PROVAYBLUE

The mean (CV%) Cmax and AUC of methylene blue 2,917 ng/mL (39%) and 13977 ng.hr/mL (21%) following a 2 mg/kg dose administered as a 5-minute intravenous infusion.

DistributionThe mean± standard deviation steady state volume of distribution of a 2 mg/kg dose of PROVAYBLUE was 255 L ± 58. The mean plasma protein binding of methylene blue is approximately 94% in vitro. Methylene blue exhibits concentration-dependent partitioning into blood cells in vitro. The blood-to-plasma ratio was 5.1±2.8 at 5...

14.1 Treatment of Acquired Methemoglobinemia The efficacy of PROVAYBLUE in the treatment of patients with methemoglobinemia was evaluated in 31 adult patients with acquired methemoglobinemia across two studies: NCT03395223 , a prospective, interventional, open-label, single-arm study, and NCT03542760 , a prospective, multicenter, observational registry. Of the 31 subjects enrolled 90% were white, 10% were black, 58% were female, and 42% were male. Hispanic or Latino was 9.7%; non-Hispanic or Latino was 67.7%, and ethnicity data were missing for 22.6%. The mean age was 45.6 years, and the ages ...

The following adverse reactions are discussed in greater detail in other sections of the labeling: Serotonin Syndrome with Concomitant Use of Serotonergic Drugs [see Warnings and Precautions ( 5.1 )] Anaphylaxis [see Warnings and Precautions ( 5.2 )] Lack of Effectiveness [see Warnings and Precautions ( 5.3 )] Hemolytic Anemia [see Warnings and Precautions ( 5.4 )] Interference with In-Vivo Monitoring Devices [see Warnings and Precautions ( 5.5 )] Effects on Ability to Drive and Operate Machiner...

PROVAYBLUE is contraindicated in the following conditions: Severe hypersensitivity reactions to methylene blue or any other thiazine dye [see Warnings and Precautions ( 5.2 )] . Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia [see Warnings and Precautions ( 5.3 , 5.4 )]. PROVAYBLUE is contraindicated in the following conditions ( 4 ): Severe hy...

Hypersensitivity: If severe or life threatening allergic reaction occurs, discontinue PROVAYBLUE, treat the allergic reaction, and monitor until signs and symptoms resolve ( 5.2 ) Lack of Effectiveness: Consider alternative treatments if there is no resolution of methemoglobinemia after 2 doses ( 2.1 , 5.3 ) Hemolytic Anemia: Discontinue PROVAYBLUE and transfuse ( 5.4 ) Interference with In-Vivo Monitoring Devices: Use methods other than pulse oximetry to assess oxygen saturation ( 5.5 ) Effects...

7 DRUG INTERACTIONS Clinically significant drug interactions with PROVAYBLUE are described below: The concomitant use of PROVAYBLUE with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Although the mechanism is not clearly understood, literature reports suggest PROVAYBLUE is a potent reversible inhibitor of monoamine oxidase. Avoid concomitant u...