Are Methylene Blue Infusions Safe?

methylene blue and a syringe

The Bottom Line

Methylene blue is the antidote for a serious disease called methemoglobinemia but has also been studied for other medical uses. Since it has significant side effects and may interact with many medications, the routine use of methylene blue should be avoided.

Nurse adjusting an IV

The Full Story

Methylene blue is a chemical that was initially manufactured in 1876 as a textile dye. It was later studied as a medicinal therapy and was the first synthetic, or man-made, medical treatment used in humans. Initially used as an antiseptic, methylene blue was subsequently prescribed as a treatment for malaria and gonorrhea. Today, methylene blue is still used as a stain or dye, but it is likely best known as the antidote for a serious and life-threatening medical condition called methemoglobinemia. In methemoglobinemia, blood is not able to effectively carry oxygen to tissues, and affected patients have signs and symptoms of oxygen deprivation including blue-tinged skin, fatigue, and shortness of breath. Methylene blue is also used to treat toxic effects of certain chemotherapy drugs as well as circulatory shock, but it is not approved by the United States FDA for treatment of these conditions.

Methylene blue works on a cellular level within the mitochondria (the energy-producing powerhouses of cells) where it affects energy production and may also act as an antioxidant to protect cells against oxidative stress. Since oxidative stress is thought to hasten the aging process in humans, this means that methylene blue’s antioxidant effects may have some anti-aging activity. Methylene blue is also a photosensitizer, which means that it has increased activity when exposed to certain wavelengths of light. Light-activated methylene blue is used to treat donated blood products as it is effective in killing some viruses including HIV and herpes. Due to its antiviral activity, methylene blue has also been explored as a potential treatment for COVID-19. 

Because of its potential antiviral and anti-aging properties, some healthcare clinics offer methylene blue in formulations including skin creams and intravenous infusions to people who wish to increase longevity, stop the aging process, and prevent viral infections. While the use of methylene blue for these conditions sounds intriguing, it’s important to remember that methylene blue is currently approved by the United States FDA only for treatment of methemoglobinemia. It is not approved for the prevention or treatment of any other conditions. The use of methylene blue to prevent aging or to treat viral infections, including COVID-19, remains experimental at this time. There is no standard recommended human dosing for the use of methylene blue in conditions other than methemoglobinemia, and the potential health benefits of methylene blue for these other conditions have not been widely studied or described in medical literature.

As with all drugs, there are undesirable side effects associated with the use of methylene blue. Methylene blue administration can cause blue discoloration of urine and skin and can also cause dizziness, nausea, and headache. In high doses, methylene blue can actually cause methemoglobinemiathe exact condition it is intended to treat. Methylene blue can also have adverse interactions with several commonly used medications including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs). In 2017, the United States FDA issued a warning about the dangers of using methylene blue in patients who take these classes of medications. Since methylene blue can be harmful to a developing fetus, the drug should not be administered to pregnant women. Use of the drug should also be avoided by breastfeeding women. Because of methylene blue’s potentially toxic side effects (some of which can be life-threatening), people should only use methylene blue after consultation with a physician who has familiarity with the drug and its side effects. The routine use of intravenous methylene blue should be avoided, as the risks of the drug will likely outweigh any potential benefits.

If someone has developed unwanted signs or symptoms after exposure to methylene blue, get help online at webPOISONCONTROL or call 1-800-222-1222. Both options are free, confidential, and available 24 hours a day.

Kelly Johnson-Arbor, MD
Medical Toxicologist

Poisoned?

Call 1-800-222-1222 or

HELP ME online

Prevention Tips

  • Talk to your doctor before starting any new medications or nutritional supplements. All medications can potentially cause unwanted side effects.
  • There is no known cure for COVID-19. Vaccination is currently the best available method to prevent infection.
  • If you are pregnant or breastfeeding, talk with your doctor prior to taking over-the-counter medications, dietary supplements, or prescription drugs.

This Really Happened

A 29-year-old man with a history of cancer and depression was administered the chemotherapy drug ifosfamide (Ifex). He developed confusion and hallucinations and was diagnosed with chemotherapy-related toxicity. His symptoms improved after methylene blue was administered, and additional doses of methylene blue were prescribed to prevent additional chemotherapy-related toxicity. He then developed confusion, muscle rigidity, and sweating. These symptoms were initially attributed to the chemotherapy regimen but were later determined to be secondary to a drug interaction between methylene blue and venlafaxine (Effexor®), an antidepressant drug taken by the patient. The man required admission to the intensive care unit but eventually recovered without complications. 

For More Information

FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications (U.S. Food & Drug Administration)

Methylene Blue - Intravenous Route (Mayo Clinic)


References

Bachmann B, Knüver-Hopf J, Lambrecht B, Mohr H. Target structures for HIV-1 inactivation by methylene blue and light. J Med Virol. 1995 Oct;47(2):172-8.

Cagno V, Medaglia C, Cerny A, Cerny T, Zwygart AC, Cerny E, Tapparel C. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. Sci Rep. 2021 Jul 12;11(1):14295.

Gilbert B, Akamune IE. A Case of Serotonin Syndrome Caused by the Concomitant Utilization of Methylene Blue and Venlafaxine in an Oncological Patient. J Pharm Pract. 2020 Oct;33(5):705-707.

Gonzalez-Lima F, Auchter A. Protection against neurodegeneration with low-dose methylene blue and near-infrared light. Front Cell Neurosci. 2015 May 12;9:179.

Hajam YA, Rani R, Ganie SY, Sheikh TA, Javaid D, Qadri SS, Pramodh S, Alsulimani A, Alkhanani MF, Harakeh S, Hussain A, Haque S, Reshi MS. Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells. 2022 Feb 5;11(3):552.

Moore J. The Use of Methylene Blue in Gonorrhoea. Br Med J. 1897 Jan 16;1(1881):140.

Perrotta PL, Baril L, Tead C, Chapman J, Dincecco D, Buchholz DH, Snyder EL. Effects of methylene blue-treated plasma on red cells and stored platelet concentrates. Transfusion. 1999 Jan;39(1):63-9.

Pushparajah Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatr Emerg Care. 2021 Sep 1;37(9):474-477.

Saha BK, Burns SL. The Story of Nitric Oxide, Sepsis and Methylene Blue: A Comprehensive Pathophysiologic Review. Am J Med Sci. 2020 Oct;360(4):329-337.

Tardivo JP, Del Giglio A, de Oliveira CS, Gabrielli DS, Junqueira HC, Tada DB, Severino D, de Fátima Turchiello R, Baptista MS. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther. 2005 Sep;2(3):175-91.

Poisoned?

Call 1-800-222-1222 or

HELP ME online

Prevention Tips

  • Talk to your doctor before starting any new medications or nutritional supplements. All medications can potentially cause unwanted side effects.
  • There is no known cure for COVID-19. Vaccination is currently the best available method to prevent infection.
  • If you are pregnant or breastfeeding, talk with your doctor prior to taking over-the-counter medications, dietary supplements, or prescription drugs.

This Really Happened

A 29-year-old man with a history of cancer and depression was administered the chemotherapy drug ifosfamide (Ifex). He developed confusion and hallucinations and was diagnosed with chemotherapy-related toxicity. His symptoms improved after methylene blue was administered, and additional doses of methylene blue were prescribed to prevent additional chemotherapy-related toxicity. He then developed confusion, muscle rigidity, and sweating. These symptoms were initially attributed to the chemotherapy regimen but were later determined to be secondary to a drug interaction between methylene blue and venlafaxine (Effexor®), an antidepressant drug taken by the patient. The man required admission to the intensive care unit but eventually recovered without complications.