Phenazopyridine (pyridium, AZO) - yet another example of missing research

Phenazopyridine is an old drug, discovered in the 1930s. Chemically it’s classified as an “azo dye”, these chemicals are usually used to color clothing. Phenazopyridine will stain clothing orange. Another Azo dye was once used a seizure med. 

Two-thirds of a dose is excreted unchanged in the urine (and sweat and tears), the rest is metabolized to unknown substances. It has some sort of anesthetic action on the urinary tract, we don’t know how that works. “Trace amounts” may enter the cerebrospinal fluid. With prolonged use there is injury to both liver and kidney.

Historically phenazopyridine was prescribed for use in the very early stages of a bladder infection, before antibiotics did their job (since it’s older than antibiotics I suspect it was used heavily in the past). It’s over the counter now, to be used for one to two days.

Except some patients use phenazopyridine for longer than a few days. Interstitial cystitis is particularly nasty syndrome. Like many poorly understood disorders (osteoarthritis, autism, etc) it’s probably several different disorders that share common features. One pattern of interstitial cystitis causes severe sleep disruption; patients wake up to void every 10 to 60 minutes with very small volume urination. On bladder biopsy the protective lining of the bladder has been disrupted. 

Sleep deprivation is a well understood and effective form of torture, so it’s not surprising that IC patients get a bit desperate (you would too). Phenazopyridine may allow sleep when all else fails. So it’s used more than it should be, especially since it’s available without a prescription.

Since phenazopyridine has an anesthetic effect, we presume it interacts with the peripheral nervous system.  So what happens to the brain with large lifetime doses of phenazopyridine? I can’t see that this has ever been investigated, even in animal models.  Tartrazine, another azo dye used in food coloring, was associated with oxidative brain damage in one rat study.

Medicine is full of things like phenazopyridine. Medications that were adopted long ago, and have received minimal research review since. We could employ an army of scientists studying these drugs. But then we’d have to figure out how to pay for them…