Methylene Blue

Methylene Blue is a prescription medication used to treat Acquired Methemoglobinemia.  

• Methylene Blue is available under the following different brand name: Provayblue.

Adult and pediatric dosage

Injectable solution

• 5mg/mL (50mg/10mL) single-dose ampule

Acquired Methemoglobinemia

Adult dosage

• 1 mg/kg IV over 5-30 minutes
• If methemoglobin level remains over 30% or if clinical symptoms persist, repeat dose up to 1 mg/kg 1 hour after the first dose 

Pediatric dosage

• 1 mg/kg IV over 5-30 minutes
• If methemoglobin level remains over 30% or if clinical symptoms persist, repeat dose up to 1 mg/kg 1 hour after the first dose 

Dosage Considerations – Should be Given as Follows: 

• See "Dosages."

Common side effects of Methylene Blue include:

• pain in the arms or legs, 
• blue or green urine, 
• altered sense of taste, 
• headache, 
• dizziness, 
• sweating, 
• skin discoloration, 
• nausea, and 
• feeling hot

Serious side effects of Methylene Blue include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• confusion, 
• weakness, 
• pale or yellow skin, 
• dark colored urine, 
• fever, 
• agitation, 
• hallucinations, 
• fast heart rate, 
• overactive reflexes, 
• nausea, 
• vomiting, 
• diarrhea, 
• loss of coordination, and 
• fainting 

Rare side effects of Methylene Blue include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Methylene Blue has severe interactions with the following drugs:
  • cyproheptadine
  • desvenlafaxine
  • deutetrabenazine
  • fluoxetine
  • vortioxetine
• Methylene Blue has serious interactions with at least 83 other drugs.
• Methylene Blue has moderate interactions with the following drugs:
  • artesunate
  • buprenorphine subdermal implant
  • buprenorphine, long-acting injection
  • lasmiditan
  • levodopa inhaled
  • methoxsalen
  • oliceridine
  • tapentadol
• Methylene Blue has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

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

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Methylene Blue?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Methylene Blue?”

Cautions

• Hypersensitivity reactions (e.g., 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 (e.g., 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)
• Hemolysis can occur during treatment of methemoglobinemia with methylene blue and anemia may occur; hemolytic anemia may not be apparent until 1 day after
• 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 which 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
• Serotonin syndrome
  • Avoid coadministration with serotonergic psychiatric drugs (e.g., 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 and Lactation

• 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.