Medications and chemicals that may cause acquired methemoglobinemia

Medications

Amino salicylic acid (also called p-aminosalicylic acid or 4-aminosalicylic acid)

Clofazimine

Chloroquine

Dapsone

Local anesthetics, topical sprays and creams including benzocaine (in teething rings and ointments), lidocaine, and prilocaine

Menadione

Metoclopramide

Methylene blue*

Nitroglycerin

Phenacetin

Phenazopyridine

Primaquine

Rasburicase^¶

Quinones

Sulfonamides

Foods and beverages

Frozen or dried foods that use nitrites or sodium nitrate as a preservative

Mushrooms

Root vegetables, leafy-green vegetables, other vegetables

Well water (contains nitrates)

Chemicals and environmental substances

Acetanilide (used in varnishes, rubber, and dyes)

Anilines and aniline dyes (eg, diaper and laundry marking inks, leather dyes, red wax crayons)

Antifreeze

Benzene derivatives (used as solvents)

Chlorates and chromates (used in chemical and industrial synthesis)

Hydrogen peroxide (used as a disinfectant and cleaner)

Naphthalene (used in mothballs)

Naphthoquinone (used in chemical synthesis)

Nitrates and nitrites (eg, amyl nitrite, farryl nitrite, sodium nitrite, nitric oxide). Sodium nitrate is used as a food curing salt and has been ingested during suicide attempts.

Nitrogen-based fertilizers (runoff)

Nitrobenzene (used as a solvent)

Paraquat (used in herbicides)

Resorcinol (used in resin melting and wood extraction)

Refer to UpToDate topics on methemoglobinemia for additional details regarding these medications and chemicals, as well as citations with supporting evidence for their role in causing methemoglobinemia. Genetic/heritable causes of methemoglobinemia include M hemoglobins and cytochrome b5-reductase deficiency (the latter is extremely rare).

G6PD: glucose-6-phosphate dehydrogenase.

* While methylene blue is a recognized treatment for methemoglobinemia, it also has oxidant potential and may worsen the clinical status of individuals with G6PD deficiency because it induces acute hemolysis that can further decrease oxygen delivery to the tissues. In high doses, methylene blue can paradoxically increase methemoglobinemia.

¶ Risk of methemoglobinemia with rasburicase is especially high in individuals with G6PD deficiency; rasburicase should be avoided in these individuals.

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Medications and chemicals that may cause acquired methemoglobinemia