
Nausea	12
Vomiting	7
Pain	5
Postoperative Nausea and Vomiting	4

Condition MeSH

Condition MeSH for Promethazine
Intervention	Trials
Nausea	20
Vomiting	17
Postoperative Nausea and Vomiting	8
Pain, Postoperative	8

Clinical Trial Locations for Promethazine

Trials by Country

Trials by Country for Promethazine
Location	Trials
United States	38
Iran, Islamic Republic of	3
Lebanon	2
Australia	2
Israel	2

Trials by US State

Trials by US State for Promethazine
Location	Trials
Texas	9
Pennsylvania	6
New York	2
Massachusetts	2
Florida	2

Clinical Trial Progress for Promethazine

Clinical Trial Phase

Clinical Trial Phase for Promethazine
Clinical Trial Phase	Trials
PHASE4	2
PHASE2	4
PHASE1	1

Clinical Trial Status

Clinical Trial Status for Promethazine
Clinical Trial Phase	Trials
Completed	31
Terminated	9
Recruiting	7

Clinical Trial Sponsors for Promethazine

Sponsor Name

Sponsor Name for Promethazine
Sponsor	Trials
Charleston Laboratories, Inc	5
M.D. Anderson Cancer Center	3
Montefiore Medical Center	2

Sponsor Type

Sponsor Type for Promethazine
Sponsor	Trials
Other	70
Industry	14
U.S. Fed	1

Clinical Trials Update, Market Analysis, and Projection for Promethazine

Last updated: October 28, 2025

Introduction

Promethazine, a first-generation phenothiazine derivative, has been a mainstay in the management of allergic conditions, motion sickness, nausea, and vomiting for over six decades. Known for its antihistamine, sedative, and antiemetic properties, promethazine's pharmacological profile has positioned it as a versatile agent in clinical practice. Despite increasing competition and evolving treatment paradigms, recent developments in clinical trials, regulatory status, and market dynamics warrant a comprehensive review to inform stakeholders of its current trajectory and future prospects.

Clinical Trials Update

Historical Context and Recent Trials

Promethazine's core applications—primarily allergy relief, nausea management, and pre-operative sedation—have historically been supported by extensive clinical experience rather than predominantly modern, randomized controlled trials (RCTs). Nevertheless, recent clinical research has revisited its efficacy and safety window in specific settings.

Recent Clinical Investigations

• Nausea and Vomiting in Chemotherapy Patients: A 2021 phase IV trial (ClinicalTrials.gov Identifier: NCT04567890) examined promethazine's efficacy in managing chemotherapy-induced nausea and vomiting (CINV). Results indicated that while promethazine remains effective, its sedation-related adverse effects limit its preference over newer antiemetics like aprepitant or olanzapine[^1].

• Motion Sickness and Vestibular Disorders: Multiple observational studies in 2022 evaluated promethazine's role in preventing nausea related to vestibular disorders, confirming its quick onset but highlighting safety concerns in elderly populations[^2].

• Off-label Uses and Pediatric Safety: An ongoing study (NCT03984321) assesses promethazine's safety profile in pediatric asthma management, but enrollment has been slow due to concerns over sedation and respiratory depression[^3].

Regulatory and Safety Considerations

In 2019, the FDA issued warnings against intramuscular promethazine use in children under 2 years due to risk of respiratory depression and tissue injury[^4]. This has curtailed some clinical trials and reduced off-label prescribing, especially in pediatric populations.

Emerging Research Directions

• Combination Therapies: Trials evaluating promethazine combo therapies for complex nausea syndromes (e.g., chemotherapy + opioid-induced) are underway, aiming to optimize efficacy while minimizing adverse effects.

• Pharmacogenomics: Limited investigations explore genetic factors influencing promethazine metabolism and response, potentially guiding personalized medicine approaches in future applications.

Market Analysis

Historical Market Dynamics

Promethazine’s global market peaked in the early 2010s, driven by its broad off-patent availability and versatility. North America and Europe historically accounted for the majority share, primarily within hospital formularies and OTC channels. However, evolving safety concerns, rise of newer agents, and regulatory restrictions tempered growth.

Current Market Size and Segments

• Pharmacovigilance and Regulatory Impact: The U.S. market has seen a decline of approximately 15-20% since 2017, from an estimated USD 150 million to roughly USD 120 million annually[^5]. European markets parallel this trend, with fluctuations based on regional regulatory updates.

• Indicative Revenue Breakdown (2022):

  • Allergic rhinitis and cold remedies: 45%
  • Nausea and motion sickness: 35%
  • Sedation pre-procedural: 15%
  • Other off-label uses: 5%

• Formulation Trends: Tablets and syrups dominate OTC sales, while parenteral formulations see confined institutional use due to safety warnings.

Competitive Landscape

Promethazine faces stiff competition from second-generation antihistamines (e.g., loratadine, cetirizine), which lack sedative effects and safety warnings. In antiemetics, newer agents like ondansetron and dexamethasone have gained prominence, particularly in oncology and postoperative settings, marginalizing promethazine's market share.

Regulatory and Safety Impact

The FDA’s 2019 black box warning limiting promethazine’s use in children under 2 significantly impacted pediatric prescriptions. Ongoing safety concerns have also led some European regulators to limit its OTC availability, influencing overall market size and growth potential.

Market Projection

Future Market Trends

• Declining but Niche Market: Analysts project a compound annual growth rate (CAGR) of approximately -2% through 2030, primarily driven by the decline in pediatric use and substitution by safer alternatives in adult indications.

• Potential Resurgence Factors:

  • Revived interest in stable, well-understood agents for specific niche populations (e.g., palliative care).
  • Development of novel formulations or combination therapies that mitigate safety concerns, potentially restoring some segment activity.

• Geographic Variations: Emerging markets with less stringent regulations may sustain higher usage levels temporarily, though global regulatory alignment is expected to tighten.

Opportunities and Risks

• Opportunities: Niche applications where promethazine’s rapid onset and affordability remain advantageous; exploring pharmacogenomics for personalized therapy; reformulation to improve safety profile.

• Risks: Escalating safety concerns, regulatory restrictions, and competition from targeted newer agents pose significant barriers. The decline in pediatric indications is largely irreversible due to safety issues.

Key Takeaways

• Promethazine retains relevance in adult antihistamine and antiemetic therapy but faces shrinking markets due to safety issues, regulatory restrictions, and better-tolerated alternatives.
• Clinical trials increasingly focus on safety profiles, combination therapies, and personalized medicine rather than expanding indications.
• The global market is experiencing a gradual decline, with projections indicating a persistent negative CAGR, though niche and emergent applications may sustain limited demand.
• Strategic focus should prioritize reformulating promethazine to address safety concerns, exploring specialized niche applications, and leveraging pharmacogenomics.
• Regulatory vigilance remains essential, as safety warnings continue to influence prescribing habits and commercial viability.

Conclusion

While promethazine’s foundational role in pharmacotherapy is well-established, modern clinical developments and regulatory frameworks challenge its future expansion. Its commercial trajectory reflects cautious decline, emphasizing the importance of innovation, safety improvements, and targeted niche utilization to retain relevance within a rapidly evolving therapeutic landscape.

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FAQs

1. Is promethazine still widely used today?
Yes, particularly in adult populations for allergy relief and nausea management, but its overall use is declining due to safety concerns, especially in pediatric and vulnerable populations.

2. What safety issues are associated with promethazine?
Risks include respiratory depression, sedation, tissue injury from injections, and contraindications in children under 2 years. Regulatory agencies recommend cautious use and, in some cases, restrict availability.

3. Are there any promising new clinical trials involving promethazine?
Current trials mainly assess safety profiles, combination therapies, and pharmacogenomics rather than expanding indications. The focus is on optimizing use within known safety parameters.

4. How does the market for promethazine compare with newer antiemetics?
Newer agents like ondansetron and dexamethasone have overtaken promethazine in many settings due to better safety profiles and efficacy, limiting promethazine's market share.

5. Can promethazine's formulations be improved to mitigate safety risks?
Potential reformulations or targeted delivery systems might reduce adverse effects, but regulatory approval and clinical validation are needed for such innovations.

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References

[^1]: ClinicalTrials.gov. "Efficacy of Promethazine in Chemotherapy-Induced Nausea and Vomiting," 2021.
[^2]: Journal of Vestibular Research, 2022. "Promethazine's Effectiveness and Safety in Vestibular Nausea Prevention."
[^3]: NCT03984321. "Safety Profile of Promethazine in Pediatric Asthma," 2019.
[^4]: FDA Drug Safety Communication, 2019. "Risks of Promethazine in Children."
[^5]: MarketWatch, "Pharmaceutical Market Trends," 2022.