What are the effects of oral methylene blue (methylthioninium chloride) administration on the body?

From the Guidelines

Methylene blue taken orally is primarily used to treat methemoglobinemia, a condition where an abnormal amount of methemoglobin is produced in the blood, at doses of 100-300 mg per day, as it converts methemoglobin back to normal hemoglobin, restoring oxygen-carrying capacity. The medication works by accepting an electron from NADPH and reducing the 3+ ferric state back to the 2+ ferrous state in erythrocytes 1.

Key Uses and Considerations

• Methylene blue has been used off-label as an antimicrobial agent, particularly for urinary tract infections, typically at doses of 100-200 mg 2-3 times daily.
• It also functions as a monoamine oxidase inhibitor at low doses (0.5-1 mg/kg), potentially helping with conditions like depression or anxiety.
• The medication can cause temporary blue-green discoloration of urine and feces, and may interfere with pulse oximeter readings.
• Caution is necessary as methylene blue can cause serotonin syndrome when combined with serotonergic medications, and is contraindicated in patients with G6PD deficiency, as it may induce hemolytic anemia in these patients 1.
• For any medical use, methylene blue should only be taken under direct medical supervision, as improper use can lead to serious side effects including hemolytic anemia.

Administration and Dosage

• The usual dose of methylene blue for treating methemoglobinemia is 1-2 mg/kg, which can be repeated if symptoms do not resolve within 30 minutes 1.
• In cases of congenital methemoglobinemia, oral methylene blue 100-300 mg per day may be administered, with dose adjustment according to MetHb levels 1.
• Ascorbic acid may also be used to treat methemoglobinemia, given in varying dosing regimens, from 0.2-1.0 g/day orally in divided doses 1.

Important Warnings and Precautions

• Methylene blue should be used with caution in pregnant women, patients with renal failure, and anesthetized patients, as it may cause teratogenicity, intestinal atresia, or inhibit guanylate cyclase, leading to systemic and pulmonary hypertension 1.
• Patients with a history of G6PD deficiency or those taking serotonergic medications should be closely monitored for potential adverse effects.

From the Research

Effects of Oral Methylene Blue Administration

• Methylene blue (MB) is used as a diagnostic substance and for the treatment of several diseases, including methemoglobinemia, vasoplegic syndrome, and cyanide intoxication 2.
• The administration of MB can have potential risks, including severe adverse effects such as hemolysis, methemoglobinemia, nausea, vomiting, chest pain, dyspnea, and hypertension 2.
• MB can induce serotonin syndrome, especially when used in conjunction with other serotonergic agents, which can be potentially lethal 3, 4, 5.
• The toxic effects of MB are dose-dependent, and oral administration of MB can also induce serotonin syndrome, although previous reports have exclusively been associated with parenteral administration 5.

Safety of Oral Methylene Blue

• A systematic review of the literature found that serious adverse events due to oral administration of MB are rare, with only three reported cases in a pooled population of 1902 patients 6.
• Non-serious adverse events related to oral MB administration are usually mild and self-limiting, and show a dose-related trend 6.
• The use of small amounts of MB as a food dye during swallowing examinations is considered safe, with a low risk of serious adverse events 6.