What medications can cause a change in urine color?

Medications That Change Urine Color

Rifamycin antibiotics (rifampin, rifabutin, rifapentine) universally cause orange discoloration of urine and all body fluids, while phenazopyridine produces reddish-orange urine, and metronidazole can cause dark brown or cola-colored urine in rare cases.

Rifamycin Antibiotics (Orange Discoloration)

Rifampin

• Causes universal orange discoloration of all body fluids including urine, sweat, tears, and sputum 1
• This effect occurs in 100% of patients taking the medication 2
• Patients must be warned before starting therapy that this discoloration is expected and benign 1
• Soft contact lenses and clothing may be permanently stained 1, 2

Rifabutin

• Produces identical orange discoloration of body fluids (urine, sputum, sweat, tears) as rifampin 1
• This is a universal effect occurring in all patients 1
• Can permanently stain soft contact lenses 1
• Patients should receive counseling about expected discoloration before treatment initiation 1

Rifapentine

• Causes the same orange discoloration pattern as other rifamycins 1
• This effect is consistent across the entire drug class 1

Phenazopyridine (Reddish-Orange Discoloration)

• Produces reddish-orange discoloration of urine as its primary and expected effect 3
• This is the mechanism by which the drug provides symptomatic relief for urinary tract discomfort 3
• Patients must be informed that this discoloration will occur and may stain fabric 3
• Contact lens staining has been reported 3
• The yellowish tinge of skin or sclera indicates drug accumulation from impaired renal excretion and requires discontinuation 3

Metronidazole (Dark Brown/Cola-Colored Urine)

• Causes darkened urine in approximately 1 in 100,000 patients, making this a rare but documented side effect 4
• The pigment responsible is almost certainly a metabolite of metronidazole 4
• Urine may appear dark brown or cola-colored 5, 6
• This discoloration has no clinical significance and causes no harm to the patient 4, 5
• When metronidazole is stopped, urine color returns to normal within 24-34 hours 5, 6
• Restarting the medication causes the dark color to recur 5

Other Medications Causing Urine Discoloration

Hydroxocobalamin (Red/Purple Urine)

• Causes reddish discoloration of urine that can mimic hematuria 7, 8
• When combined with methylene blue, can produce purple urine 7
• This is a benign effect that should not prompt unnecessary hematuria workup 8

Methylene Blue (Blue/Green Urine)

• Produces blue or green urine discoloration 7
• Can combine with other pigmented medications to create unusual colors 7

Clinical Pitfalls to Avoid

• Do not confuse medication-induced urine discoloration with hematuria or myoglobinuria 2, 8
• Orange urine from rifamycins should not trigger unnecessary hematuria evaluation 2
• Dark urine from metronidazole should be distinguished from hemolysis or rhabdomyolysis by checking appropriate laboratory tests if clinically indicated 5
• Red urine from hydroxocobalamin mimics hematuria but urinalysis will be negative for blood 8
• Phenazopyridine interferes with urinalysis based on spectrometry or color reactions, making interpretation unreliable 3