Safety Updates

Dear Healthcare Professional,
American Regent, Inc., would like to reinforce the appropriate preparation of ProvayBlue® (methylene blue) injection, 0.5%, USP with a solution of 50 mL 5% Dextrose in Water. There are reports of potential medication errors associated with the improper preparation of this product using saline (0.9% sodium chloride solution) which led to precipitation of the drug, since chloride reduces the solubility of methylene blue.

ProvayBlue® is an oxidation-reduction agent indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

All lots of Caffeine and Sodium Benzoate Injection, USP, 250 mg/mL, 2 mL Single Dose Vials,
manufactured and distributed by American Regent, Inc. in commercial distribution may exhibit
evidence of visible or sub-visible particles.

Internal procedures are in place to detect visible particles that may be present in Caffeine and Sodium
Benzoate Injection, USP, prior to release. Each lot is 100% inspected by automated inspection
machinery that is designed to detect visible particles. In addition to automated inspection, samples of
filled product are visually examined by Quality Assurance as part of normal lot release procedures. All
lots that have been released for distribution have been inspected in this manner, and have met all release
specifications for particulates. However, there is a potential for the transient appearance of particles
that represent trace amounts of the product’s active ingredient.

As a precautionary measure, a filter must be used for the withdrawal and administration of all
lots of Caffeine and Sodium Benzoate Injection, USP.