Ascorbic Acid

5 WARNINGS AND PRECAUTIONS Oxalate nephropathy and Nephrolithiasis: Ascorbic acid has been associated with development of acute or chronic oxalate nephropathy following prolonged use of high doses of ascorbic acid infusion. Patients with renal disease including renal impairment, history of oxalate kidney stones, geriatric patients, and pediatric patients less than 2 years old may be at increased risk ( 5.1 ). Hemolysis : Patients with glucose-6-phosphate dehydrogenase deficiency are at risk of severe hemolysis; a reduced dose is recommended ( 5.2 ). Laboratory Test Interference: Ascorbic acid may interfere with laboratory tests based on oxidation-reduction reactions, including blood and urine glucose testing ( 5.3 ). 5.1 Oxalate Nephropathy and Nephrolithiasis Acute and chronic oxalate nephropathy have been reported with prolonged administration of high doses of ascorbic acid. Acidification of the urine by ascorbic acid may cause precipitation of cysteine, urate or oxalate stones. Patients with renal disease including renal impairment, history of oxalate kidney stones, and geriatric patients may be at increased risk for oxalate nephropathy while receiving treatment with ascorbic acid. Pediatric patients less than 2 years of age may be at increased risk for oxalate nephropathy during treatment with ascorbic acid because their kidneys are immature [see Use in Specific Populations ( 8.4, 8.5, 8.6 )]. Monitor renal function in patients at increased risk receiving Ascorbic Acid Injection. Discontinue Ascorbic Acid Injection in patients who develop oxalate nephropathy and treat any suspected oxalate nephropathy. Ascorbic Acid Injection is not indicated for prolonged administration (the maximum recommended duration is one week) [see Dosage and Administration ( 2.1 )] . 5.2 Hemolysis in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Hemolysis has been reported with administration of ascorbic acid in patients with glucose-6-phosphate dehydrogenase deficiency. Patients with glucose-6-phosphate dehydrogenase deficiency may be at increased risk for severe hemolysis during treatment with ascorbic acid. Monitor hemoglobin and blood count and use a reduced dose of Ascorbic Acid Injection in patients with glucose-6-phosphate dehydrogenase deficiency [see Dosage and Administration (2.3) ]. Discontinue treatment with Ascorbic Acid Injection if hemolysis is suspected and treat as needed. 5.3 Laboratory Test Interference Ascorbic acid may interfere with laboratory tests based on oxidation-reduction reactions, including blood and urine glucose testing, nitrite and bilirubin levels, and leucocyte count testing. If possible, laboratory tests based on oxidation-reduction reactions should be delayed until 24 hours after infusion of Ascorbic Acid Injection [see Drug Interactions ( 7.4 )].

5.1 Oxalate Nephropathy and Nephrolithiasis Acute and chronic oxalate nephropathy have been reported with prolonged administration of high doses of ascorbic acid. Acidification of the urine by ascorbic acid may cause precipitation of cysteine, urate or oxalate stones. Patients with renal disease including renal impairment, history of oxalate kidney stones, and geriatric patients may be at increased risk for oxalate nephropathy while receiving treatment with ascorbic acid. Pediatric patients less than 2 years of age may be at increased risk for oxalate nephropathy during treatment with ascorbic acid because their kidneys are immature [see Use in Specific Populations ( 8.4, 8.5, 8.6 )]. Monitor renal function in patients at increased risk receiving Ascorbic Acid Injection. Discontinue Ascorbic Acid Injection in patients who develop oxalate nephropathy and treat any suspected oxalate nephropathy. Ascorbic Acid Injection is not indicated for prolonged administration (the maximum recommended duration is one week) [see Dosage and Administration ( 2.1 )] .

5.2 Hemolysis in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Hemolysis has been reported with administration of ascorbic acid in patients with glucose-6-phosphate dehydrogenase deficiency. Patients with glucose-6-phosphate dehydrogenase deficiency may be at increased risk for severe hemolysis during treatment with ascorbic acid. Monitor hemoglobin and blood count and use a reduced dose of Ascorbic Acid Injection in patients with glucose-6-phosphate dehydrogenase deficiency [see Dosage and Administration (2.3) ]. Discontinue treatment with Ascorbic Acid Injection if hemolysis is suspected and treat as needed.

5.3 Laboratory Test Interference Ascorbic acid may interfere with laboratory tests based on oxidation-reduction reactions, including blood and urine glucose testing, nitrite and bilirubin levels, and leucocyte count testing. If possible, laboratory tests based on oxidation-reduction reactions should be delayed until 24 hours after infusion of Ascorbic Acid Injection [see Drug Interactions ( 7.4 )].

6. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Oxalate nephropathy and Nephrolithiasis [see Warnings and Precautions ( 5.1 )]. Hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency [see Warnings and Precautions ( 5.2 )]. The following adverse reactions associated with the use of ascorbic acid were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure: Administration site reactions : pain and swelling. Ascorbic Acid Injection should not be rapidly administered. Rapid intravenous administration (>250 mg/minute) of Ascorbic Acid Injection may cause temporary faintness or nausea, lethargy, flushing, dizziness, and headache (the recommended infusion rates of diluted Ascorbic Acid Injection solution are 1.3 mg/minute (Pediatric Patients age 5 months to less than 12 months), 3.3 mg/minute (Pediatric Patients age 1 year to less than 11 years) and 33 mg/minute (Adults and Pediatric Patients 11 years and older) [see Dosage and Administration ( 2.2 )]) . Acute and chronic oxalate nephropathy have occurred with prolonged administration of high doses of ascorbic acid [see Warnings and Precautions ( 5.1 )]. In patients with glucose-6-phosphate dehydrogenase deficiency, severe hemolysis has occurred [see Warnings and Precautions ( 5.2 )]. Most common adverse reactions are pain and swelling at the site of infusion (6) To report SUSPECTED ADVERSE REACTIONS, contact Renova Pharmaceuticals LLC. at 1-888-211-5593 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.