Ascorbic Acid

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release, Oral:

C-Time: 500 mg

Generic: 500 mg

Capsule Extended Release, Oral [preservative free]:

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 (118 mL, 473 mL)

Packet, Oral:

Generic: 500 mg (80 ea)

Powder, Oral:

Ascocid: (227 g)

Generic: (113 g, 120 g, 480 g)

Powder Effervescent, Oral:

Ascocid-ISO-pH: (150 g) [corn free, rye free, wheat free]

Solution, Injection:

Generic: 500 mg/mL (50 mL)

Solution, Injection [preservative free]:

Mega-C/A Plus: 500 mg/mL (50 mL [DSC])

Generic: 500 mg/mL (50 mL)

Solution, Intravenous [preservative free]:

Ascor: 500 mg/mL (50 mL) [contains edetate disodium]

Solution, Injection, as sodium ascorbate [preservative free]:

Ortho-CS 250: 250 mg/mL (100 mL [DSC]) [contains edetate disodium, water, sterile]

Generic: 250 mg/mL (30 mL [DSC])

Syrup, Oral:

Generic: 500 mg/5 mL (118 mL [DSC])

Tablet, Oral:

Asco-Tabs-1000: 1000 mg [color free, starch free, sugar free]

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

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]:

C-500: 500 mg [animal products free, gluten free, soy free, starch free, yeast free]

Generic: 500 mg

Tablet Extended Release, Oral:

Cemill: 500 mg

Cemill SR: 1000 mg

Generic: 500 mg, 1000 mg [DSC], 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)]

Pharmacology

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).

Pharmacokinetics/Pharmacodynamics

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)

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)

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

Onset of Action

Reversal of scurvy symptoms: 2 days to 3 weeks

Half-Life Elimination

10 hours (Schwedhelm 2003). Biological half-life: 8 to 40 days (IOM 2000)

Protein Binding

25%

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

Methemoglobinemiac

Data from multiple case reports suggest that IV ascorbic acid (vitamin C) may be effective for the treatment of methemoglobinemia, when methylene blue is contraindicated or unavailable Dhibar 2018, Faust 2018, Park 2017, Park 2014, Reeves 2016, Rehman 2018.

Severe sepsis or septic shockc

Data from one small, retrospective, before-after study suggest that IV ascorbic acid (vitamin C) in combination with IV hydrocortisone and IV thiamine in patients with severe sepsis or septic shock may be effective in decreasing mortality and preventing organ dysfunction Marik 2017. There are ongoing studies to confirm these findings in a larger population with a more robust study design.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

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): IV: 1.5 g over 30 to 60 minutes; repeat every 6 hours for 4 days or until ICU discharge; administer in combination with IV thiamine and IV hydrocortisone (Marik 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: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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:

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

Reconstitution

Prior to IV administration, dilute in a large volume parenteral solution (eg, D5W, SWFI). Refer to manufacturer's labeling for additional preparation instructions. Note: Pressure may develop in the vial during storage.

Administration

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.

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.

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

Storage

Injection: Store under refrigeration at 2°C to 8°C (36° to 46°F); protect from light. Use within 4 hours of vial entry; discard remaining portion.

Oral: Store at room temperature.

Drug Interactions

Aluminum Hydroxide: Ascorbic Acid may increase the absorption of Aluminum Hydroxide. Consider therapy modification

Amphetamines: Ascorbic Acid may decrease the serum concentration of Amphetamines. 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.). 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. Consider therapy modification

CycloSPORINE (Systemic): Ascorbic Acid may decrease the serum concentration of CycloSPORINE (Systemic). 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. Consider therapy modification

Estrogen Derivatives: Ascorbic Acid may increase the serum concentration of Estrogen Derivatives. Monitor therapy

Test Interactions

False-negative stool occult blood 48 to 72 hours after ascorbic acid ingestion.

May interfere with laboratory tests based on oxidation-reduction reactions (eg, blood and urine glucose testing, nitrite and bilirubin levels, leucocyte count). If possible, laboratory tests based on oxidation-reduction reactions should be delayed until 24 hours after dose.

Adverse Reactions

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

<1%: Diarrhea, dizziness, fatigue, flank pain, flushing, headache, heartburn, nausea, vomiting

Warnings/Precautions

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:

• Elderly: 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.

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 mcmol/L (0.2 to 0.4 mg/dL); Deficient: ≤11 mcmol/L (0.2 mg/dL)

Pregnancy

Pregnancy Risk Factor

C

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).

Patient Education

What is this drug used for?

• It is used to treat or prevent vitamin C deficiency.
• It is used to treat scurvy.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Diarrhea
• Nausea
• Vomiting
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Kidney stone like back pain, abdominal pain, or blood in the urine.
• Severe loss of strength and energy
• Dark urine
• Yellow skin
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.