Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 5mg/mL (50mg/10mL) single-dose ampule
Acquired Methemoglobinemia
If methemoglobin level remains >30% or if clinical symptoms persist, repeat dose up to 1 mg/kg 1 hr after the first dose
Ifosfamide-induced Encephalopathy (Off-Label)
Prevention: 50 mg IVq6-8hr
Treatment: 50 mg once or q4-8hr until symptoms resolve
Dosing Considerations
Methemoglobinemia indication is approved under accelerated approval
Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials
Dosing modifications
Renal impairment
- Mild renal impairment (eGFR 60 – 89 mL/min/1.73 m2): No dose adjustment recommended
- Moderate or severe renal impairment (eGFR 15-59 mL/min/1.73 m2): 1 mg/kg (one dose)
- If methemoglobin level remains >30% or if clinical symptoms persist 1 hr after dosing, consider initiating alternative interventions for methemoglobinemia
Hepatic impairment
- Methylene blue is extensively metabolized in the liver; monitor patients with any hepatic impairment for toxicities and potential drug interactions for an extended period of time following dosing
Dosage Forms & Strengths
injectable solution
- 5mg/mL (50mg/10mL) single-dose ampule
Acquired Methemoglobinemia
If methemoglobin level remains >30% or if clinical symptoms persist, repeat dose up to 1 mg/kg 1 hr after the first dose
Dosing Considerations
Methemoglobinemia indication is approved under accelerated approval
Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (5)
- cyproheptadine
methylene blue, cyproheptadine. Other (see comment). Contraindicated. Comment: MAO inhibitors may prolong and intensify the anticholinergic effects of antihistamines. Cyproheptadine may diminish the serotonergic effect of MAO inhibitors.
- desvenlafaxine
methylene blue and desvenlafaxine both increase serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first
- deutetrabenazine
methylene blue, deutetrabenazine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Deutetrabenazine should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI. If methylene blue must be used emergently, discontinue deutetrabenazine and monitor for adverse effects. Deutetrabenazine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- fluoxetine
methylene blue and fluoxetine both increase serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue fluoxetine immediately and monitor for CNS toxicity. Fluoxetine may be resumed 24 hours after last methylene blue dose or after 5 weeks of monitoring, whichever comes first.
- vortioxetine
methylene blue increases toxicity of vortioxetine by serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be urgently administered, discontinue vortioxetine immediately and monitor for serotonin syndrome. Monitor for serotonin syndrome for 3 weeks or 24 hr after last methylene blue dose, whichever comes first. Vortioxetine may be resumed 24 hr after last methylene blue dose.
Serious - Use Alternative (83)
- 5-HTP
methylene blue and 5-HTP both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
- alfentanil
methylene blue and alfentanil both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- almotriptan
almotriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- amitriptyline
methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- amoxapine
amoxapine and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- belladonna alkaloids
methylene blue and belladonna alkaloids both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- belladonna and opium
methylene blue and belladonna and opium both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- benzhydrocodone/acetaminophen
methylene blue increases toxicity of benzhydrocodone/acetaminophen by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- buprenorphine
methylene blue and buprenorphine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- bupropion
bupropion and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- buspirone
methylene blue and buspirone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- butalbital
methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- butorphanol
methylene blue and butorphanol both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- citalopram
methylene blue and citalopram both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- clomipramine
methylene blue and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- cocaine topical
methylene blue and cocaine topical both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. Cocaine inhibits presynaptic reuptake of serotonin. Monitor for CNS toxicity.
- codeine
methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- cyclobenzaprine
methylene blue and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first
- desipramine
methylene blue and desipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- dexfenfluramine
methylene blue and dexfenfluramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- dextroamphetamine
methylene blue and dextroamphetamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- dextromethorphan
methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- dihydroergotamine
methylene blue and dihydroergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- dihydroergotamine intranasal
methylene blue and dihydroergotamine intranasal both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- doxepin
methylene blue and doxepin both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- doxepin cream
methylene blue and doxepin cream both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- doxylamine
methylene blue and doxylamine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- duloxetine
methylene blue and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- eletriptan
eletriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- ergotamine
methylene blue and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- escitalopram
methylene blue and escitalopram both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- fentanyl
methylene blue and fentanyl both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- fluvoxamine
fluvoxamine increases toxicity of methylene blue by serotonin levels. Avoid or Use Alternate Drug.
- frovatriptan
frovatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- hydrocodone
methylene blue increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- hydromorphone
methylene blue and hydromorphone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- imipramine
methylene blue and imipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- isocarboxazid
methylene blue and isocarboxazid both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- isoniazid
methylene blue and isoniazid both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue and isoniazid may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue isoniazid immediately and monitor for CNS toxicity. Isoniazid may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- L-tryptophan
methylene blue and L-tryptophan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- levodopa
methylene blue and levodopa both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- levomilnacipran
methylene blue and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- levorphanol
methylene blue and levorphanol both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- linezolid
methylene blue and linezolid both increase serotonin levels. Avoid or Use Alternate Drug. Both drugs increase serotonin as a result of MAO-A inhibition. Avoid coadministration if possible. If coadministered, monitor for CNS toxicity.
- lsd
methylene blue and lsd both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity.
- maprotiline
methylene blue and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- meperidine
methylene blue and meperidine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- metformin
methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- methadone
methylene blue and methadone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- milnacipran
methylene blue and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- mirtazapine
methylene blue and mirtazapine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- morphine
methylene blue and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue morphine (if possible) and monitor for CNS toxicity. Morphine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- naratriptan
naratriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- nefazodone
methylene blue and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- nortriptyline
methylene blue and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- oxycodone
methylene blue and oxycodone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- paroxetine
methylene blue and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- pentazocine
methylene blue and pentazocine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue pentazocine (if possible) and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- phenelzine
methylene blue and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- procarbazine
methylene blue and procarbazine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- promethazine
methylene blue and promethazine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- protriptyline
methylene blue and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- rasagiline
methylene blue and rasagiline both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and rasagiline may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- remifentanil
methylene blue and remifentanil both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- rizatriptan
rizatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- safinamide
methylene blue, safinamide. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and safinamide may increase serotonin as a result of MAO-A inhibition. If IV methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- SAMe
methylene blue and SAMe both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- selegiline
selegiline and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and selegiline may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- selegiline transdermal
selegiline transdermal and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and selegiline may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- sertraline
methylene blue and sertraline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- St John's Wort
methylene blue and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- sufentanil SL
methylene blue increases toxicity of sufentanil SL by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- sumatriptan
sumatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- sumatriptan intranasal
sumatriptan intranasal and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- tedizolid
tedizolid, methylene blue. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase levels of serotonin; increased risk of serotonin syndrome.
- tramadol
methylene blue and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- tranylcypromine
methylene blue and tranylcypromine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- trazodone
methylene blue and trazodone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- trimipramine
methylene blue and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- valbenazine
methylene blue, valbenazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of valbenazine with MAOIs may increase monoamine neurotransmitter concentration in synapses, potentially increasing risk of serotonin syndrome or attenuating valbenazine effect.
- venlafaxine
methylene blue and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- vilazodone
methylene blue and vilazodone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- zolmitriptan
zolmitriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
Monitor Closely (8)
- artesunate
methylene blue will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- buprenorphine subdermal implant
methylene blue, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
- buprenorphine, long-acting injection
methylene blue, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
- lasmiditan
methylene blue increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.
- levodopa inhaled
levodopa inhaled increases effects of methylene blue by dopaminergic effects. Use Caution/Monitor. Coadministration of selective MAO-B inhibitors with levodopa may be associated with orthostatic hypotension.
- methoxsalen
methoxsalen, methylene blue. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.
- oliceridine
methylene blue, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
- tapentadol
methylene blue and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.
Minor (0)
Adverse Effects
>10%
Pain in extremity (84%)
Chromaturia (74%)
Dysgeusia (20%)
Feeling hot (17%)
Dizziness (16%)
Hyperhidrosis (13%)
Nausea (13%)
Skin discoloration (13%)
1-10%
Headache (10%)
Musculoskeletal pain (9%)
Paresthesia oral (9%)
Paresthesia (9%)
Infusion site pain (6%)
Feeling cold (6%)
Pallor (5%)
Contact dermatitis (5%)
Syncope (4%)
Pruritus (4%)
Anxiety (4%)
Decreased appetite (4%)
Chest discomfort (4%)
Back pain (2%)
Cold sweat (2%)
Dizziness postural (2%)
Muscle spasms (2%)
Presyncope (2%)
Arthralgia (2%)
Chills (2%)
Diarrhea (2%)
Discomfort (2%)
Dyspnea (2%)
Erythema (2%)
Hypoesthesia oral (2%)
Infusion site discomfort (2%)
Limb discomfort (2%)
Oral discomfort (2%)
Catheter site pain (2%)
Ecchymosis (2%)
Warnings
Black Box Warnings
May cause serious or fatal serotonergic syndrome when coadministered with serotonergic drugs
Avoid coadministration with SSRIs, SNRIs, and MAOIs
Contraindications
Severe hypersensitivity reactions to methylene blue or any other thiazine dye
Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia
Cautions
Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, bronchospasm) reported; monitor vital signs and ECG during treatment; if severe hypersensitivity occurs, discontinue drug and initiate supportive treatment (see Administration and Contraindications)
Methemoglobinemia may not resolve or may rebound after response to treatment due to aryl amines (eg, aniline, sulfa drugs [dapsone]); monitor response to therapy with through resolution of methemoglobinemia
Patients with G6PD deficiency may not reduce methylene blue to its active form in vivo and thereby be ineffective (see Contraindications)
The presence of methylene blue in the blood may result in an underestimation of the oxygen saturation reading by pulse oximetry
A fall in the Bispectral Index (BIS) has been reported following administration of methylene blue class products; if methylene blue is administered during surgery, alternative methods for assessing the depth of anesthesia should be employed
May cause confusion, dizziness, and disturbances in vision; patients should refrain from driving or engaging in hazardous occupations or activities
Methylene blue is a blue dye that passes freely into the urine and may interfere with the interpretation of any urine test which relies on a blue indicator (eg, dipstick test for leukocyte esterase)
Methylene blue is extensively metabolized in the liver; monitor patients with any hepatic impairment for toxicities and potential drug interactions for an extended period of time following treatment
Approximately 40% of methylene blue is excreted by the kidneys; patients with any renal impairment should be monitored for toxicities and potential drug interactions for an extended period of time following treatment
Hemolysis
- Hemolysis can occur during treatment of methemoglobinemia with methylene blue; laboratory testing may show Heinz bodies, elevated indirect bilirubin, and low haptoglobin, but the Coombs test is negative; anemia may occur; hemolytic anemia may not be apparent until ≥1 day after; anemia may require red blood cell transfusions
- Use lowest effective number of doses to treat methemoglobinemia; discontinue and consider alternative treatments of methemoglobinemia if severe hemolysis occurs
Serotonin syndrome
- Patients treated should be monitored for emergence of serotonin syndrome; if symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment; inform patients of the increased risk of serotonin syndrome and advise them not to take serotonergic drugs within 72 hours after last dose
- Symptoms associated with serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, and hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, and incoordination), seizures, and/or gastrointestinal symptoms(eg, nausea, vomiting, diarrhea); avoid concomitant use with serotonergic drugs
- Avoid coadministration with serotonergic psychiatric drugs (eg, SSRIs, SNRIs, TCAs, MAOIs) due to increased risk of serotonin syndrome, unless indicated for life-threatening conditions or when urgent treatment is required such as emergency treatment of methemoglobinemia, ifosfamide-induced encephalopathy, or cyanide poisoning; methylene blue may increase serotonin CNS levels by MAO-A inhibition
- If methylene blue must be administered to a patient currently taking a serotonergic drug, stop serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hours after the last dose of methylene blue, or after 2 weeks of monitoring (5 weeks if fluoxetine was taken), whichever comes first
- If possible, discontinue serotonergic psychiatric medication at least 2 weeks in advance of methylene blue treatment; fluoxetine should be stopped at least 5 weeks in advance due to longer half-life
- Also, see Black Box Warnings
Pregnancy & Lactation
Pregnancy
May cause fetal harm when administered to a pregnant woman
Intra-amniotic injection of pregnant women with a methylene blue class product during the second trimester was associated with neonatal intestinal atresia and fetal death
Lactation
There is no information regarding the presence of methylene blue in human milk, the effects on the breastfed infant, or the effects on milk production
Because of the potential for serious adverse reactions, including genotoxicity discontinue breastfeeding during and for up to 8 days after treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Methylene blue is a water soluble thiazine dye that promotes a nonenyzmatic redox conversion of metHb to hemoglobin
In situ, methylene blue is first converted to leucomethylene blue (LMB) via NADPH reductase; it is the LMB molecule which then reduces the ferric iron of metHb to the ferrous state of normal hemoglobin
It also combines with cyanide to form cyanmethemoglobin, which prevents the interference of cyanide with the cytochrome system
Absorption
Peak plasma concentration: 2,917 ng/mL
AUC: 13,977 ng·hr/mL
Distribution
Protein bound: 94%
Vd: 255 L
Metabolism
Metabolized by CYPs 1A2, 2C19 and 2D6 in vitro; however, the predominant in vitro pathway appears to be UGT-mediated conjugation by multiple UGT enzymes, including UGT1A4 and UGT1A9
Elimination
Half-life: 24 hr
Excretion: 40% unchanged in urine
Administration
IV Incompatibilities
0.9% NaCl (reduces methylene blue solubility)
Incompatible with caustic alkalis, iodides, dichromates, and oxidizing or reducing substances
IV Preparation
Solution is hypotonic and may be diluted before use in a solution of 50 mL D5W to avoid local pain, particularly in the pediatric population
Use the diluted solution immediately after preparation
Do not mix with 0.9% NaCl, because it has been demonstrated that chloride reduces the solubility of methylene blue
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
IV Administration
Ensure patent venous access prior to administration
For IV use only, do not administer SC or IM
Administer IV slowly over 5-30 minutes
If the methemoglobin level remains >30% or if clinical signs and symptoms persist, a repeat dose of 1 mg/kg may be given 1 hr after the first dose
If methemoglobinemia does not resolve after 2 doses, consider initiating alternative interventions for treatment of methemoglobinemia
Monitor vital signs, ECG, and methemoglobin levels during treatment and through resolution of methemoglobinemia
Storage
Store at 20-25°C (68-77°F)
Do not refrigerate or freeze
Keep ampule in original container to protect from light
Images
Formulary
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