Proveblue Drug Interactions

Methylthioninium chloride should be avoided in patients receiving medicinal products that enhance serotonergic transmission because of the potential for serious CNS reactions, including potentially fatal serotonin syndrome. These include SSRIs (selective serotonin reuptake inhibitors), bupropion, buspirone, clomipramine, mirtazapine, and venlafaxine. If the intravenous use of methylthioninium chloride cannot be avoided in patients treated with serotonergic medicinal products, the lowest possible dose should be chosen and the patient observed closely for central nervous system (CNS) effects for up to 4 hours after administration (see Precautions and Adverse Reactions).
Methylthioninium chloride is an in vitro inducer of CYP1A2. This interaction is not considered clinically relevant, since treatment with Methylthioninium chloride does not usually exceed one day.
In a drug interaction study, a single IV dose of 2 mg/kg Methylthioninium chloride did not have a clinically relevant effect on the pharmacokinetics of midazolam (CYP3A4), caffeine (CYP1A2), omeprazole (CYP2C19), warfarin (CYP2C9), and dextromethorphan (CYP2D6).
Methylthioninium chloride is a potent inhibitor of the transporters OCT2, MATE1 and MATE2-K. The clinical consequences of the inhibition are not known. The administration of Proveblue has the potential to transiently increase the exposure of drugs primarily cleared by renal transport involving the OCT2/MATE pathway, including cimetidine, metformin and acyclovir.
Methylthioninium chloride is a substrate of P-glycoprotein (P-gp). The clinical consequences are considered likely to be minimal due to the transient and single dose use that normally occurs in the emergency setting.