methylene blue (Rx)

Brand and Other Names:Provayblue
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

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

Acquired Methemoglobinemia

1 mg/kg IV over 5-30 minutes 

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

Dosage Forms & Strengths

injectable solution

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

Acquired Methemoglobinemia

1 mg/kg IV over 5-30 minutes 

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

Next:

Interactions

Interaction Checker

and methylene blue

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            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%)

            Previous
            Next:

            Warnings

            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)

            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 leucocyte 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 (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
            Previous
            Next:

            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.

            more...
            Previous
            Next:

            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

            Previous
            Next:

            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

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous