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Methylene Blue

Class: Antidotes
VA Class: AD200
Molecular Formula: C16H18CIN3S.3H2O
CAS Number: 7220-79-3

Introduction

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

Uses for Methylene Blue

Methemoglobinemia

Treatment of drug-induced methemoglobinemia.1 2

Used for methemoglobinemia associated with certain drugs (e.g., dapsone, benzocaine, lidocaine),117 118 occupational or other exposures to toxic chemicals (e.g., hydrazine, amine-substituted benzenes, nitro-substituted benzenes, nitrates, nitrites),111 113 115 or substance abuse (e.g., inhalation or ingestion of volatile nitrites).110 111 112 115

Does not reverse methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency;9 113 115 117 may induce or exacerbate hemolysis in these patients.2 113 115 (See Hematologic Effects under Cautions.)

Has been used for treatment of cyanosis in patients with congenital methemoglobinemia related to cytochrome b5 reductase deficiency;115 117 129 130 131 ineffective in patients with hemoglobin M (abnormal hemoglobin molecules).115 117 131

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Not effective for treatment of sulfhemoglobinemia.115 131

Ifosfamide-induced Encephalopathy

Management of ifosfamide-induced encephalopathy;102 may be beneficial in some patients, but additional study needed.102

Has been ineffective when used prophylactically in an attempt to prevent ifosfamide-associated encephalopathy.102 103

Use as a Dye

Has been used as a bacteriologic stain, as an indicator dye, and for surgical and medical marking.a

Has been used as diagnostic (visualizing) dye in a variety of procedures, including sentinel lymph node biopsy in cancer patients (e.g., breast cancer patients),9 120 123 endoscopic evaluation of lesions in patients with GERD or Barrett's esophagus,121 urologic evaluation in patients with ureteral or renal pelvis injury,122 and thoroscopic procedures in patients with pulmonary nodules.124

Photodynamic Therapy

Has been used as a photosensitizer for photodynamic therapy (PDT) for topical treatment of dermatologic or mucocutaneous infections (e.g., herpes labialis, eczema herpeticum, oral candidiasis, cutaneous leishmaniasis, chromoblastomycosis)26 127 128 134 135 or chronic dermatologic or mucocutaneous conditions (e.g., plaque psoriasis, oral lichen planus).125 126

Cyanide and Carbon Monoxide Poisoning

Was used in the past as an antidote for cyanide poisoning;113 no longer recommended for this use.9 Cyanide poisoning usually treated with antidote regimen consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate or with hydroxocobalamin.115 119

When sodium nitrite is used for cyanide poisoning, do not use methylene blue in an attempt to treat excessive methemoglobinemia induced by the antidote because reduced cyanide binding and increased toxicity occurs.9

Not effective for treatment of carbon monoxide poisoning.a

Cystitis and Urethritis

Was used in the past as a mild urinary antiseptic and stimulant to mucous surfaces in the treatment of cystitis and urethritis; no longer recommended for this use.a

Urolithiasis

Has been used alone and in combination with ascorbic acid for management of chronic urolithiasis.a May inhibit formation of calcium oxalate and calcium phosphate crystals, but not currently recommended for this use and is ineffective in dissolving previously formed stones.a

Methylene Blue Dosage and Administration

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.)

Rate of Administration

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

Dosage

Pediatric Patients

Drug-induced Methemoglobinemia
IV

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

Drug-induced Methemoglobinemia
IV

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

Ifosfamide-induced Encephalopathy
IV

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

Prescribing Limits

Pediatric Patients

Drug-induced Methemoglobinemia
IV

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

Drug-induced Methemoglobinemia
IV

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

Cautions for Methylene Blue

Contraindications

  • Known hypersensitivity to methylene blue.2

  • Women who are or may become pregnant.2 (See Fetal/Neonatal Morbidity under Warnings/Precautions.)

  • Sub-Q, intrathecal, or intraspinal injection.1 2 (See Administration Precautions under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

Potentially teratogenic;2 may cause fetal harm if used during pregnancy.2 9 141 143 144 145 146

Use in amniocentesis has been associated with atresia of the ileum and jejunum, ileal occlusion, and other adverse effects in neonates.2 9 (See Pediatric Use under Cautions.)

Contraindicated in women who are or may become pregnant; if used during pregnancy or if patient becomes pregnant, apprise patient of potential fetal hazard.2

Serotonin Syndrome

Serotonin syndrome reported in patients receiving methylene blue concomitantly with serotonergic drugs.2 100 101 Signs and symptoms of serotonin syndrome include mental changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering, shaking, diarrhea, loss of coordination, and/or fever.100

Most cases of serotonin syndrome occurred when methylene blue was used as a diagnostic (visualizing) dye (1–8 mg/kg IV) during parathyroid surgery in patients receiving a serotonergic drug; unclear whether there is a risk when methylene blue administered by other routes or in lower IV doses.101 Most cases occurred in patients receiving an SSRI (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), SNRI (e.g., desvenlafaxine, duloxetine, venlafaxine), or clomipramine.2 100 101 Not reported to date with concomitant use of vilazodone, but risk is considered comparable to that with SSRIs.101

FDA has not concluded whether concomitant use of methylene blue and other drugs with lesser degrees of serotonergic activity, including tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine), MAO inhibitors (isocarboxazid, phenelzine, transdermal selegiline, tranylcypromine), amoxapine, bupropion, buspirone, maprotiline, mirtazapine, nefazodone, or trazodone, is associated with a risk of serotonin syndrome comparable to that reported when methylene blue is used concomitantly with SSRIs or SNRIs.101

Methylene blue generally should not be used in patients receiving serotonergic drugs.2 100 FDA states that certain emergency situations (e.g., methemoglobinemia, ifosfamide-induced encephalopathy) may necessitate immediate methylene blue treatment in a patient receiving a serotonergic drug.100 In such situations, consider availability of alternative interventions and weigh benefits of methylene blue against risk of serotonin syndrome.100 If methylene blue is initiated, immediately discontinue the serotonergic drug.100 (See Serotonergic Drugs under Interactions.)

Hematologic Effects

Hemolysis and hemolytic anemia may occur,2 9 113 especially in young infants9 115 142 and patients with G-6-PD deficiency.2 113 115

Because of risk of paradoxical methemoglobinemia and hemolysis,2 avoid use in patients with known or suspected G-6-PD deficiency.2 106 117

High IV dosage or high local concentrations may cause formation of methemoglobin and cyanosis.1 2 9 113 115 To prevent local high concentrations and production of additional methemoglobin, give IV injections slowly and do not exceed recommended dosage.1 2 (See Prescribing Limits under Dosage and Administration.)

Long-term administration may result in marked anemia due to accelerated destruction of erythrocytes; frequently monitor hemoglobin concentrations.a

Administration Precautions

Imparts blue-green color to saliva, urine, feces, and skin;9 115 bluish skin discoloration from excessive dosage can be mistaken for methemoglobinemia.115

IV administration: Adverse local effects, including pain,113 burning sensation,9 rash,9 necrosis,9 abscess,9 ulceration,9 and thrombophlebitis9 reported; extravasation has caused tissue necrosis.113

Oral: Adverse GI effects and dysuria reported.9

Topical application: Skin may become stained; skin stains may be removed by hypochlorite solution.9

Sub-Q or intradermal injection: Adverse skin and tissue reactions (e.g., erythematous macular lesions, superficial ulcers, abscess formation, skin and fat necrosis) at injection site reported.107 108 (See Contraindications under Cautions.)

Intrathecal injection: Neural damage reported.9 (See Contraindications under Cautions.)

Sensitivity Reactions

Hypersensitivity, manifested as wheal and flare reactions at injection site, reported.114

Severe hypersensitivity reactions (e.g., anaphylaxis, generalized urticaria, hypotension, tachycardia, bronchospasm) reported following local instillation or injection.104 105 114

Epinephrine and other appropriate agents and equipment should be available for immediate use in case anaphylactic reaction occurs.105

Specific Populations

Pregnancy

Category X.2 (See Fetal/Neonatal Morbidity under Cautions.)

Use during pregnancy has resulted in hemolytic anemia, hyperbilirubinemia, methemoglobinemia, respiratory distress, skin staining, and phototoxicity in neonates.9 141 143 144 145 146

Pediatric Use

Hemolysis, hemolytic anemia, hyperbilirubinemia, and phototoxicity reported in neonates and young infants;142 fatalities reported.142

Renal Impairment

Use with caution in patients with severe renal impairment.2 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Large IV doses: Nausea,1 2 vomiting,9 abdominal pain,1 2 precordial pain,1 2 dizziness,1 2 headache,1 2 profuse sweating,1 2 dyspnea,9 hypertension,9 mental confusion.1 2

Interactions for Methylene Blue

No formal drug interaction studies conducted.1 2

Specific Drugs

Drug

Interaction

Comments

Antimalarial agents

Artemisinin, artemether, or artesunate: In vitro evidence of synergistic antimalarial effects against Plasmodium falciparum138

Mefloquine or quinine: In vitro evidence of additive antimalarial effects against P. falciparum138

Chloroquine or pyrimethamine: In vitro evidence of antagonistic antimalarial effects against P. falciparum138

Clinical importance unclear138

MAO inhibitors (isocarboxazid, phenelzine, transdermal selegiline, tranylcypromine)

Methylene blue is a potent MAO inhibitor;2 109 possible increased risk of serotonin syndrome2 100 101

Do not use methylene blue in patients who are receiving (or have received within the last 2 weeks) an MAO inhibitor2 100

Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, amoxapine, bupropion, buspirone, maprotiline, mirtazapine, nefazodone, trazodone, vilazodone)

Increased risk of serotonin syndrome, particularly with SSRIs and SNRIs;2 100 101 unclear whether risk associated with other serotonergic drugs is comparable to that reported with SSRIs and SNRIs101

Do not use concurrently;2 100 in certain emergency situations that necessitate immediate use of methylene blue (e.g., methemoglobinemia, ifosfamide-induced encephalopathy) in patient receiving a serotonergic drug, consider availability of alternative interventions and weigh benefits of methylene blue against risk of serotonin syndrome100

If emergency use of methylene blue is considered necessary, immediately discontinue the serotonergic drug; monitor closely for symptoms of CNS toxicity (e.g., mental changes, muscle twitching, excessive sweating, shivering/shaking, diarrhea, loss of coordination, fever) for 2 weeks (5 weeks if patient was receiving fluoxetine) or until 24 hours after last methylene blue dose, whichever comes first100

If nonemergency use of methylene blue is planned, withhold the serotonergic drug for at least 2 weeks (5 weeks if patient was receiving fluoxetine) prior to administering methylene blue;100 serotonergic drug may be resumed 24 hours after last methylene blue dose100

Do not initiate serotonergic drug in patient receiving methylene blue; when necessary, initiate 24 hours after last methylene blue dose100

Methylene Blue Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations occur approximately 1–2 hours after an oral dose.9

Oral absorption may be too slow and inconsistent for treatment of severe methemoglobinemia; IV administration necessary.113

Elimination

Metabolism

Following distribution into tissues, rapidly reduced to leukomethylene blue (leucomethylthioninium chloride).9

Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals.9

Elimination Route

Excreted in urine and bile.a About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue.a

On exposure to air, urine turns green or blue due to presence of oxidation product methylene azure (methylene blue sulfone).a

Some unchanged drug also excreted in urine.a

Half-life

IV administration: Estimated half-life is 5–6.5 hours.9 132

Stability

Storage

Parenteral

Solution for IV Use

20–25°C;1 2 may be exposed to 15–30°C.2

Actions

  • Low concentrations accelerate rate of conversion of methemoglobin to hemoglobin.1 2

  • High concentrations convert ferrous iron of reduced hemoglobin to ferric iron, resulting in methemoglobin formation.1 2

  • Acts as a photosensitizer when used in conjunction with light (photodynamic therapy);126 exact mechanism unclear.126 When activated by specific wavelengths of light, may act as a strong oxidizer to destroy targeted cells through cellular damage, altered membrane permeability, or protein inactivation.126 133 In vitro, exposure of Candida albicans to methylene blue and laser light resulted in increased membrane permeability and decreased yeast growth.133 Appears to bind irreversibly to viral nucleic acid and cause disruption of the virus molecule upon exposure to light.a

  • Has in vitro activity against Plasmodium falciparum, including strains with reduced susceptibility to chloroquine, quinine, monodesethylamodiaquine (active metabolite of amodiaquine; not commercially available in US), and mefloquine;136 137 138 140 clinical importance unclear.136 137 138 140 (See Specific Drugs under Interactions.)

  • Possesses weak antiseptic properties.a

  • Directly inhibits calcium binding by oxalate and by organic stone matrix.a Acts as a crystal poison at the interface, reducing tendency of calcium oxalate particles to aggregate.a In addition, reverses intracellular acidosis (such as that in renal tubule acidosis), apparently by competing with diphosphopyridine nucleotide as a hydrogen receptor.a

Advice to Patients

  • Advise patients of the potential risk of serotonin syndrome, particularly if methylene blue is used concomitantly with SSRIs, SNRIs, MAO inhibitors, tricyclic antidepressants, or other serotonergic drugs.100 Importance of immediately contacting clinician if signs or symptoms of serotonin syndrome develop (e.g., confusion, hyperactivity, memory problems, muscle twitching, excessive sweating, shivering, shaking, diarrhea, loss of coordination, fever).100 Importance of not discontinuing serotonergic drugs without first consulting clinician.100

  • Advise patients that saliva, urine, feces, and skin may have a blue-green discoloration.9 115 If administered by topical application, advise patients that skin may become stained; skin stains may be removed by hypochlorite solution.9

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 (See Fetal/Neonatal Morbidity under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

  • Importance of informing patients of other important precautionary information.1 2 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Methylene Blue

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

10 mg/mL*

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 20, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Akorn, Inc. Methylene blue injection, USP 1% prescribing information. Lake Forest, IL; 2011 Jun.

2. American Regent, Inc. Methylene blue injection, USP 1% prescribing information. Shirley, NY; 2011 Mar.

9. Methylthioninium chloride. In: Martindale: The complete drug reference. London: Pharmaceutical Press. From MedicinesComplete website. Accessed 2012 Feb 9.

26. Chang TW, Weinstein L. Eczema herpeticum. Treatment with methylene blue and light. Arch Dermatol. 1975; 111:1174-5. [PubMed 170870]

100. Food and Drug Administration. Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. 2011 Jul 26. From FDA website.

101. Food and Drug Administration. Drug Safety Communication: Updated information about the drug interaction between methylene blue (methylthioninium chloride) and serotonergic psychiatric medications. 2011 Oct 20. From FDA website.

102. Patel PN. Methylene blue for management of Ifosfamide-induced encephalopathy. Ann Pharmacother. 2006; 40:299-303. [PubMed 16391008]

103. Richards A, Marshall H, McQuary A. Evaluation of methylene blue, thiamine, and/or albumin in the prevention of ifosfamide-related neurotoxicity. J Oncol Pharm Pract. 2011; 17:372-80. [PubMed 20861178]

104. Dewachter P, Mouton-Faivre C, Tréchot P et al. Severe anaphylactic shock with methylene blue instillation. Anesth Analg. 2005; 101:149-50, table of contents. [PubMed 15976222]

105. Jangjoo A, Forghani MN, Mehrabibahar M et al. Anaphylaxis reaction of a breast cancer patient to methylene blue during breast surgery with sentinel node mapping. Acta Oncol. 2010; 49:877-8. [PubMed 20429734]

106. Youngster I, Arcavi L, Schechmaster R et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Saf. 2010; 33:713-26. [PubMed 20701405]

107. Stradling B, Aranha G, Gabram S. Adverse skin lesions after methylene blue injections for sentinel lymph node localization. Am J Surg. 2002; 184:350-2. [PubMed 12383900]

108. Salhab M, Al Sarakbi W, Mokbel K. Skin and fat necrosis of the breast following methylene blue dye injection for sentinel node biopsy in a patient with breast cancer. Int Semin Surg Oncol. 2005; 2:26. [PubMed 16313674]

109. Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007; 152:946-51. [PubMed 17721552]

110. Hunter L, Gordge L, Dargan PI et al. Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. Br J Clin Pharmacol. 2011; 72:18-26. [PubMed 21352269]

111. Centers for Disease Control and Prevention (CDC). Severe Methemoglobinemia and Hemolytic Anemia from Aniline Purchased as 2C-E (4-ethyl-2,5-dimethoxyphenethylamine), a Recreational Drug, on the Internet - Oregon, 2011. MMWR Morb Mortal Wkly Rep. 2012; 61:85-8. [PubMed 22318470]

112. Stambach T, Haire K, Soni N et al. Saturday night blue--a case of near fatal poisoning from the abuse of amyl nitrite. J Accid Emerg Med. 1997; 14:339-40. [PubMed 9315944]

113. Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003; 22:13-27. [PubMed 14579544]

114. Zakaria S, Hoskin TL, Degnim AC. Safety and technical success of methylene blue dye for lymphatic mapping in breast cancer. Am J Surg. 2008; 196:228-33. [PubMed 18367146]

115. Shannon MW, Borron SW, Burns MJ. Haddad and Winchester's clinical management of poisoning and drug overdose. 4th ed. Philadelphia, PA: Saunders, Elsevier; 2007. From MedicinesComplete website. Accessed 2012 Feb 9.

116. The Harriet Lane handbook. 19th ed. Philadelphia, PA: Mosby, Elsevier; 2012. From MedicinesComplete website. Accessed 2012 Feb 9.

117. Hoffman R, Benza EJ, Shattil SJ et al. Hematology: basic principles and practice. 5th ed. London: Churchill Livingstone, Elsevier; 2008. From MedicinesComplete website. Accessed 2012 Feb 9.

118. Barclay JA, Ziemba SE, Ibrahim RB. Dapsone-induced methemoglobinemia: a primer for clinicians. Ann Pharmacother. 2011; 45:1103-15. [PubMed 21852596]

119. Hamel J. A review of acute cyanide poisoning with a treatment update. Crit Care Nurse. 2011; 31:72-81; quiz 82. [PubMed 21285466]

120. Mathelin C, Croce S, Brasse D et al. Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer. Anticancer Res. 2009; 29:4119-25. [PubMed 19846959]

121. Freitas MC, Moretzsohn LD, Coelho LG. Prevalence of Barrett's esophagus in individuals without typical symptoms of gastroesophageal reflux disease. Arq Gastroenterol. 2008 Jan-Mar; 45:46-9.

122. Wein AJ, Kavoussi LR, Novick AC et al. Campbell-Walsh urology. 10th ed. Philadelphia, PA: Saunders, Elsevier; 2011. From MedicinesComplete website. Accessed 2012 Feb 9.

123. Varghese P, Abdel-Rahman AT, Akberali S et al. Methylene blue dye--a safe and effective alternative for sentinel lymph node localization. Breast J. 2008 Jan-Feb; 14:61-7.

124. Chen W, Chen L, Yang S et al. A novel technique for localization of small pulmonary nodules. Chest. 2007; 131:1526-31. [PubMed 17494801]

125. Salah M, Samy N, Fadel M. Methylene blue mediated photodynamic therapy for resistant plaque psoriasis. J Drugs Dermatol. 2009; 8:42-9. [PubMed 19180895]

126. Aghahosseini F, Arbabi-Kalati F, Fashtami LA et al. Treatment of oral lichen planus with photodynamic therapy mediated methylene blue: a case report. Med Oral Patol Oral Cir Bucal. 2006; 11:E126-9. [PubMed 16505788]

127. Biel MA. Photodynamic therapy of bacterial and fungal biofilm infections. Methods Mol Biol. 2010; 635:175-94. [PubMed 20552348]

128. Song D, Lindoso JA, Oyafuso LK et al. Photodynamic therapy using methylene blue to treat cutaneous leishmaniasis. Photomed Laser Surg. 2011; 29:711-5. [PubMed 21671755]

129. Da-Silva SS, Sajan IS, Underwood JP. Congenital methemoglobinemia: a rare cause of cyanosis in the newborn--a case report. Pediatrics. 2003; 112:e158-61. [PubMed 12897322]

130. Eder HA, Finch C, McKee RW. Congenital methemoglobinemia; a clinical and biochemical study of a case. J Clin Invest. 1949; 28:265-72. [PubMed 16695674]

131. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999; 34:646-56. [PubMed 10533013]

132. Peter C, Hongwan D, Küpfer A et al. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000; 56:247-50. [PubMed 10952480]

133. Giroldo LM, Felipe MP, de Oliveira MA et al. Photodynamic antimicrobial chemotherapy (PACT) with methylene blue increases membrane permeability in Candida albicans. Lasers Med Sci. 2009; 24:109-12. [PubMed 18157564]

134. Lyon JP, Pedroso e Silva Azevedo Cde M, Moreira LM et al. Photodynamic antifungal therapy against chromoblastomycosis. Mycopathologia. 2011; 172:293-7. [PubMed 21643843]

135. Marotti J, Sperandio FF, Fregnani ER et al. High-intensity laser and photodynamic therapy as a treatment for recurrent herpes labialis. Photomed Laser Surg. 2010; 28:439-44. [PubMed 19821702]

136. Pascual A, Henry M, Briolant S et al. In vitro activity of Proveblue (methylene blue) on Plasmodium falciparum strains resistant to standard antimalarial drugs. Antimicrob Agents Chemother. 2011; 55:2472-4. [PubMed 21343466]

137. Vennerstrom JL, Makler MT, Angerhofer CK et al. Antimalarial dyes revisited: xanthenes, azines, oxazines, and thiazines. Antimicrob Agents Chemother. 1995; 39:2671-7. [PubMed 8593000]

138. Akoachere M, Buchholz K, Fischer E et al. In vitro assessment of methylene blue on chloroquine-sensitive and -resistant Plasmodium falciparum strains reveals synergistic action with artemisinins. Antimicrob Agents Chemother. 2005; 49:4592-7. [PubMed 16251300]

139. Meissner PE, Mandi G, Coulibaly B et al. Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J. 2006; 5:84. [PubMed 17026773]

140. Garavito G, Bertani S, Rincon J et al. Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum. Parasite. 2007; 14:135-40. [PubMed 17645185]

141. Porat R, Gilbert S, Magilner D. Methylene blue-induced phototoxicity: an unrecognized complication. Pediatrics. 1996; 97:717-21. [PubMed 8628613]

142. Sills MR, Zinkham WH. Methylene blue-induced Heinz body hemolytic anemia. Arch Pediatr Adolesc Med. 1994; 148:306-10. [PubMed 8130867]

143. George M. Methylene-blue-induced hyperbilirubinemia and phototoxicity in a neonate. Clin Pediatr (Phila). 2000; 39:659-61. [PubMed 11110367]

144. McEnerney JK, McEnerney LN. Unfavorable neonatal outcome after intraamniotic injection of methylene blue. Obstet Gynecol. 1983; 61(3 Suppl):35S-37S. [PubMed 6823393]

145. Crooks J. Haemolytic jaundice in a neonate after intra-amniotic injection of methylene blue. Arch Dis Child. 1982; 57:872-3. [PubMed 6890790]

146. Cowett RM, Hakanson DO, Kocon RW et al. Untoward neonatal effect of intraamniotic administration of methylene blue. Obstet Gynecol. 1976; 48(1 Suppl):74S-75S. [PubMed 945881]

a. AHFS Drug Information 2013. McEvoy GK, ed. Methylene Blue. Bethesda, MD: American Society of Health-System Pharmacists; 2013: .

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