What are the side effects of taking methylene blue orally?

Side Effects of Oral Methylene Blue

Oral methylene blue can cause green discoloration of urine and stool, and in rare cases may precipitate serotonin syndrome when used with serotonergic medications, particularly at higher doses. 1

Common Side Effects

Methylene blue when taken orally has several documented side effects:

• Gastrointestinal effects:

  • Discoloration of stool (green hue) 1
  • Nausea 2
  • Diarrhea 2
  • Abdominal pain 2
  • Dry mouth 2

• Urinary effects:

  • Green discoloration of urine (persists up to 24 hours) 1

• Neurological effects:

  • Headache 2
  • Dizziness 2
  • Paresthesia 2

Serious Side Effects

While rare with oral administration, more serious side effects can occur, especially at higher doses:

1. Serotonin syndrome: Methylene blue is a monoamine oxidase inhibitor (MAOI) that can interact with serotonergic medications 3, 4. This can manifest as:

   • Neuromuscular hyperactivity
   • Confusion
   • Agitation
   • Seizure-like phenomena 2

2. Cardiovascular effects:

   • Hypertension 5
   • Palpitations 2
   • Tachycardia 2

3. Hematologic effects:

   • Risk of hemolysis, particularly in patients with G6PD deficiency 1, 5
   • Potential for methemoglobinemia at very high doses 2

Special Populations and Precautions

G6PD Deficiency

Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency should avoid methylene blue as it can cause significant hemolytic anemia 1.

Patients on Serotonergic Medications

Patients taking selective serotonin reuptake inhibitors (SSRIs) or other serotonergic medications should avoid methylene blue due to the risk of serotonin syndrome 3, 4.

Pregnancy

Methylene blue should be used with caution in pregnant women due to concerns about potential teratogenicity 1, 2.

Renal Impairment

Patients with renal impairment may experience increased methylene blue concentrations and should be monitored for toxicity 2.

Hepatic Impairment

Since methylene blue is extensively metabolized in the liver, patients with hepatic impairment should be monitored for extended periods following treatment 2.

Dosage Considerations

The risk of side effects appears to be dose-related 6, 5. When used as a food dye during swallowing assessments in small amounts, serious adverse events are rare (0.16%) 6.

Clinical Context

It's worth noting that while methylene blue has been used for various clinical applications including as a diagnostic aid and for treating methemoglobinemia, its oral use requires careful consideration of potential side effects, especially at higher doses or in vulnerable populations 7, 5.