Methylene Blue

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

The usual dose of oral methylene blue is 1 or 2 tablets after meals, 3 times per day.

Take the methylene blue tablet after a meal, with a full glass (8 ounces) of water.

Methylene blue injection is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

To be sure this medication is helping your condition, your blood may need to be tested often. This will help your doctor determine how long to treat you with methylene blue. Visit your doctor regularly.

Methylene blue will most likely cause your urine or stools to appear blue or green in color. This is a normal side effect of the medication and will not cause any harm.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using methylene blue.

Store methylene blue tablets at room temperature away from moisture, heat, and light.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Thiazine dye;9 accelerates conversion of methemoglobin to hemoglobin.113 115

Administration

Administer by slow IV injection over several minutes.1 2 Has been given by IV infusion†.9 113 115 118

Has been administered orally†,9 102 113 117 139 but oral preparations no longer commercially available in the US.a Oral solutions have been prepared extemporaneously by diluting 5–10 mL of the commercially available 10-mg/mL solution for IV use in 100–200 mL of water.9

Has been administered by local instillation or injection† for use as a diagnostic (visualizing) dye†.9 104 105 120 121 122 123 124

Has been administered topically† for use as a photosensitizer in PDT†.9 125 126 127 128 134 135 (See Administration Precautions under Cautions.)

Do not administer by sub-Q, intrathecal, or intraspinal injection.1 2 (See Administration Precautions under Cautions.)

IV Administration

Avoid extravasation and high local concentrations.1 2 (See Administration Precautions under Cautions.)

Inject slowly over several minutes (usually 3–10 minutes).1 2 9 113 115 116 117

Dosage

Pediatric Patients

1–2 mg/kg by slow IV injection.1 2 9 113 115 116 117

Symptomatic improvement usually occurs within 30 minutes.113 115 Repeat IV dose after 30–60 minutes if required.9 113 115 116 117

Adults

1–2 mg/kg by slow IV injection.1 2 9 113 115 116 117

Symptomatic improvement usually occurs within 30 minutes.113 115 Repeat IV dose after 30–60 minutes if required.9 113 115 116 117

50 mg by slow IV injection over ≥5 minutes;102 1–6 doses daily until symptoms resolve.102

Prescribing Limits

Pediatric Patients

Maximum dosage 2 mg/kg.1 2 Some experts recommend maximum total dose of 5–7 mg/kg during first few hours of treatment.9 115

Adults

Maximum dosage 2 mg/kg.1 2 Some experts recommend maximum total dose of 5–7 mg/kg during first few hours of treatment.9 115

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 2

Renal Impairment

Use with caution in patients with severe renal impairment.2 Reduced initial dosage may not be necessary in patients with renal impairment,115 but consider Clcr if given by continuous IV infusion†.115

• If you have an allergy to methylene blue or any other part of methylene blue.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have G6PD deficiency.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding. Do not breast-feed while you take methylene blue or within 8 days after your last dose.
• If this medicine is not being given into a vein. This medicine must not be given into the spine. Talk with the doctor.

This is not a list of all drugs or health problems that interact with methylene blue.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Dizziness or passing out.
• Feeling confused.
• Headache.
• Upset stomach or throwing up.
• Sweating a lot.
• A heartbeat that does not feel normal.
• Shortness of breath.
• Chest pain.
• Fever.
• Feeling very tired or weak.
• Pale skin.
• A burning, numbness, or tingling feeling that is not normal.

• If you need to store methylene blue at home, talk with your doctor, nurse, or pharmacist about how to store it.

Methylene blue, in low concentrations, hastens the conversion of methemoglobin to hemoglobin; has opposite effect at high concentrations by converting ferrous ion of reduced hemoglobin to ferric ion to form methemoglobin; in cyanide toxicity, it combines with cyanide to form cyanmethemoglobin preventing the interference of cyanide with the cytochrome system

In the treatment of vasoplegia syndrome, methylene blue may be able to restore vascular tone by a direct inhibitory effect on endothelial nitric oxide synthase (eNOS), and probably inducible NOS (iNOS), by oxidation of enzyme-bound ferrous iron. Methylene blue also blocks the formation of cyclic guanosine monophosphate (cGMP) by inhibiting the guanylate cyclase enzyme through binding to iron in the heme complex and subsequently reducing vasorelaxation (Lenglet 2011).

Absorption

Oral: 53% to 97% (Clifton 2003)

Distribution

255 L ± 58 L

Metabolism

Likely undergoes first pass metabolism or distribution; peripheral reduction to leukomethylene blue (Peter 2000)

Excretion

Generic: In bile, feces, and urine (~33% as leukomethylene blue) (Clifton 2003; Peter 2000)

ProvayBlue: Urine (~40% unchanged)

Methemoglobinemia (acquired): Neonates, Infants, Children, and Adolescents: IV: Refer to adult dosing.

Methemoglobinemia (drug induced): Children and Adolescents: IV: Refer to adult dosing.

Use of some products may be contraindicated by the manufacturer in women who are or may become pregnant. In general, medications used as antidotes should take into consideration the health and prognosis of the mother (Bailey 2003).

Use during amniocentesis has shown evidence of fetal abnormalities (atresia of the ileum and jejunum, ileal occlusions); has been used orally without similar adverse events; (Bailey 2003). Adverse events in the newborn following intra-amniotic injection near term also include hyperbilirubinemia, skin staining, and respiratory distress. In addition, hemolytic anemia, methemoglobinemia, and phototoxicity have been reported in neonates following in utero exposure (Burnakis 1995; Porat 1996; Vincer 1987). Based on studies in nonpregnant women, potential exposure to the fetus may be less when methylene blue is used for lymphatic mapping in breast cancer (Pruthi 2011). Monitor the newborn for adverse events if administered near term.