Vitamin C (ascorbic acid): Drug information

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Pharmacologic Category
Vitamin, Water Soluble
Dosing: Adult
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: IM, IV, SubQ: 1 to 2 g daily for severe burns; dose may be determined by extent of tissue injury.
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 (Dhibar 2018; Faust
2018; Park 2014; Park 2017; Reeves 2016; Rehman 2018).
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 (American Society of Parenteral and Enteral
Nutrition 2019).
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 (per manufacturer).
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 (Hirschmann 1999; Popovich 2009; Weinstein
2001).
Severe sepsis or septic shock (off-label use): Note: Treatment of severe sepsis or septic shock with ascorbic
acid (vitamin C), with or without corticosteroids and thiamine, may be considered, but this therapy is
investigational and is not well defined at this time.
IV: 1.5 g over 30 to 60 minutes; repeat every 6 hours for 4 to 10 days until resolution of shock or until ICU
discharge; some clinicians administer in combination with IV thiamine and IV hydrocortisone (Fujii 2020;
Marik 2017; Moskowitz 2020; Nabil Habib 2017).
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.
Dosing: Renal Impairment: Adult
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 (ASPEN
[Mueller 2012]; Rolton 1991).
Dosing: Hepatic Impairment: Adult
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.
Dosing: Pediatric
(For additional information see "Vitamin C (ascorbic acid): Pediatric drug information")
Parenteral nutrition additive, maintenance requirement (ASPEN [Vanek 2012];
ESPGHAN/ESPEN/ESPR/CSPEN [Bronsky 2018]):
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)
(Kleinman 2013; Kliegman 2016; Popovich 2009; Weinstein 2001).

Manufacturer's labeling: Ascor:

Infant

Children <11 years: IV: 100 mg once daily for 1 week.

Dosing: Renal Impairment: Pediatric

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 (KDOQI 2009).
Dosing: Hepatic Impairment: Pediatric
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.

Dosing: Geriatric
Refer to adult dosing.

Administration: Adult
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.

Administration: Pediatric
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

Use: Labeled Indications

Ascorbic acid deficiency: Treatment of symptoms of mild deficiency; use in conditions requiring an increased
intake (eg, burns, 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
Use: Off-Label: Adult
Methemoglobinemia; Severe sepsis or septic shock
Medication Safety Issues
International issues:

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]

Adverse Reactions
1% to 10%: Endocrine & metabolic: Hyperoxaluria (with large doses)

<1%: Diarrhea, dizziness, fatigue, flank pain, flushing, headache, heartburn, nausea, vomiting
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Warnings/Precautions
Concerns related to adverse effects:

pathy/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:

-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.

increase the risk of adverse events (IOM 2000).

nal
calculi; may have increased risk of developing acute or chronic oxalate nephropathy.
Special populations:
 rs of age; may be at increased risk for oxalate nephropathy
due to immature kidney function.
Dosage form specific issues:

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.

(benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (

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.

Warnings: Additional Pediatric Considerations

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.
Metabolism/Transport Effects
None known.
Drug Interactions
(For additional information: Launch drug interactions program)

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: Ascorbic Acid may decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Bortezomib: Ascorbic Acid may diminish the therapeutic effect of Bortezomib. Management: Patients should avoid
taking vitamin C supplements and vitamin C-containing multivitamins during their bortezomib therapy. It is
probably unnecessary to advise patients to avoid foods/beverages that contain vitamin C (e.g., citrus fruits,
etc.). Risk D: Consider therapy modification
Copper: May decrease the serum concentration of Ascorbic Acid. Management: To minimize the risk for ascorbic
acid degradation, add multivitamin product to TPN solution immediately prior to infusion or administer
multivitamin and copper in separate containers. Risk D: Consider therapy modification
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: Avoid ascorbic acid doses greater than 200 mg/day. Lower doses may be
given to patients without cardiac failure, after one month of regular treatment with deferoxamine alone, ideally
soon after setting up the infusion pump. Monitor cardiac function. Risk D: Consider therapy modification
Estrogen Derivatives: Ascorbic Acid may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor
therapy
Pregnancy Risk Factor
C (show table)
Pregnancy Considerations
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).
Breast-Feeding Considerations
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.
Dietary Considerations
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

Monitoring Parameters
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

Mechanism of Action
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).
Pharmacodynamics and Pharmacokinetics
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 t

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