Pyridium (Phenazopyridine) for Urinary Tract Pain
Recommended Adult Dosing
Phenazopyridine should be dosed at 200 mg orally three times daily after meals for symptomatic relief of urinary tract pain, with a maximum duration of 2 days when used alongside antibiotics. 1, 2
- The standard dose is 200 mg three times daily, though some sources describe use of 400 mg three times daily in specific circumstances 1
- Administration after meals helps minimize gastrointestinal side effects 1
Maximum Duration of Use
Treatment should not exceed 2 days when used concurrently with antibiotics for acute urinary tract infections. 1, 2
- The manufacturer specifications clearly limit duration to prevent accumulation and toxicity 1
- Extended use beyond 2 weeks significantly increases the risk of methemoglobinemia and other serious adverse effects 1, 2
- One case series documented safe use for radiation cystitis with >14-day supplies, but this represents off-label extended use that requires careful monitoring 2
Absolute Contraindications
Phenazopyridine is contraindicated in patients with renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or liver disease, G6PD deficiency, and known hypersensitivity to the drug. 3, 4, 5
- Renal impairment dramatically increases toxicity risk, with acute renal failure reported even after single 1,200 mg ingestion in a patient without preexisting kidney disease 3
- Patients with baseline kidney disease face exponentially higher risk of acute tubular necrosis and acute interstitial nephritis 3, 4
- G6PD deficiency predisposes to severe hemolytic anemia and methemoglobinemia 1, 5
- Pregnancy is an exclusion criterion in clinical protocols 5
Common and Serious Side Effects
The most common side effect is orange discoloration of urine, which is expected and harmless, but serious adverse effects include methemoglobinemia, hemolytic anemia, acute renal failure, and hepatotoxicity. 3, 1, 4
Expected Effects:
Serious Adverse Effects:
- Methemoglobinemia presents with refractory hypoxia (pulse oximetry 80s despite 100% FiO2), dusky/cyanotic skin, and chocolate-brown blood; levels >20% with symptoms or >30% regardless of symptoms require treatment with methylene blue 1-2 mg/kg IV or vitamin C if methylene blue is contraindicated 1
- Acute renal failure can manifest as acute tubular necrosis or acute interstitial nephritis, occurring even with therapeutic doses 3, 4
- Hemolytic anemia particularly in G6PD deficiency 3, 1
- Hepatotoxicity with elevated liver enzymes 4
Critical Clinical Pitfalls
Never prescribe phenazopyridine without verifying renal function first, as even single therapeutic doses can cause irreversible kidney injury in patients with unrecognized renal impairment. 3, 4
- Do not use phenazopyridine as monotherapy for urinary symptoms—it only masks pain and does not treat infection 6
- Avoid co-administration with serotonergic medications (MAOIs, SSRIs, SNRIs, TCAs) because if methemoglobinemia develops, first-line treatment with methylene blue can precipitate serotonin syndrome; use vitamin C instead 1
- Monitor for signs of methemoglobinemia (refractory hypoxia, cyanosis) especially when duration exceeds manufacturer recommendations 1
- Discontinue immediately if jaundice, dark urine beyond expected orange color, or signs of hemolysis appear 3, 4
Special Monitoring Considerations
Patients receiving phenazopyridine for >2 days require baseline and periodic monitoring of renal function, complete blood count, and liver enzymes. 4, 2
- Obtain baseline metabolic panel with creatinine clearance calculation before prescribing 5
- For extended use (>14 days, off-label), serial monitoring showed low overall adverse event rates (7.2% in one cohort), but vigilance for renal and hepatic toxicity remains essential 2
- Early recognition and drug discontinuation is the primary intervention; corticosteroids may improve recovery in acute interstitial nephritis cases 4