BOXED WARNING Serotonin syndrome (serious or fatal) with concomitant serotonergic drugs (SSRIs, SNRIs, MAOIs) and opioids - avoid concomitant use.
FDA dosing
Population
Start
Target
Max
Acquired methemoglobinemia
Adults and pediatric patients
1 mg/kg IV over 5-30 min
1 mg/kg
may repeat 1 mg/kg once at 1 hour (2 doses total)
Renal Moderate or severe renal impairment (eGFR 15-59 mL/min/1.73m2): single 1 mg/kg dose; no adjustment for mild impairment (eGFR 60-89).
Hepatic Extensively hepatically metabolized; monitor patients with hepatic impairment longer for toxicity and drug interactions due to delayed clearance (no specific dose adjustment).
If methemoglobin remains >30% or symptoms persist, repeat 1 mg/kg at 1 hour; if unresolved after 2 doses, consider alternative interventions.
Instructions
IV only - do not administer subcutaneously; ensure patent venous access
May dilute in 50 mL of 5% Dextrose to reduce local pain (esp. pediatric); use immediately
Do not dilute with sodium chloride solutions (chloride reduces solubility)
Use methods other than pulse oximetry to assess oxygen saturation
Available strengths
inj 5 mg/mL
sol 1 g/100 mL
Contraindications
Glucose-6-phosphate dehydrogenase (G6PD) deficiency (risk of hemolytic anemia)
Cautions
Serotonin syndrome with serotonergic drugs and opioids
Hypersensitivity/anaphylaxis
Lack of effectiveness (aniline/dapsone-induced methemoglobinemia; G6PD deficiency) - consider alternatives if no response after 2 doses
Hemolytic anemia (onset may be delayed >=1 day; may require transfusion)
Interferes with pulse oximetry and bispectral index (BIS) monitoring
May impair ability to drive/operate machinery (confusion, dizziness, visual disturbance)
Interferes with laboratory tests
Adverse reactions
Headache
Hypokalemia
Diarrhea
Hypomagnesemia
Myoclonus
Nausea
Seizure-like phenomena
Pregnancy May cause fetal harm; intra-amniotic exposure associated with neonatal intestinal atresia and fetal death; animal developmental toxicity - use only if benefit justifies risk.
Lactation No data on presence in human milk; because of potential serious adverse reactions incl. genotoxicity, discontinue breastfeeding during and for up to 8 days after treatment.
Cost
Methylene blue (PROVAYBLUE)
Strength
#/mo
generic $/unit
CostPlus
5 mg/mL
inj
per unit
not offered
NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Methylene blue is administered under clinical supervision and dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.
Serotonin and MAOI
Provisional washout figures
SRI significance0 / 4
MAO-A inhibition3 / 4
Serotonin release0 / 4
Elevating mechanismMAO-A inhibitor
Evidence confidenceModerate
InterpretationSerotonergic danger is MAO-A inhibition, not reuptake blockade (Ramsay, Dunford & Gillman 2007). The previous sri=1 was an unreviewed stray and would have made this the only SERT+MAO-A molecule in the library.