A 77-year-old woman arrived at a Florida emergency department after a fall that broke her right wrist. During her workup, staff collected a urine sample. It was an unmistakable blue-green.
The most likely explanation, emergency physicians at the University of South Florida Morsani College of Medicine in Tampa reported in a case report in Cureus, was a pill she took to prevent urinary tract infections. It contained methylene blue, a dye that can tint urine blue or green.
The harmless-looking color has a less obvious side. Methylene blue also blocks an enzyme the brain uses to break down serotonin, which led the FDA to warn about serious reactions when the dye is given to people taking certain psychiatric medications. Her home medication list included drugs from that category.
A Fall, a Broken Wrist and a Surprising Urine Sample
According to the report by Carson Balen, Zayd Chishti and Jason W. Wilson, the woman fell from standing height at home without losing consciousness. She stayed alert and oriented on the way to the hospital, her vital signs were normal on arrival, and she had an open fracture of her right wrist that was later repaired surgically.
Her history included high blood pressure, high cholesterol, urinary retention, frequent urinary tract infections, and a prior kidney injury. She had a sacral nerve implant to help with urinary retention.
Her long list of home medications included Uro-MP, a combination product containing methenamine, sodium phosphate, phenyl salicylate, hyoscyamine and methylene blue. It also included the antidepressants duloxetine and bupropion and the anti-anxiety drug buspirone, among others.
Ruling Out Infection, Liver Trouble and Rare Genetic Disorders
Blue-green urine is uncommon and has received far less study than red, brown or yellow urine, the authors noted. Its possible causes range from harmless to serious.
One important cause is infection. The bacterium Pseudomonas aeruginosa produces a blue-green pigment called pyocyanin that can tint urine. A buildup of biliverdin, a green bile pigment, can also color urine in people with conditions that block bile flow. Rare inherited disorders such as Hartnup disease are another possibility. Several medications, including propofol, amitriptyline, indomethacin, cimetidine and promethazine, have also been linked to blue or green urine.
Her urinalysis showed no sign of infection, which the authors said ruled out Pseudomonas, and microscopy found normal white blood cell counts. She had no known history of the relevant genetic disorders or of the upper-right abdominal pain that might suggest a bile problem. After surgery, she was discharged with plans for clinic follow-up.
That left the dye. In the body, methylene blue is converted into a colorless form, but once it reaches the urine it can revert to its blue state, producing a blue-green hue. A letter in Annals of Laboratory Medicine from MD Anderson Cancer Center notes that after an oral dose, the dye peaks roughly two to six hours later and remains detectable at 24 hours. It can also interfere with some lab tests, including falsely raising methemoglobin readings.
That letter described a similar case: a 53-year-old man with prostate cancer whose urine turned blue-green from a methylene blue-containing medication prescribed for painful urination.
The Dye Also Acts on a Brain Enzyme
Methylene blue inhibits monoamine oxidase A, an enzyme that breaks down serotonin. In July 2011, the FDA issued a drug safety communication on methylene blue warning of serious central nervous system reactions when the dye was given to patients taking serotonergic psychiatric medications, a condition known as serotonin syndrome.
An updated FDA safety communication added important context. Most reported cases occurred during parathyroid surgery, when methylene blue was given intravenously at doses of 1 to 8 mg/kg. The agency said it was not known whether methylene blue given by other routes, such as by mouth, carries the same risk. The cases involved SSRIs, SNRIs and clomipramine. Duloxetine is an SNRI, while bupropion and buspirone appeared among drugs with lesser serotonergic activity, for which the agency called the risk unclear.
FDA labeling for methylene blue now carries a boxed warning about serotonin syndrome with serotonergic drugs, according to the StatPearls clinical reference.
The Cureus report does not describe any interaction-related problems in this patient, and the authors did not address the issue. Because the FDA said the risk from oral methylene blue was unknown, her case cannot settle that question either way.
Still, it highlights why a complete medication list matters, especially for older adults taking many prescriptions. Patients should not stop or change any medication on their own and can ask a pharmacist or prescriber to review their full list.
When a Strange Urine Color Deserves a Call
In this case, the color was a side effect rather than a sign of disease. The authors emphasized that a careful history and physical exam can often explain unusual urine colors without costly testing.
MedlinePlus, from the National Library of Medicine, lists artificial colors in foods or medicines, bilirubin, medicines including methylene blue, and urinary tract infections among causes of green or blue urine. It advises seeing a health care provider for any abnormal urine color that cannot be explained and does not go away, and for blood in the urine, even once.
Key Questions Answered
Why was the woman's urine blue-green?
Doctors concluded it most likely came from methylene blue in Uro-MP, a urinary tract infection prevention medication she took at home.
Is blue-green urine dangerous?
Often it is harmless and caused by dyes or medications, but it can also signal a Pseudomonas infection or other conditions, so unexplained color changes should be checked.
What is the concern with methylene blue?
It inhibits monoamine oxidase A. The FDA has warned about serotonin syndrome when methylene blue is given with certain serotonergic psychiatric medications, with most reported cases involving intravenous use during surgery.
Does oral methylene blue cause serotonin syndrome?
In 2011, the FDA said it was not known whether methylene blue given by mouth carries the same risk as intravenous doses.
What should people taking these medications do?
They should not stop or change medications on their own. A pharmacist or prescriber can review the full medication list for possible interactions.
Published by Medicaldaily.com
