Version May 2024
Ascorbic acid deficiency: IM, IV, SUBQ: 70 to 150 mg daily is an average protective dose; doses 3 to 5 times the recommended dietary allowance may be adequate for conditions with increased requirements.
Burns, nutritional supplement (off-label use): Oral: 500 mg twice daily; continue until burn wounds are healed or patient is discharged (Ref).
Methemoglobinemia (off-label use): Note: Consider when methylene blue is contraindicated (eg, suspected or documented G6PD deficiency) or unavailable; dose based on limited data, optimal dose has not been identified.
Usual dose range: IV: 1 to 10 g every 6 hours until methemoglobin levels normalize (Ref).
Nutritional supplement: Oral: 100 to 1,500 mg daily; dosage may vary depending on dosage form; consult specific product labeling.
Parenteral nutrition, maintenance requirement: IV: 200 mg/day (Ref).
Scurvy:
IM, IV, SUBQ: 300 to 1,000 mg daily; dose and duration of therapy should be individualized; doses up to 6 g per day have been administered (Ref).
Ascor: IV: 200 mg once daily for up to a maximum of 7 days. If no improvement after one week of treatment, retreat until resolution of symptoms is observed.
Oral: 100 to 300 mg daily until body stores are replenished; dose and duration of therapy should be individualized; doses as low as 10 mg may be effective (Ref).
Wound healing: IM, IV, SUBQ: 300 to 500 mg daily for 7 to 10 days pre- and post-operatively; larger doses have also been used.
Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling. Use with caution in patients with renal impairment or patients prone to recurrent renal calculi; may have increased risk of developing acute or chronic oxalate nephropathy.
ESRD (requiring hemodialysis):
Adults: IV, Oral: 60 to 100 mg once daily is sufficient to prevent serious ascorbate deficiency due to loss from dialysis; doses >100 mg daily may lead to secondary oxalosis and renal oxalate stone formation (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. Based on the pharmacokinetics of ascorbic acid, a water-soluble vitamin, a dosage adjustment does not seem necessary.
Refer to adult dosing.
(For additional information see "Vitamin C (ascorbic acid): Pediatric drug information")
Parenteral nutrition additive, maintenance requirement (Ref):
Infants: IV: 15 to 25 mg/kg/day; maximum daily dose: 80 mg/day.
Children and Adolescents: IV: 80 mg daily.
Scurvy, treatment:
Infants, Children, and Adolescents: Limited data available: Oral, IM, IV: Initial: 100 to 300 mg/day in divided doses for 1 week followed by 100 mg/day until normalization of tissue saturation (~1 to 3 months) (Ref).
Manufacturer's labeling: Ascor:
Infants ≥5 months: IV: 50 mg once daily for 1 week.
Children <11 years: IV: 100 mg once daily for 1 week.
Children ≥11 years and Adolescents: IV: 200 mg once daily for 1 week.
Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling. Use with caution in patients with renal impairment or patients prone to recurrent renal calculi; may have increased risk of developing acute or chronic oxalate nephropathy with high dose therapy.
ESRD (requiring hemodialysis): Children and Adolescents: IV, Oral: The KDOQI guidelines for nutrition in children recommend combined dietary and supplement intake should not greatly exceed the age-appropriate dietary reference intake; use caution in providing supplementation (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. Based on the pharmacokinetics of ascorbic acid, a water-soluble vitamin, a dosage adjustment does not seem necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Postmarketing:
Endocrine & metabolic: Hyperoxaluria (with large doses)
Hematologic & oncologic: Hemolysis (in patients with glucose-6-phosphate dehydrogenase deficiency)
Local: Pain at injection site, swelling at injection site
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Oxalate nephropathy/nephrolithiasis: Acidification of the urine by ascorbic acid may cause precipitation of cysteine, urate or oxalate stones. Acute and chronic oxalate nephropathy has been reported with prolonged administration of high IV doses. Patients with renal disease including renal impairment, history of oxalate kidney stones, elderly patients and pediatric patients <2 years of age may be at increased risk. Monitor renal function in patients at increased risk. Discontinue in patients who develop oxalate nephropathy.
Disease-related concerns:
• Diabetes: Patients with diabetes mellitus should not take excessive doses for extended periods of time.
• Glucose-6-phosphatase dehydrogenase deficiency: Hemolysis has been reported in patients with glucose-6-phosphatase dehydrogenase (G6PD) deficiency and the risk for severe hemolysis may be increased during ascorbic acid therapy. Dose reductions may be necessary along with appropriate monitoring (eg, hemoglobin, blood counts). Discontinue treatment if hemolysis is suspected.
• Hemochromatosis: Use with caution in patients with hemochromatosis; excess ascorbic acid intake may increase the risk of adverse events (IOM 2000).
• Renal impairment: Use with caution in patients with renal impairment or patients prone to recurrent renal calculi; may have increased risk of developing acute or chronic oxalate nephropathy.
Special populations:
• Older adult: Use with caution in the elderly; may be at increased risk for oxalate nephropathy.
• Pediatric: Use with caution in the children <2 years of age; may be at increased risk for oxalate nephropathy due to immature kidney function.
Dosage form specific issues:
• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register 2002). See manufacturer's labeling.
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Injection: Avoid rapid IV injection; may cause temporary faintness or dizziness.
• Sodium: Some products may contain sodium; use with caution in sodium restricted patients.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).
Following ascorbic acid administration, pediatric patients <2 years of age are at a higher risk for oxalate nephropathy due to age-related decreased glomerular filtration; monitor renal function during ascorbic acid treatment; discontinue ascorbic acid if oxalate nephropathy develops and provide treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release, Oral:
C-Time: 500 mg [DSC]
Generic: 500 mg
Crystals, Oral:
Vita-C: (120 g, 480 g) [animal products free, gelatin free, gluten free, lactose free, no artificial color(s), no artificial flavor(s), starch free, sugar free, yeast free]
Liquid, Oral:
BProtected Vitamin C: 500 mg/5 mL (236 mL) [contains propylene glycol, saccharin sodium, sodium benzoate; citrus flavor]
Generic: 500 mg/5 mL (120 mL, 473 mL)
Packet, Oral:
Generic: 500 mg (80 ea [DSC])
Powder, Oral:
Ascocid: (227 g [DSC])
Generic: (113 g, 120 g, 480 g)
Powder Effervescent, Oral:
Ascocid-ISO-pH: (150 g [DSC]) [corn free, rye free, wheat free]
Solution, Injection:
Generic: 500 mg/mL (50 mL [DSC])
Solution, Injection [preservative free]:
Generic: 500 mg/mL (50 mL)
Solution, Intravenous [preservative free]:
Ascor: 500 mg/mL (50 mL) [contains edetate (edta) disodium]
Tablet, Oral:
Asco-Tabs-1000: 1000 mg [DSC] [color free, starch free, sugar free]
True Vitamin C: 250 mg, 500 mg, 1000 mg
Generic: 100 mg, 250 mg, 500 mg, 1000 mg
Tablet, Oral [preservative free]:
Generic: 250 mg, 500 mg
Tablet Chewable, Oral:
Chew-C: 500 mg [DSC]
Fruit C 500: 500 mg [animal products free, gelatin free, gluten free, kosher certified, lactose free, no artificial color(s), no artificial flavor(s), starch free, sugar free, yeast free]
Fruit C: 100 mg [animal products free, gelatin free, gluten free, lactose free, no artificial color(s), no artificial flavor(s), starch free, sugar free, yeast free]
Fruity C: 250 mg
VitaChew Vit C Citrus Burst: 125 mg
Generic: 100 mg, 250 mg, 500 mg
Tablet Chewable, Oral [preservative free]:
Generic: 500 mg
Tablet Extended Release, Oral:
Generic: 500 mg, 1500 mg
Wafer, Oral [preservative free]:
Acerola C 500: 500 mg (50 ea) [corn free, no artificial color(s), no artificial flavor(s), wheat free, yeast free; contains acerola (malpighia glabra)]
May be product dependent
Chewable (Vitamin C Oral)
500 mg (per each): $0.05 - $0.07
Liquid (BProtected Vitamin C Oral)
500 mg/5 mL (per mL): $0.06
Solution (Ascor Intravenous)
25000 mg/50 mL (per mL): $6.42
Solution (Ascorbic Acid Injection)
500 mg/mL (per mL): $2.04
Tablets (Ascorbic Acid Oral)
500 mg (per each): $0.04 - $0.05
Wafer (Acerola C 500 Oral)
500 mg (per each): $0.07
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Ascor L 500: 500 mg/mL (50 mL) [contains edetate (edta) disodium]
Generic: 500 mg/mL (50 mL)
Solution, Injection, as sodium ascorbate:
Generic: 250 mg/mL (2 mL)
Oral administration is preferred unless malabsorption is suspected. IM administration is preferred when the parenteral route is required. Oral products may be administered with food.
Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Capsule may be opened and contents sprinkled onto soft food of choice. ER tablet should be switched to IR or chewable formulation.
Injection: For IM (preferred), IV, or SUBQ administration. Avoid rapid IV injection; may cause temporary faintness or dizziness.
Ascor: For IV use only. Following dilution in an appropriate IV solution (eg, D5W, SWFI), administer by slow IV infusion at a rate of 33 mg/minute.
Oral: Oral administration is preferred unless malabsorption is suspected. May be administered without regard to meals.
Parenteral:
Scurvy: IM, IV: Use only in circumstances when the oral route is not possible.
IM: Preferred parenteral route for some products due to improved utilization (refer to manufacturer labeling for appropriate products)
IV: Dose must be diluted prior to administration. Administer by slow IV infusion; rapid infusion (>250 mg/minute) may cause dizziness, nausea, lethargy, flushing, and headache.
Ascor: Doses should be infused at a rate not to exceed the following:
Infants 5 months to <12 months: 1.3 mg/minute
Children <11 years: 3.3 mg/minute
Children ≥11 years and Adolescents: 33 mg/minute
Ascorbic acid deficiency: Treatment of symptoms of mild deficiency; use in conditions requiring an increased intake (eg, wound healing).
Nutritional supplement: As a dietary vitamin C supplement.
Parenteral nutrition, maintenance requirement: Prevent and correct vitamin C deficiency as a supplement to IV total parenteral nutrition.
Scurvy: Prevention and treatment of scurvy.
Burns, nutritional supplement; Methemoglobinemia
Rubex [Ireland] may be confused with Brivex brand name for brivudine [Switzerland]
Rubex: Brand name for ascorbic acid [Ireland], but also the brand name for doxorubicin [Brazil]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aluminum Hydroxide: Ascorbic Acid may increase the absorption of Aluminum Hydroxide. Management: In patients with severe renal dysfunction, consider avoiding this combination. Administering agents at least 2 hours apart may help minimize effects. Monitor for toxic effects of aluminum (from antacid) if ascorbic acid is coadministered. Risk D: Consider therapy modification
Amphetamines: Gastrointestinal Acidifying Agents may decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
CycloSPORINE (Systemic): Ascorbic Acid may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Deferoxamine: Ascorbic Acid may enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern. Management: Limit the ascorbic acid dose to 200 mg/day (given in divided doses) in adult patients. In general, limit ascorbic acid to 50 mg daily for pediatric patients under 10 years old and 100 mg daily for older pediatric patients. Risk D: Consider therapy modification
Animal reproduction studies have not been conducted. Maternal plasma concentrations of ascorbic acid decrease as pregnancy progresses due to hemodilution and increased transfer to the fetus. Some pregnant women (eg, smokers) may require supplementation greater than the RDA (IOM 2000).
Ascorbic acid is present in breast milk; regulatory mechanisms prevent concentrations from exceeding a required amount (IOM 2000). According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Some products may contain sodium.
High dietary sources of ascorbic acid are citrus fruit, tomatoes/tomato juice, and potatoes; also found in other fruits, broccoli, cabbage, cauliflower, spinach, and strawberries. Absorption from diet and supplements is similar (IOM 2000).
Dietary recommended adequate intake (AI) (IOM 2000):
0 to 6 months: 40 mg daily
7 to 12 months: 50 mg daily
Dietary recommended daily allowance (RDA) (IOM 2000): Note: Patients with hemochromatosis, G6PD deficiency, and renal impairment may be at increased risk for adverse effects when exceeding recommended intake limits.
1 to 3 years: 15 mg daily; upper limit of intake should not exceed 400 mg daily
4 to 8 years: 25 mg daily; upper limit of intake should not exceed 650 mg daily
9 to 13 years: 45 mg daily; upper limit of intake should not exceed 1,200 mg daily
14 to 18 years: Upper limit of intake should not exceed 1,800 mg daily
Males: 75 mg daily
Females: 65 mg daily
Pregnant females: 80 mg daily; upper limit of intake should not exceed 1,800 mg daily
Lactating females: 115 mg daily; upper limit of intake should not exceed 1,800 mg daily
>18 years: Upper limit should not exceed 2,000 mg daily
Males: 90 mg daily
Females: 75 mg daily
Pregnant females: 19 to 50 years: 85 mg daily
Lactating females: 19 to 50 years: 120 mg daily
Adult smoker: Add an additional 35 mg daily
Renal function (patients at risk for developing oxalate nephropathy/nephrolithiasis); hemoglobin and blood counts (patients with G6PD deficiency).
Deficiency symptoms: May appear within 1 month of low intake (<10 mg/day) (ASPEN 2017; Vitamin C 2018). Symptoms include fatigue, malaise, corkscrew hair, and inflammation of the gums progressing to petechia, ecchymosis, purpura, joint pain, and poor wound healing.
Scurvy: Symptoms include depression; swollen, bleeding gums; loosening of teeth; and iron-deficiency anemia due to bleeding and decreased nonheme iron absorption (Vitamin C 2018).
Laboratory assessment: Plasma ascorbic acid is the preferred method of this vitamin's status (ASPEN 2017). Interpretation of plasma/ascorbic acid levels are as follows: Sufficient: >23 mcmol/L (0.4 mg/dL); Low: 12 to 23 mcmol/L (0.2 to 0.4 mg/dL); Deficient: ≤11 mcmol/L (0.2 mg/dL)
Ascorbic acid is an essential water soluble vitamin that acts as a cofactor and antioxidant. Ascorbic acid is an electron donor used for collagen hydroxylation, carnitine biosynthesis, and hormone/amino acid biosynthesis. It is required for connective tissue synthesis as well as iron absorption and storage (IOM 2000).
Onset of action: Reversal of scurvy symptoms: 2 days to 3 weeks
Absorption: Oral: Readily absorbed in the intestine; an active process thought to be saturable and dose dependent (30 to 180 mg/day: 70% to 90%; >1,000 mg/day: ≤50%) (IOM 2000)
Bioavailability: Oral: For doses up to 200 mg, nearly 100%; declines with increasing doses with ~33% for a single dose of 1250 mg (Schwedhelm 2003)
Distribution: Pituitary and adrenal glands, leukocytes, eye tissues and humors, and brain; lower concentrations in the plasma and saliva (IOM 2000)
Metabolism: Reversibly oxidized to dehydroascorbic acid (DHA); both ascorbic acid and DHA are active. Unabsorbed ascorbic acid is degraded in the intestine (IOM 2000)
Half-life elimination: 10 hours (Schwedhelm 2003). Biological half-life: 8 to 40 days (IOM 2000)
Excretion: Urine (with high serum concentrations) (IOM 2000); there is an individual specific renal threshold for ascorbic acid; when blood levels are high, ascorbic acid is excreted in urine, whereas when the levels are subthreshold (doses up to 80 mg/day) very little if any ascorbic acid is excreted into urine
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