Ascor Drug Information

1. INDICATIONS AND USAGE ASCOR 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 ASCOR 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 Pharmacy Bulk Package (PBP). Dispense single doses to multiple patients in a pharmacy admixture program; use within 4 hours of puncture.

Must be diluted prior to use Administer as a slow intravenous infusion See Full Prescribing Information for important administration instructions Maximum recommended duration is one week Population ​ Supplied in Pharmacy Bulk Package (PBP). Must be diluted prior to use Administer as a slow intravenous infusion See Full Prescribing Information for important administration instructions Maximum recommended duration is one week Population ​ 2.1 Important Preparation and Administration Instructions ASCOR 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 ASCOR as an undiluted intravenous sensitive. Minimize exposure to light because ASCOR is light sensitive. ASCOR 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, ASCOR must be diluted in a suitable infusion solution and the final solution for infusion must be isotonic (undiluted the osmolarity of ASCOR 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 ASCOR 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 final solution isotonic.

Sterile Water for Injection is highly hypotonic; adjust solute content, as necessary, to make thet final infusion solution isotonic prior to injection. Do not mix ASCOR 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 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 ASCOR) 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. f.

Visually inspect for particulate matter and discoloration prior to administration (the diluted ASCOR solution should appear colorless to pale yellow). g. Discard unused portion. d. Immediately administer the admixture for infusion as a slow intravenous infusion 2.2 Recommended Dosage Table 1 provides recommended doses of ASCOR based on patient population and infusion rates of diluted ASCOR solution.

Table 1: Recommended Dose of ASCOR and Infusion Rate of Diluted ASCOR Solution The recommended maximum duration of daily treatment with ASCOR 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.

6. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Oxalate nephropathy and Nephrolithiasis Hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency 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.

ASCOR should not be rapidly administered. Acute and chronic oxalate nephropathy have occurred with prolonged administration of high doses of ascorbic acid. In patients with glucose-6-phosphate dehydrogenase deficiency severe hemolysis has occurred.

Most common adverse reactions are pain and swelling at the site of infusion ​To report SUSPECTED ADVERSE REACTIONS, contact McGuff Pharmaceuticals, Inc., toll free at 1-800-603-4795 or FDA at 1-800-FDA-1088 or ​www.fda.gov/medwatch.

7. DRUG INTERACTIONS ​Antibiotics:​ Ascorbic acid may decrease the activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin. Bleomycin is inactivated ​in vitro ​by ascorbic acid. ​Amphetamine and Other Drugs Affected by Urine Acidification:​ Ascorbic acid may cause acidification of the urine and result in decreased amphetamine serum levels affect excretion and plasma concentrations of other drugs sensitive to urine pH. ​Warfarin:​ Continue standard monitoring ​ See 17 for PATIENT COUNSELING INFORMATION ​Antibiotics: ​ Ascorbic acid may decrease the activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin.

If the antibiotic efficacy is suspected to be decreased by concomitant administration of ASCOR, discontinue ASCOR administration. 7.1 Antibiotics Ascorbic acid may decrease activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin. If the antibiotic efficacy is suspected to be decreased by concomitant administration of ASCOR, discontinue ASCOR administration. 7.2 Amphetamine & Other Drugs Affected by Urine Acidification 7.2 Amphetamine & Other Drugs Affected by Urine Acidification Ascorbic acid may acidify the urine and lower serum concentrations of amphetamine by increasing renal excretion (as reflected by changes in amphetamine urine recovery rates). In case of decreased amphetamine efficacy discontinue ASCOR administration.

Standard monitoring of therapy is warranted. In addition, acidification of urine by ascorbic acid will alter the excretion of certain drugs affected by the pH of the urine (e.g., fluphenazine) when administered concurrently. It has been reported that concurrent administration of ascorbic acid and fluphenazine has resulted in decreased fluphenazine plasma concentrations.

Standard monitoring of therapy is warranted. 7.2 Amphetamine & Other Drugs Affected by Urine Acidification Ascorbic acid may acidify the urine and lower serum concentrations of amphetamine by increasing renal excretion (as reflected by changes in amphetamine urine recovery rates). Standard monitoring of therapy is warranted. 7.3 Warfarin 7.3 Warfarin Limited case reports have suggested interference of ascorbic acid with the anticoagulation effects of warfarin, however, patients on warfarin therapy treated with ascorbic acid doses up to 1000 mg/day (5 times the largest recommended single dose) for 2 weeks (twice the maximum recommended duration), no effect was observed. Standard monitoring for anti-coagulation therapy should continue during ascorbic acid treatment, as per standard of care. 7.4 Laboratory Test Interference 7.4 Laboratory Test Interference Because ascorbic acid is a strong reducing agent, it can interfere with numerous laboratory tests based on oxidation-reduction reactions (e.g., glucose, nitrite and bilirubin levels, leukocyte count, etc.).

Chemical detecting methods based on colorimetric reactions are generally those tests affected. Ascorbic acid may lead to inaccurate results (false negatives) obtained for checking blood or urinary glucose levels, nitrite, bilirubin, and leukocytes if tested during or within 24 hours after infusion. 7.4 Laboratory Test Interference Because ascorbic acid is a strong reducing agent, it can interfere with numerous laboratory tests based on oxidation-reduction reactions (e.g., glucose, nitrite and bilirubin levels, leukocyte count, etc.).

4. CONTRAINDICATIONS None. None.

10. OVERDOSAGE Overdose with ascorbic acid may cause nausea, vomiting, diarrhea, facial flushing, rash, headache, fatigue or disturbed sleep. If overdose of ASCOR occurs, immediately discontinue administration and treat symptoms and signs of overdose, avoiding additional intake of ascorbic acid.