TheraRadar
Data updated: May 26, 2026

PROVAYBLUE (methylene blue)

Trial Activity: Stable 7 active trials
Other Approved 2016-04-08

PROVAYBLUE helps patients with acquired methemoglobinemia, a condition that affects both children and adults. It is used to restore the blood's ability to carry oxygen properly by acting as an oxidation-reduction agent. This medication is prescribed to convert abnormal hemoglobin back into its functional form.

Source: FDA Label • PROVEPHARM SAS

How PROVAYBLUE Works

This drug works by first converting into leucomethylene blue through a specific enzyme in the body. This active form then reduces the ferric iron in methemoglobin back to the ferrous state found in normal hemoglobin. This process allows for the non-enzymatic conversion of abnormal hemoglobin into a functional state.

Development Insights

University of Rochester conducting 3 trials (10%)
54 indications explored (Broad Platform)
septic shock (4 trials)
malignant neoplasm (3 trials)
oral pain (3 trials)
2
Indications
--
Phase 3 Trials
10
Years on Market

Details

Status
Prescription
First Approved
2016-04-08
Patent Cliff
2027

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Routes
INTRAVENOUS
Dosage Forms
SOLUTION

Companies

Active Ingredient: METHYLENE BLUE

PROVAYBLUE Approval History

2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
Original
New Indication
New Form
Label Update
26 FDA actions from 2016 to 2024 · 1 indication expansions
Dec 2024 SUPPL
Label · Labeling
Feb 2024 SUPPL
Label · Labeling
Jan 2024 SUPPL
Efficacy

What PROVAYBLUE Treats

1 indications

PROVAYBLUE is approved for 1 conditions since its original approval in 2016. These indications span multiple therapeutic areas including oncology, immunology, and more.

  • Methemoglobinemia
Source: FDA Label

PROVAYBLUE Boxed Warning

SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid concomitant use of PROVAYBLUE with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and opioids. [see Warnings and Precautions ( 5.1 ) and Drug Interactions ( 7.1 )]. WARNING: SEROTONIN SYNDROME WITH CONCOMI...

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METHYLENE BLUE
METHYLENE BLUE
1 shared
Hikma
Shared indications:
Methemoglobinemia
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Clinical Trial Registry

29 trials
Trial Sponsor ID Phase Status Title
NCT05092165 BLUE BLUE Ph 2 completed Methylene Blue for the Prevention of Hypotension During Hemodialysis
NCT02240498 RSRB00049677 Ph 1 completed Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities
NCT07494773 HSC19626 Ph 1, Ph 2 not yet recruiting Topical Methylene Blue-Photodynamic Therapy (MB-PDT) for Burn Wound Infection
NCT06900140 BLUSH LHICU123 Ph 3 completed Adjunctive Methylene Blue in Septic Shock
NCT06052956 STUDY00008702 Ph 2 not yet recruiting Efficacy of Methylene Blue Photodynamic Therapy for Treatment of Deep Tissue Abscesses
NCT06532240 2024ky202 Ph 3 completed Methylene Blue for the Treatment of Septic Shock
NCT07212842 2.462.520 Ph 2 completed Methylene Blue-Enhanced Ultrafiltration Improves Outcomes After Cardiopulmonary Bypass
NCT07179003 STUDY00010960 Ph 2 not yet recruiting A Phase 2 Study of Methylene Blue Photodynamic Therapy for Treatment of Breast Abscesses
NCT07169487 IIT2025072 Ph 1 recruiting Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study
NCT06887036 MB_HBV Methylene Blue in chronic HBV Ph 2 recruiting Methylene Blue Treatment of Chronic Hepatitis B Virus Infection
NCT04635605 MB treatment of COVID19 Ph 2 completed Methylene Blue Treatment of COVID-19
NCT01847612 CAMFIB PI2013_843_0003 2013-000408-40 Ph 3 completed Use of Indocyanine Green Cholangiography and Methylene Blue to Detect Postoperative Biliary Fistula After Hepatectomy
NCT02478281 results posted 1MBL12002 Ph 1 completed Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Following a 1 mg/kg Intravenous Dose in Healthy Adults
NCT06660680 MBI HFBH2021011 (No. 2023AH050848) Ph 3 enrolling by invitation The Effect of Methylene Blue Infiltrating Injection on Anal Pain After Milligan-Morgan Surgery: A Randomized Controlled Clinical Study
NCT02380573 MB2 results posted HSC20150410H Ph 2 completed Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease
NCT04054999 results posted 18-006247 Ph 4 completed Methylene Blue vs Cyanokit for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients
NCT06306001 IIRP-2023-1820/F1 Ph 2, Ph 3 not yet recruiting Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock
NCT04187053 results posted HSC-DB-19-0873 Ph 4 completed Clinical and Microbiologic Outcomes of aPDT in the Non-surgical Treatment of Implant Inflammation
NCT03469284 results posted 2016-1051 NCI-2018-00822, 2016-1051 Ph 2 completed MOM's PAIN (Methylene Blue for Oral Mucositis' PAIN)
NCT03395223 MEBIPAM results posted PVP-2016003 2017-000290-37 Ph 4 completed MEthylene Blue In Patients With Acquired Methemoglobinemia
NCT04446871 SHOCKEM-Blue HCG/CEI-0252/17 Ph 2, Ph 3 completed Methylene Blue in Early Septic Shock
NCT01386879 results posted 11D.48 Ph 4 terminated Evaluation of Above the Cuff Suctioning During General Anesthesia
NCT05004805 COMBAT COMBAT Ph 2 completed COVID-19 Methylene Blue Antiviral Treatment
NCT02851108 BlueACTn results posted UniHD008 Ph 2 completed Methylene Blue Against Falciparum Malaria in Burkina Faso
NCT03446599 D17173 Ph 2 withdrawn Hemodynamic Effects of Methylene Blue vs Hydroxocobalamin in Patients at Risk of Vasoplegia During Cardiac Surgery
NCT03120637 CRuMBS ILBS-Septic Shock-01 Ph 4 completed Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue
NCT03177070 10871 Ph 2 completed Fluorescent Imaging & Methylene Blue: Ureter Study
NCT02831023 UCSF CHR # 15-16839 Ph 2 completed Phase 2 Efficacy Study of Primaquine and Methylene Blue
NCT01276054 results posted 1B-09-12 NCI-2010-02323 Ph 2 terminated Sentinel and/or Axillary Lymph Node Biopsy With or Without Axillary Reverse Mapping in Reducing Incidence and Severity of Arm Lymphedema in Stage 0-2 Patients.
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Active Pipeline

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Ongoing clinical trials by development phase

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Key Completed Trials

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Completed studies with published results, ranked by significance

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Trial Timeline

Full development history with FDA approval milestones

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Understanding FDA Approval Types
Count Type What it means
- ORIG Original approval - drug first enters market
- SUPPL - Efficacy New indication (new disease/condition approved)
- SUPPL - Labeling Label text changes (warnings, dosing updates)
- SUPPL - Manufacturing Production changes (new facility)
- SUPPL - Chemistry Formulation changes (new dosage strength)

Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.

PROVAYBLUE FDA Label Details

Indications & Usage

FDA Label (PDF)

PROVAYBLUE is indicated for the treatment of Methemoglobinemia.

⚠️ BOXED WARNING

WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid concomitant use of PROVAYBLUE with selective serotonin reuptake inhibitors (SSRIs), serot...

PROVAYBLUE Patents & Exclusivity

Exclusivity: Jan 2027

Exclusivity

M-303 Until Jan 2027
M-303 Until Jan 2027
M-303 Until Jan 2027
M-303 Until Jan 2027
Source: FDA Orange Book

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Data Sources

Data sourced from official FDA and NIH databases. Click links to verify on original sources.

How We Calculate These Metrics

Trial Activity Stage

Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.

Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.

  • Growth: High proportion of early-phase trials (Phase 1/2), active development
  • Expansion: Significant Phase 3 activity, approaching or pursuing approvals
  • Mature: Substantial Phase 4 post-marketing studies
  • Stable: Mixed phase distribution, steady development
  • Declining: Low active trial ratio, reduced R&D investment