PYRIDIUM Tablet Ref.[10726] Active ingredients: Phenazopyridine

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.

Striated muscles

Treatment with phenazopyridine should not exceed 2 days. A metabolite of phenazopyridine (2,3,6- triaminopyridine) caused extensive injury to the skeletal muscle and, to a lesser extent, 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.

Hepatic/Biliary/Pancreatic

Phenazopyridine is contraindicated in patients with any liver disease. (See Contraindications).

Renal

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).

Hematologic

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.

Infection

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.

Ophthalmologic

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).

Skin

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).

Special Populations

Pregnant Women

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.

Nursing Women

It is unknown if the drug is excreted in human milk. Because many drugs are excreted in human milk, precaution should be exercised.

Pediatrics (<18 years old)

Safety and effectiveness in children below the age of 18 have not been established.

Geriatrics (>65 years old)

Safety and effectiveness in elderly patients above 65 have not been established.

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-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:

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, pnitrobenzene 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.