Jucee 250 mg

1 INDICATIONS AND USAGE Ascorbic Acid Injection is indicated for the short term (up to 1 week) treatment of scurvy in adult and pediatric patients, age 5 months and older, for whom oral administration is not possible, insufficient or contraindicated. Limitations of Use Ascorbic Acid Injection is not indicated for the treatment of vitamin C deficiency that is not associated with signs and symptoms of scurvy. Ascorbic Acid Injection is vitamin C indicated for the short term (up to 1 week) treatment of scurvy in adult and pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated. Limitations of Use Ascorbic Acid Injection is not indicated for treatment of vitamin C deficiency that is not associated with signs and symptoms of scurvy.

2 DOSAGE AND ADMINISTRATION Supplied in a Pharmacy Bulk Package (PBP). Dispense single doses to multiple patients in a pharmacy admixture program; use within 4 hours of puncture. (2.1) Must be diluted prior to use (2.1) Administer as a slow intravenous infusion (2.1) See Full Prescribing Information for important administration instructions (2.1) Maximum recommended duration is one week (2.2) Population ​ (2.2) ​Recommended Doses Pediatric patients age 5 months to less than 12 months 50 mg once daily Pediatric patients age 1 year to less than 11 years 100 mg once daily Adults and pediatric patients age 11 years and older 200 mg once daily ​Specific Populations ​(2.3 , 8.1, 8.2 ) Pregnant women, lactating women, patients with glucose-6-phosphate dehydrogenase deficiency Should not exceed the U.S. Recommended Dietary Allowance (RDA) 2.1 Important Preparation and Administration Instructions Ascorbic Acid Injection vials contain 25,000 mg of ascorbic acid and the largest recommended single dose is 200 mg. Do not give the entire contents of the vial to a single patient. Do not administer Ascorbic Acid Injection as an undiluted intravenous injection. Minimize exposure to light because Ascorbic Acid Injection is light sensitive. Ascorbic Acid Injection is supplied as a Pharmacy Bulk Package (PBP) which is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion: a. Use only in a suitable ISO Class 5 work area such as a laminar flow hood (or an equivalent clean air compounding area). b. Penetrate each PBP vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Given that pressure may develop within the vial during storage, excercise caution when withdrawing contents from the vial. c. Once the closure system has been penetrated, complete all dispensing from the PBP vial within 4 hours . Each dose must be used immediately . Discard unused portion. d. Prior to administration, Ascorbic Acid Injection must be diluted in a suitable infusion solution and the final solution for infusion must be isotonic (undiluted the osmolarity of Ascorbic Acid Injection is approximately 5,900 mOsmol/L). Prior to preparing the admixture for infusion, calculate the osmolarity of the intended admixture for infusion. Add one daily dose of Ascorbic Acid Injection directly to an appropriate volume of a suitable infusion solution (e.g., 5% Dextrose Injection, Sterile Water for Injection) and add appropriate solutes, as necessary, to make the final solution isotonic. Sterile Water for Injection is highly hypotonic; adjust solute content, as necessary, to make the final infusion solution isotonic prior to injection. Do not mix Ascorbic Acid Injection with solutions containing elemental compounds that can be reduced (e.g., copper). The concentration of ascorbic acid in the final, admixture solution for infusion is to be in the range of 1 to 25 mg of ascorbic acid per mL. For example, for the largest recommended dose: Add 200 mg of ascorbic acid (equivalent to 0.4 mL of Ascorbic Acid Injection) to 7.5 mL of Sterile Water for Injection to produce an infusion solution having an approximate osmolarity of 290 mOsmol/L. In this specific example, addition of solute is NOT necessary because the solution is isotonic. e. Prepare the recommended dose based on the patient population [see Dosage and Administration (2.2), (2.3)]. f. Visually inspect for particulate matter and discoloration prior to administration (the diluted Ascorbic Acid Injection solution should appear colorless to pale yellow). g. Immediately administer the admixture for infusion as a slow intravenous infusion [see Recommended Dosage (2.2)]. 2.2 Recommended Dosage Table 1 provides recommended doses of Ascorbic Acid Injection based on patient population and infusion rates of diluted Ascorbic Acid Injection solution. Table 1: Recommended Dose of Ascorbic Acid Injection and Infusion Rate of Diluted Ascorbic Acid Injection Solution Patient Population Ascorbic Acid Injection Once Daily Dose (mg) Infusion Rate of Diluted Ascorbic Acid Injection Solution (mg/minute) Pediatric Patients age 5 months to less than 12 months 50 1.3 Pediatric Patients age 1 year to less than 11 years 100 3.3 Adults and Pediatric Patients 11 years and older 200 33 The recommended maximum duration of daily treatment with Ascorbic Acid Injection is seven days. If no improvement in scorbutic symptoms is observed after one week of treatment, retreat until resolution of scorbutic symptoms is observed. Repeat dosing is not recommended in pediatric patients less than 11 years of age. 2.3 Dosage Reductions in Specific Populations Women who are pregnant or lactating and patients with glucose-6-dehydrogenase deficiency should not exceed the U.S. Recommended Dietary Allowance (RDA) or daily Adequate Intake (AI) level for ascorbic acid for their age group and condition [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1, 8.2 )].

2.1 Important Preparation and Administration Instructions Ascorbic Acid Injection vials contain 25,000 mg of ascorbic acid and the largest recommended single dose is 200 mg. Do not give the entire contents of the vial to a single patient. Do not administer Ascorbic Acid Injection as an undiluted intravenous injection. Minimize exposure to light because Ascorbic Acid Injection is light sensitive. Ascorbic Acid Injection is supplied as a Pharmacy Bulk Package (PBP) which is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion: a. Use only in a suitable ISO Class 5 work area such as a laminar flow hood (or an equivalent clean air compounding area). b. Penetrate each PBP vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Given that pressure may develop within the vial during storage, excercise caution when withdrawing contents from the vial. c. Once the closure system has been penetrated, complete all dispensing from the PBP vial within 4 hours . Each dose must be used immediately . Discard unused portion. d. Prior to administration, Ascorbic Acid Injection must be diluted in a suitable infusion solution and the final solution for infusion must be isotonic (undiluted the osmolarity of Ascorbic Acid Injection is approximately 5,900 mOsmol/L). Prior to preparing the admixture for infusion, calculate the osmolarity of the intended admixture for infusion. Add one daily dose of Ascorbic Acid Injection directly to an appropriate volume of a suitable infusion solution (e.g., 5% Dextrose Injection, Sterile Water for Injection) and add appropriate solutes, as necessary, to make the final solution isotonic. Sterile Water for Injection is highly hypotonic; adjust solute content, as necessary, to make the final infusion solution isotonic prior to injection. Do not mix Ascorbic Acid Injection with solutions containing elemental compounds that can be reduced (e.g., copper). The concentration of ascorbic acid in the final, admixture solution for infusion is to be in the range of 1 to 25 mg of ascorbic acid per mL. For example, for the largest recommended dose: Add 200 mg of ascorbic acid (equivalent to 0.4 mL of Ascorbic Acid Injection) to 7.5 mL of Sterile Water for Injection to produce an infusion solution having an approximate osmolarity of 290 mOsmol/L. In this specific example, addition of solute is NOT necessary because the solution is isotonic. e. Prepare the recommended dose based on the patient population [see Dosage and Administration (2.2), (2.3)]. f. Visually inspect for particulate matter and discoloration prior to administration (the diluted Ascorbic Acid Injection solution should appear colorless to pale yellow). g. Immediately administer the admixture for infusion as a slow intravenous infusion [see Recommended Dosage (2.2)].

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.