What medications can cause urine to turn red?

Medications That Cause Red Urine Discoloration

Phenazopyridine and metronidazole are the primary medications that cause red urine discoloration, with phenazopyridine producing a characteristic reddish-orange color and metronidazole causing darkened or reddish urine in rare cases.

Primary Causative Agents

Phenazopyridine (Most Common)

• Phenazopyridine produces a universal reddish-orange discoloration of urine as its most characteristic side effect 1
• This discoloration occurs in essentially all patients taking the medication and is completely expected 1
• The FDA label explicitly states that patients must be informed that phenazopyridine produces a reddish-orange discoloration of the urine and may stain fabric 1
• Contact lens staining has been reported, requiring specific patient counseling 1
• The mechanism involves the drug's properties as an azo dye, which can interfere with urinalysis based on spectrometry or color reactions 1

Metronidazole (Rare but Documented)

• Metronidazole can cause darkened urine in approximately 1 in 100,000 patients, though this is poorly recognized by many clinicians 2
• The FDA label describes instances of darkened urine, noting the pigment is almost certainly a metabolite of metronidazole with no clinical significance 2
• Case reports document cola-colored or reddish urine discoloration that resolves within 24-34 hours of discontinuing the medication and recurs upon rechallenge 3, 4
• The Naranjo probability scale assessment confirms metronidazole as the probable cause when other etiologies are excluded 3

Important Clinical Distinctions

Differentiation from Pathologic Causes

• True hematuria (blood in urine) must be distinguished from medication-induced discoloration through microscopic urinalysis 5
• Hematuria shows red blood cells on microscopic examination, while medication-induced discoloration does not 5
• Other pathologic causes of red urine include myoglobinuria from rhabdomyolysis, which requires different management 6

Related Discolorations (Not Red)

• Rifampicin causes orange (not red) discoloration of all body fluids universally 6
• Methylene blue causes green urine discoloration, which is entirely different from red urine 7

Critical Clinical Considerations

Patient Counseling Requirements

• Patients must be warned before starting phenazopyridine that reddish-orange urine is expected and will stain clothing and contact lenses 1
• For metronidazole, while rare, patients should be reassured if darkened urine occurs that it has no clinically relevant adverse outcomes 3

When to Investigate Further

• A yellowish tinge of skin or sclera with phenazopyridine may indicate drug accumulation from impaired renal excretion and requires discontinuation 1
• Advanced age increases risk due to declining renal function 1
• If urine discoloration is accompanied by systemic symptoms, investigate for serious complications like acute interstitial nephritis (phenazopyridine) or hemolytic anemia 8, 9

Toxicity Monitoring

• Phenazopyridine can cause acute kidney injury through multiple mechanisms including acute interstitial nephritis, acute tubular necrosis, and methemoglobinemia 8, 9
• Clinicians should monitor for signs of renal insufficiency when prescribing phenazopyridine, particularly in patients with preexisting kidney disease 8