Methemoglobinemia from prolonged therapeutic use of phenazopyridine
Annals of Clinical Case Reports
Published: 19 Aug, 2016
Methemoglobinemia from Prolonged Therapeutic Use of
Williamson K*, Htet N and Nanini S
Department of Emergency Medicine, Advocate Christ Medical Center, USA
Background: Phenazopyridine is often prescribed for patients suffering from urinary tract
infections as its local analgesic properties can provide immediate symptomatic improvement. It is
classically taken for two days while awaiting antibiotic effect. It is available without a prescription in
the United States under the trade names: Azo Urinary Pain Relief, Uricalm, and Uristat. Common
adverse reactions include urine discoloration, rash, pruritus, nausea, dyspepsia, and headache.
Phenazopyridine has been reported to cause methemoglobinemia in overdose, though rarely with
Case Report: We report a case of an 82-year-old woman who had been taking phenazopyridine at a
therapeutic dose for three months when she presented to emergency department with hypoxia. Arterial
blood gas revealed a methemoglobinemia level of 15%. Patient's hypoxia corrected with administration
of methylene blue. Why should an emergency physician be aware of this?: Phenazopyridine toxicity,
most commonly reported with acute overdose, can lead to methemoglobinemia by converting the
iron molecule in hemoglobin to methemoglobin. Administration of methylene blue is typically
curative. This case highlights the importance of considering methemoglobinemia in patients who
present with hypoxia while taking phenazopyridine.
Keywords: Methemoglobinemia; Phenazopyridine; Hypoxia; Methylene blue
Methemoglobinemia refers to a disorder characterized by abnormal levels of methemoglobin in
the blood resulting from the oxidation of iron in hemoglobin from the ferrous (Fe2+) to ferric (Fe3+)
form. The oxidized ferric group has an impaired ability to bind oxygen; in addition, oxygen affinity
for any remaining ferrous hemoglobin is increased, thereby shifting the oxygen dissociation curve to
the left. As a result, oxygen cannot be appropriately released, leading to tissue hypoxia .
Kelly Williamson, Department of
While there are several congenital causes, methemoglobinemia is most commonly caused
Emergency Medicine at Advocate Christ
by medications that contain oxidizing chemicals such as nitrites, nitroglycerin, nitroprusside,
Medical Center, 4440 West 95th Street,
trimethoprim/ sulfamethoxazole, inhaled nitrous oxide, and aniline derivatives .
185W, Oak Lawn, Illinois 60453, USA,
Tel: (708) 684-5354, (434) 466-2969,
Phenazopyridine has been described in the literature as an agent causing methemoglobinemia,
hemolytic anemia and renal failure in the adult and pediatric overdose situation [2-8], and in the
Received Date: 18 Jul 2016
therapeutic usage in patients with renal impairment . Few case reports describe the development
Accepted Date: 14 Aug 2016
of methemoglobinemia at therapeutic doses in patients with normal renal function [10-12], though
Published Date: 19 Aug 2016
no similar cases have been reported in the emergency medicine literature.
Since phenazopyridine is available without a prescription, it is essential that emergency
Williamson K, Htet N, Nanini S.
physicians appropriately recognize the adverse reaction of methemoglobinemia in patients taking
Methemoglobinemia from Prolonged
urinary anesthetics. A case of an 82-year-old woman with a methemoglobinemia level of 15% from
Therapeutic Use of Phenazopyridine.
prolonged use of phenazopyridine is reported.
Ann Clin Case Rep. 2016; 1: 1085.
Copyright 2016 Williamson K. This is
An 82-year-old woman presented to the emergency department by ambulance for hypoxia.
an open access article distributed under
Patient had no known pre-existing cardiac or pulmonary conditions. During routine vitals
the Creative Commons Attribution
assessment at her assisted living facility, the patient's pulse oximeter was noted to be 83%. She
License, which permits unrestricted
received albuterol without improvement in the pulse oximeter reading, and transferred to the
use, distribution, and reproduction in
emergency department for further evaluation. Paramedics put the patient on 15 liters of oxygen via
any medium, provided the original work
a non-rebreather for transport.
is properly cited.
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2016 Volume 1 Article 1085
Williamson K, et al.
Annals of Clinical Case Reports - Emergency Medicine
On arrival to emergency department, the patient denied chest oxygen administration with anecdotal success  and N-acetyl
pain or shortness of breath. Past medical history was significant cysteine, though a randomized controlled trial demonstrated no
for multiple sclerosis and deep vein thrombosis; patient also had a
reduction in methemoglobin levels [13,14].
chronic indwelling Foley catheter. Medications included warfarin
4.5mg once a day, baclofen 10mg as needed and phenazopyridine
In the case described above, the patient was on prolonged use of
200mg three times a day. Patient began taking phenazopyridine three
phenazopyridine and presented with hypoxia on pulse oximeter but
months prior to presentation for urinary irritation secondary to the
a normal oxygen level on ABG; the methemoglobin level was 15% on
indwelling Foley catheter.
co-oximeter. This patient received intravenous methylene blue and
achieved normalization of the level within minutes.
On general examination, the patient was well appearing. The vital Conclusion
signs were: temperature 36.7'C, blood pressure 146/62 mmHg, pulse
77bpm, respiratory rate 18/min, and oxygen saturation of 92% on 15L
The diagnosis of methemoglobinemia is a time-sensitive
oxygen via a non-rebreather. The patient appeared mildly cyanotic. emergency. As therapeutic use of over-the-counter phenazopyridine
Cardiovascular and pulmonary examinations are unremarkable. The may result in methemoglobinemia, emergency physicians must
urinary catheter was in place with orange colored urine in the bag. consider this adverse reaction in patients who present with cyanosis
The remainder of the physical examination was unremarkable.
Arterial blood gas with co-oximeter was obtained with the References
following results: pH 7.44, pCO 44, pO 461, HCO 28, O sat 98,
Carbon monoxide 3.1, O content arterial 10, OxyHemoglobin 80.8%,
Methemoglobin 14.9 %on15L oxygen via non-rebreather.
On further laboratory testing, electrolytes and kidney function 2.
were unremarkable, as were the troponin and B-type natriuretic
peptide. Complete blood count results were WBC 8.4 with normal
differential, Hemoglobin 8.5, Hematocrit 27.9, MCV 99, MCH 30.4,
MCHC 30.5, RDW 18.7, and Platelet 269.The INR was 2.2.
The patient received IV methylene blue 1mg/kg for a total dose
of 80mg and within minutes her pulse oximeter improved to 98% on
room air. The patient was observed in the hospital for 24 hours and
had no further episodes of hypoxia. She was then discharged back to 5.
her assisted living facility.
Phenazopyridine is utilized for its local anesthetic properties in
patients suffering from urinary tract infection, though its use should
be limited to 48 hours and discontinued after appropriate antibiotics 7.
have lessened symptoms. In the case presented, a patient developed
toxicity from a therapeutic dose of phenazopyridine for a prolonged
Methemoglobinemia can develop from medications that lead
to the oxidation of the iron molecule in hemoglobin. In healthy
individuals, a reducing enzyme cascade converts methemoglobin
back to hemoglobin. In the case of phenazopyridine toxicity, the
reduction cascade is overwhelmed, leading to the accumulation of
Patients with methemoglobinemia can present with hypoxia or
cyanosis, though the PaO2 on arterial blood gas is normal. Patients
may be asymptomatic at low levels, but may experience fatigue,
headache, dizziness, tachycardia, weakness, dyspnea, bradycardia, 12.
seizures, coma, and death at progressively higher levels . Treatment
is determined by associated symptoms and may range from
discontinuing the offending medication in a minimally symptomatic 13.
patient with a low methemoglobin level to administration of
intravenous methylene blue at a dose of 1-2mg/kg over 5 minutes
with a repeated dose in 1 hour if the level remains high. If a patient
presents in shock, then blood transfusion or exchange transfusion
may be initiated. Additional therapies have included hyperbaric
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2016 Volume 1 Article 1085
Doxycycline and osteoarthritis: what does it show us? Original article Brandt KD et al. (2005) Effects of pain and function were used as secondary doxycycline on progression of osteoarthritis. Results of a outcome measures. randomized, placebo-controlled, double-blind trial. Arthritis Rheum 52: 2015–2025
29th International Cosmic Ray Conference Pune (2005) 00, 101–104 Observation of AGNs with PACTBose D. , Acharya B.S. , Chitnis V. R. , Singh B.B. , Vishwanath P. R.(a) Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India(b) Indian Institute of Astrophysics, Koramangala, Bangalore 560034, IndiaPresenter: Bose D. ([email protected]), ind-bose-D-abs1-og23-oral