- PRODUCT MONOGRAPH
Phenazopyridine Hydrochloride Tablets USP
100 and 200 mg
Urinary Tract Analgesic
- SUMMARY PRODUCT INFORMATION
Route of Administration | Dosage Form / Strength | Nonmedicinal Ingredients
oral Tablet 100 mg, 200 mg Carnauba wax, cornstarch, D&C red No. 7, FD&C blue No. 2, FD&C yellow No. 6, gelatin, lactose, magnesium stearate, methylcellulose, sodium starch glycolate, sucrose, titanium dioxide and white wax.
- INDICATIONS AND CLINICAL USE
Adults (≥18 years old):
PYRIDIUM® (Phenazopyridine Hydrochloride) is indicated for the symptomatic relief of pain, burning, urgency, frequency, and other discomforts resulting from irritation of the mucosa of the lower urinary tract caused by infection, trauma, surgery, endoscopic procedures, or the passage of sounds or catheters.
Phenazopyridine is compatible with antimicrobial therapy and can help relieve pain and discomfort during the interval before an antimicrobial therapy controls the infection.
Treatment with phenazopyridine should not exceed 2 days because of potential organ damage. (See Warnings and Precautions)
Geriatrics (>65 years old): No data are available
Pediatrics(< 18 years old): No data are available
PYRIDIUM® is contraindicated in:
- patients who are hypersensitive to the drug or its ingredients.
- patients with renal insufficiency or any liver disease.
- WARNINGS AND PRECAUTIONS
Serious Warnings and Precautions
A yellowish color of the skin or sclerae may indicate accumulation of phenazopyridine resulting from impaired renal function or overdose or taking the drug for more than two days, and necessitates discontinuance of the drug. It should be noted that a decline in renal function is common in elderly patients. Phenazopyridine produces an orange to red color in the urine and feces, and may cause staining. Phenazopyridine may cause discoloration of body fluids and staining of contact lenses. Phenazopyridine may mask pathological conditions and interfere with laboratory test values using colorimetric, spectrophotometric or fluorometric analysis methods.
Cautious use in patients with G-6-PD deficiency is advised since these patients are susceptible to oxidative hemolysis and may have greater potential to develop hemolytic anemia.
Patient Counselling by the physician:
- The patient should be advised to take phenazopyridine with or following food or after eating a snack to reduce stomach upset.
- The patient should be advised that phenazopyridine produces an orange to red color in the urine and feces, and may cause staining.
- The patient should be advised that treatment with Pyridium should not exceed 2 days.
- The patient should be advised to discontinue Pyridium and contact their doctor immediately if they notice a yellowish color of the skin or sclerae (white of the eye).
Carcinogenesis and Mutagenesis
Long-term administration of phenazopyridine has been associated with tumors of the large intestine in rats and of the liver in mice. Available epidemiological data are insufficient to evaluate the carcinogenicity of phenazopyridine in humans. In vitro studies indicate that phenazopyridine in the presence of metabolic activation is mutagenic in bacteria and mutagenic and clastogenic in mammalian cells.
Treatment with phenazopyridine should not exceed 2 days. 2,3,6-triaminopyridine, a metabolite of phenazopyridine, caused extensive injury to the skeletal muscle and, to a lesser extend, the heart muscle in rats in a toxicology study. Caution is advised when giving phenazopyridine to patients with a heart condition or to patients with any neuromuscular condition.
Phenazopyridine is contraindicated in patients with any liver disease. (See Contraindications)
Phenazopyridine is contraindicated in patients with renal insufficiency. The decline in renal function associated with advanced age should be kept in mind. There are no data available in elderly patients.
Phenazopyridine produces an orange to red color in the urine (See Serious Warnings and Precautions).
Patients with G-6-PD deficiency are susceptible to oxidative hemolysis and may have greater potential to develop hemolytic anemia (See Serious Warnings and Precautions). Phenazopyridine should not be used in patients with G-6-PD Mediterranean as hemolysis may occur at normal doses in these patients.
The use of phenazopyridine for relief of symptoms should not delay definitive diagnosis and treatment of causative conditions. The drug should be used for symptomatic relief of pain and not as a substitute for specific surgery or antimicrobial therapy.
A yellowish color of sclerae (white of the eye) may indicate accumulation of phenazopyridine resulting from impaired renal function or overdose or taking for more than two days, and necessitates discontinuance of the drug. (See Serious Warnings and Precautions).
A yellowish color of the skin may indicate accumulation of phenazopyridine resulting from impaired renal function or overdose or taking for more than two days, and necessitates discontinuance of the drug. (See Serious Warnings and Precautions).
Reproductive studies with phenazopyridine (in combination with sulfacytine) in rats given up to 110 mg/kg/day and in rabbits given up to 39 mg/kg/day during organogenesis revealed no evidence of harm to offspring.
One very limited prospective study in humans demonstrated that phenazopyridine traverses the placenta into the fetal compartment. There are no adequate and well-controlled studies in pregnant women. Therefore, phenazopyridine should be used in pregnant women only if the benefit clearly outweighs the risk.
It is unknown if the drug is excreted in human milk. Because many drugs are excreted in human milk precaution should be exercised.
Pediatrics ( 65 years old)
Safety and effectiveness in elderly patients above 65 have not been established.
- ADVERSE REACTIONS
Adverse Drug Reaction Overview
- Gastrointestinal: nausea, vomiting and diarrhea.
- Nervous System: headache, aseptic meningitis.
- Integumentary: rash, pruritus, discoloration, jaundice,.
- Renal: renal toxicity usually associated with overdose, renal calculi.
- Hematologic: methemoglobinemia, hemolytic anemia, potential hemolytic agent in G-6-PD deficiency, sulfhemoglobinemia, neutropenia, leukopenia, pancytopenia.
- Body as a Whole: anaphylactoid-like reaction and hypersensitivity hepatitis.
- Special Senses: visual disturbances, eye irritation, ear pain, reversible loss of color vision.
- Other: hepatic toxicity usually associated with overdose, discoloration of body fluids.
- DRUG INTERACTIONS
The medical literature suggests that no significant interactions have been reported besides the one mentioned below.
Table 1 Established or Potential Drug-Drug Interactions (SEE TABLE IN PDF VERSION)
Drug-Laboratory Test Interactions
Due to its properties as an azo dye, Phenazopyridine HCl may interfere with urinalysis based on spectrometry or color reactions (See Warnings and Precautions).
Phenazopyridine may interfere with the phenolsulfonphthalein (PSP) excretion test of kidney function; butanol may be used to extract phenazopyridine from the final alkaline urine dilution to give accurate results.
Phenazopyridine may interfere with urinary glucose tests. Phenazopyridine may interfere with urinary ketone tests using sodium nitroprusside or Gerhardt ferric chloride by producing interfering colors. Phenazopyridine may interfere with urinary urobilinogen determinations because of color interference with Ehrlich’s reagent. Phenazopyridine may produce falsely elevated readings in the spectrophotofluorimetric screening tests and assays for porphyrins.
Phenazopyridine may interfere with laboratory test values using colorimetric, photometric or fluorometric analysis methods. Altered urine laboratory test values may include ketone (sodium nitroprusside), bilirubin (foam test, talc-disk-Fouchet-spot test, Franklin's tablet-Fouchet test, p-nitrobenzene diazonium p-toluene sulfonate reagent), diacetic acid (Gerhardt ferric chloride test), free hydrochloric acid, glucose (glucose oxidase tests), 17-hydroxycorticosteroids (modified Glenn-Nelson), 17-ketosteroids (Holtorff Koch modification of Zimmerman), porphyrins, albumin (discolors bromophenol blue test areas of commercial reagent strips, nitric acid ring test), phenolsulfophthalein, urobilinogen (color interference with Ehrlich's reagent), and urinalysis (spectrophotometric or color-based tests). Phenazopyridine also imparts an orange-red color to stools which may interfere with color tests.
- DOSAGE AND ADMINISTRATION
Recommended Dose and Dosage Adjustment
Adults: 200 mg 3 times daily after meals.
When used concomitantly with an antibacterial agent for the treatment of a urinary tract infection, the administration of phenazopyridine should not exceed 2 days. If symptoms persist, the patient should be re-evaluated.
If a dose is missed, patients should take it as soon as they remember. If it is near the time of the next dose, patients should skip the missed dose and resume their usual dosing schedule. Patients should not double the dose to catch up.
Administration is by the oral route, preferably after meals.
For management of a suspected drug overdose contact your regional Poison Control Centre.
Exceeding the recommended dose in patients with normal renal function or administering the recommended dose to patients with reduced renal function (common in elderly patients) may lead to increased serum levels and toxic reactions.
Methemoglobinemia generally follows a massive, acute overdose. Oxidative Heinz body hemolytic anemia also may occur, and “bite cells” (degmacytes) may be present in a chronic overdosage situation. Red blood cell G-6-PD deficiency may predispose to hemolysis; however, hemolysis may occur at normal doses in patients with G-6-PD Mediterranean. Renal toxicity and occasional failure and hepatic impairment may also occur.
Treatment: Treatment is symptomatic and supportive. Methylene blue, 1 to 2 mg/kg/dose given i.v. as a 1% solution as needed, should cause prompt reduction of the methemoglobinemia and disappearance of the cyanosis which is an aid in diagnosis.
- ACTION AND CLINICAL PHARMACOLOGY
Mechanism of Action
Phenazopyridine is excreted in the urine where it exerts a topical analgesic effect on the mucosa of the lower urinary tract. This action helps to relieve pain, burning, urgency and frequency. The precise mechanism of action is unknown.
The pharmacokinetic properties of phenazopyridine have not been fully elucidated. Phenazopyridine and its metabolites are rapidly excreted by the kidneys. In a small number of healthy subjects, 90% of a 600 mg/day oral dose of phenazopyridine was eliminated in the urine in 24 hours, 41% as unchanged drug and 49% as metabolites.
STORAGE AND STABILITY
Store at controlled room temperature, 15-30oC.
- DOSAGE FORMS, COMPOSITION AND PACKAGING
PYRIDIUM® 100 mg: Each reddish brown, coated tablet, imprinted with a white PD 180 monogram on one side, contains: phenazopyridine HCl 100 mg. Nonmedicinal ingredients: carnauba wax, cornstarch, D&C red No. 7, FD&C blue No. 2, FD&C yellow No. 6, gelatin, lactose, magnesium stearate, methylcellulose, sodium starch glycolate, sucrose, titanium dioxide and white wax. Energy: 1.76 kJ (0.42 kcal)/100 mg. Sodium: 0.32 mg. gluten-, paraben-, sulfite- and tartrazine-free. Bottles of 100.
PYRIDIUM® 200 mg: Each reddish brown, coated tablet, imprinted with a white PD 181 monogram on one side, contains: phenazopyridine HCl 200 mg. Nonmedicinal ingredients: carnauba wax, cornstarch, D&C red No. 7, FD&C blue No. 2, FD&C yellow No. 6, gelatin, lactose, magnesium stearate, methylcellulose, sodium starch glycolate, sucrose, titanium dioxide and white wax. Energy: 3.52 kJ (0.84 kcal)/200 mg. Sodium: 0.32 mg. gluten-, paraben-, sulfite- and tartrazine-free. Bottles of 100.
- PHARMACEUTICAL INFORMATION
- Proper Name: Phenazopyridine hydrochloride
- Chemical Name: 2, 6-pyridinediamine, 3-(phenylazo)-, monohydrochloride.
- Empirical Formula: C11H11N5 HCl
- Molecular Weight: 249.70
- Structural Formula:
- DETAILED PHARMACOLOGY
Phenazopyridine Hydrochloride exerts a topical analgesic effect on the mucosa of the lower urinary tract. This
action helps to relieve pain, burning, urgency and frequency. The precise mechanism of action is not known.
Phenazopyridine HCl is rapidly excreted by the kidneys, with as much as 65% of an oral dose being excreted
unchanged in the urine.
Toxic reactions to phenazopyridine, an azo dye, appear to be rare. Metabolism of phenazopyridine results in the
formation of large quantities of aniline, and the production of methemoglobinemia by phenazopyridine is
probably due to the aniline metabolites. Because the azo dye is deposited in the skin, yellow skin pigmentation
has been noted in cases of azo dye intoxication.
The oral administration of phenazopyridine hydrochloride to dogs showed that the drug accumulated selectively in lacrimal and nictitans glands and the glands of Moll, and caused a reduction of tear flow. The drug or its metabolic derivative was detectable by light microscopy as an accumulation in the cytoplasm within 48 hours after drug administration. Electron microscopy showed that the product detected was localized in secretory granules. The results suggest that phenazopyridine hydrochloride affects the synthesis of secretory granules and causes progressive destruction of affected cells.
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