Ascorbic acid (i.e., vitamin C, sodium ascorbate, ascorbate) is a water-soluble vitamin found in fruits and vegetables such as citrus fruits and green peppers. Ascorbic acid is a free radical, an antioxidant scavenger, and plays a major role in oxidation-reduction reactions. Ascorbic acid is a cofactor for enzymes involved in the biosynthesis of collagen (essential for tissue maintenance and repair), carnitine, and neurotransmitters. Humans cannot synthesize ascorbic acid endogenously and a lack of dietary intake can lead to scurvy. Intravenous ascorbic acid is FDA-approved for the treatment of scurvy. Vitamin C is also most frequently used as a nutritional supplement and as an adjunct in wound healing. It also is used as a treatment of methemoglobinemia as an alternative in patients who cannot receive methylene blue and with deferoxamine in the treatment of chronic iron toxicity. Vitamin C deficiency is highly prevalent during critical illness and high-dose vitamin C has been used in patients with sepsis, trauma, and burns with beneficial effects and no adverse effects. Ascorbic acid has also been used for a variety of ailments including the common cold, gum infections, acne, depression, fertility, and cancer; however, these claims have not been substantiated and vitamin C is not recommended for these purposes. Topical ascorbic acid is used as a protectant against free radicals, to brighten skin tone, and to lessen previous skin damage. It may also improve the look of facial wrinkles and fine lines.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-All dosage forms: Administer with a full glass of water. May be taken without regard to meals.
Oral Solid Formulations
-Chewable tablets: May be swallowed whole or chewed. Clinicians should note that chewable ascorbic acid may be damaging to tooth enamel.
-Extended-release tablets or capsules: Swallow whole without crushing, chewing, or breaking. Alternatively, the contents of the capsules may be mixed with a small amount of jelly or jam prior to administration.
Oral Liquid Formulations
-Oral solution: May be dropped directly into the mouth or mixed with fruit juice, cereal, or other food. Administer using a calibrated measuring device.
-Effervescent tablets: Dissolve in water immediately prior to administration.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Excess pressure may develop within the vial during storage; exercise caution when withdrawing contents from the vial and/or relieve pressure by first inserting sterile empty syringe into vial thus allowing pressure to equilibrate.
-When using dispensing vials, use aseptic technique. Dispense entire contents in aliquots under a laminar flow hood without delay or within 4 hours after entry or discard remaining content after first withdrawal. Prepare stoppers with a suitable antiseptic solution. Do not use unless solution is clear and seal is intact.
Intravenous Administration
Dilution
-Dilute in a compatible solution (i.e., 5% Dextrose Injection, 0.9% NaCl injection, Lactated Ringer's Injection) to a usual concentration of 1 to 25 mg/mL. Do NOT administer as an undiluted injection.
-Pharmacy Bulk Vial: Contents of vial must be used within 4 hours of initial entry. Discard unused portion.
-The dose should be immediately administered after admixture.
Intermittent IV infusion
-Administer as a slow IV infusion. Rapid IV administration of ascorbic acid should be avoided as temporary faintness, dizziness, flushing, lethargy, and headache may occur. Recommended administration rates are the following:-Adults: Administer no faster than 33 mg/minute (i.e., 200 mg given IV over 10 minutes).
-Children and Adolescents 11 to 17 years: Administer no faster than 33 mg/minute (i.e., 200 mg given IV over 10 minutes).
-Children 1 to 10 years: Administer no faster than 3.3 mg/minute (i.e., 100 mg given IV over 30 minutes).
-Infants 5 to 11 months: Administer no faster than 1.3 mg/minute (i.e., 50 mg given IV over 40 minutes).
Continuous IV infusion
-When used for the reduction of fluid resuscitation requirements in severely burned patients, ascorbic acid was diluted in Lactated Ringer's Injection to a 25 mg/mL concentration and administered at a rate of 66 mg/kg/hour.
Intramuscular Administration
-Inject deeply into a large muscle.
Subcutaneous Administration
-Inject subcutaneously taking care not to inject intradermally.
Topical Administration
Other Topical Formulations
Topical Serum
-Clean the area, then apply 5 to 7 drops of the serum.
-Wait for the serum to be absorbed into the skin.
-Apply moisturizer and SPF.
Oxalate, urate, or cystine renal stones (nephrolithiasis) causing renal tubular obstruction, characterized by costovertebral pain or lower back pain, can occur following large doses of ascorbic acid. Hyperoxaluria develops in 5% of patients taking large doses. Patients at an increased risk are those with renal disease, on hemodialysis, those with a history of nephrolithiasis, and children younger than 2 years.
Ascorbic acid is generally nontoxic. Diarrhea has resulted from oral dosages of more than 1 g daily; vomiting and abdominal cramps have also been reported. Rapid IV administration has resulted in temporary faintness or nausea, lethargy, flushing, dizziness, and headache. IV ascorbic acid should not be rapidly administered; follow administration rate guidelines.
Hemolytic anemia due to hemolysis has been observed in some patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency after receiving large IV or oral doses of ascorbic acid.
Excessive use of chewable ascorbic acid formulations can lead to dental caries or sensitivity from the breakdown of dental enamel.
Injection site reaction, such as pain and swelling, has been reported with intravenous administration of ascorbic acid.
There are no data available on ascorbic acid injection in human pregnancy to inform a drug-associated risk of adverse developmental outcomes; however, use of oral ascorbic acid has been used in pregnancy and no adverse developmental outcomes have been reported. In a meta-analysis of randomized studies of pregnant women who took oral vitamin C at doses ranging from 500 to 1,000 mg/day (2.5 to 5 times the recommended daily intravenous dose, respectively) between the ninth and 16th week of pregnancy, no increased risk of adverse pregnancy outcomes, such as miscarriage, preterm premature rupture of membranes, preterm delivery, or pregnancy-induced hypertension, were observed when compared to placebo. Follow the US Recommended Dietary Allowances (RDA) for pregnant women during treatment with ascorbic acid.
Ascorbic acid, vitamin C is distributed into breast milk. There are no data available on the effects of ascorbic acid on milk production or the breastfed infant. However, use of ascorbic acid within the recommended daily dietary intake for breast-feeding women is generally recognized as safe. In mothers not taking vitamin C supplements, vitamin C in human milk in the first 6 months of lactation varies from 34 to 83 mg/L. In mothers taking vitamin C supplements ranging from 45 to more than 1,000 mg/day, vitamin C content of human milk varies from 45 to 115 mg/L. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ascorbic acid and any potential adverse effects on the breast-fed infant from ascorbic acid or the underlying maternal condition. Follow the US Recommended Daily Allowances (RDA) for lactating women during treatment with ascorbic acid.
Acute and chronic oxalate nephropathy has been reported with prolonged administration of high doses of ascorbic acid. Acidification of the urine by ascorbic acid may lead to precipitation of cysteine, urate, or oxalate stones. Patients with renal disease, renal impairment, or renal failure, patients with a history of nephrolithiasis, and geriatric patients may be at increased risk. Infants and children less than 2 years may also be at increased risk due to immature kidney function. Monitor renal function during treatment with ascorbic acid in patients at increased risk. Discontinue ascorbic acid therapy in patients who develop oxalate nephropathy and treat as needed.
Large intravenous or oral doses of ascorbic acid have caused hemolysis and hemolytic anemia in some patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). Monitor hemoglobin and blood counts and use a reduced dose of ascorbic acid in patients with G6PD deficiency. Discontinue ascorbic acid treatment if hemolysis is suspected, and treat as required.
The sodium ascorbate preparation contains sodium. This can be of significance when treating patients on a sodium restriction diet, particularly if high doses of the sodium ascorbate preparation are given.
Ascorbic acid may increase the risk of iron toxicity in patients with hemochromatosis; therefore, patients with hemochromatosis should limit their intake of ascorbic acid to no more than 500 mg/day. Rarely, ingestion of large quantities of ascorbic acid have been associated with fatal cardiac arrhythmias in patients with iron overload.
Because ascorbic acid is a strong reducing agent, it can lead to laboratory test interference with laboratory tests based on oxidation-reduction reactions. Chemical detecting methods based on colorimetric reactions are generally those tests affected. Ascorbic acid can lead to inaccurate results obtained for checking blood or urinary glucose levels, nitrite, bilirubin, and leukocytes if tested during or within 24 hours after ascorbic acid infusion. If possible, laboratory tests based on oxidation-reduction reactions should be delayed until 24 hours after ascorbic acid infusion. Patients with diabetes mellitus should be made aware of the possibility of falsely elevated glucose concentrations with these tests. Additionally, ascorbic acid should not be ingested 48 to 72 hours before amine-dependent stool occult blood tests are conducted because false negatives may occur.
In the US, nutraceuticals are marketed under the Dietary Supplement and Health Education Act of 1994 (DSHEA). Consequently, scientific data supporting claimed benefit(s) are not always available for nutraceuticals as they are for traditional pharmaceuticals since nutraceuticals are not regulated as drugs. Consumers should also note that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products.
For the treatment of scurvy:
Oral dosage*:
Adults: 500 to 1,000 mg PO daily for 2 to 4 weeks or until body stores are replenished. Other dosage regimens include: 100 mg PO three times a day for 2 weeks, followed by 100 mg PO daily; or 1,000 to 2,000 mg PO daily for 2 to 3 days, followed by 500 mg PO daily for the next week, followed by 100 mg PO daily for 1 to 3 months.
Adolescents: 500 to 1,000 mg PO daily for 2 to 4 weeks or until body stores are replenished. Doses up to 1,500 mg PO daily have also been used in children.
Infants and Children: 100 to 300 mg PO daily for 2 to 4 weeks or until body stores are replenished. Doses up to 1,000 to 1,500 mg PO daily have also been used.
Intravenous dosage (Ascor):
Adults: 200 mg IV once daily for up to 1 week. If no improvement of symptoms is observed after 1 week of treatment, therapy may be repeated until resolution of symptoms is observed.
Children and Adolescents 11 to 17 years: 200 mg IV once daily for up to 1 week. If no improvement of symptoms is observed after 1 week of treatment, therapy may be repeated until resolution of symptoms is observed.
Children 1 to 10 years: 100 mg IV once daily for up to 1 week. Repeat dosing is not recommended.
Infants 5 to 11 months: 50 mg IV once daily for up to 1 week. Repeat dosing is not recommended.
Infants 1 to 4 months: Safety and efficacy have not been established.
Intravenous, Intramuscular, or Subcutaneous dosage (Generic products):
Adults: 300 to 1,000 mg IV, IM, or subcutaneously once daily is recommended; however, doses as high as 6,000 mg once daily have been used without evidence of toxicity. Although the product labeling recommends IM and subcutaneous for parenteral administration, the IV route is used in clinical practice.
For the treatment of methemoglobinemia*:
NOTE: Methylene blue is the first-line antidote treatment for severe methemoglobinemia; however, ascorbic acid may be used when methylene blue is contraindicated (i.e., glucose-6-dehydrogenase deficiency) or unavailable.
Intravenous dosage:
Adults: Doses ranging from 5 g IV every 6 hours for 6 doses up to 10 g IV every 6 hours (for approximately 2 days) have been used in patients with severe methemoglobinemia without adverse effects. Doses ranging from 500 mg IV once daily for 3 days, up to 1 g IV every 4 hours for 5 days, have been used in combination with IV methylene blue in case reports.
Infants, Children, and Adolescents: 1 to 2 g/day IV in 3 to 4 divided doses has been used in patients with severe methemoglobinemia.
Neonates: Data are very limited; however, single doses of 300 mg/kg IV have been used in case reports.
Oral dosage:
Adults: 1,000 mg PO once daily has been used in cases of mild/moderate methemoglobinemia.
Infants, Children, and Adolescents: 300 to 600 mg/day PO in divided doses, following IV treatment, has been used.
For the treatment of chronic iron toxicity* as an adjunct to deferoxamine therapy:
Oral dosage:
Adults: 200 mg PO once daily initiated after 1 month of regular deferoxamine treatment. It has also been recommended that vitamin C be administered 30 to 60 minutes before deferoxamine administration and only on days when receiving deferoxamine. Max: 2 to 3 mg/kg/day.
Children and Adolescents 10 to 17 years: 100 mg PO once daily initiated after 1 month of regular deferoxamine treatment. It has also been recommended that vitamin C be administered 30 to 60 minutes before deferoxamine administration and only on days when receiving deferoxamine. Max: 2 to 3 mg/kg/day.
Infants and Children 1 to 9 years: 50 to 100 mg PO once daily initiated after 1 month of regular deferoxamine treatment. It has also been recommended that vitamin C be administered 30 to 60 minutes before deferoxamine administration and only on days when receiving deferoxamine. Max: 2 to 3 mg/kg/day.
For urinary acidification*:
Oral dosage:
Adults: Doses ranging from 500 mg to 6 g/day PO have been most commonly used; however, efficacy of ascorbic acid for urinary acidification has been controversial.
For nutritional supplementation:
-the recommended dietary allowance (RDA) of ascorbic acid for nutritional supplementation in healthy individual:
NOTE: Recommendations updated by US Food and Nutrition Board, IOM, in 2000. Adequate intake (AI) may be higher.
Oral dosage:
Adult Males: 90 mg PO once per day. Alternatively, 100 mg PO once daily or twice daily has been recommended as the adequate intake to prevent deficiency.
Adult Females: 75 mg PO once per day. Alternatively, 100 mg PO once daily or twice daily has been recommended as the adequate intake to prevent deficiency.
Adult and Adolescent Pregnant Females: 80-85 mg PO once per day.
Adult and Adolescent Females during lactation: 115-120 mg PO once per day.
Adult Male Smokers: 125 mg PO once per day.
Adult Female Smokers: 110 mg PO once per day.
Adolescents 14-18 years: 65 mg PO once daily for females; 75 mg PO once daily for males.
Children 9-13 years: 45 mg PO once daily.
Children 4-8 years: 25 mg PO once daily.
Children 1-3 years: 15 mg PO once daily.
Infants: 40-50 mg PO once daily.
-to prevent vitamin C deficiency in patients receiving total parenteral nutrition (TPN):
Intravenous dosage:
Adults: 100 mg IV admixed in TPN each day.
For the treatment of chronic recurrent furunculosis* in patients with neutrophil dysfunction:
Oral dosage:
Adults: 1000 mg/day PO for 4-6 weeks was used in one study of 23 adults with multiple episodes of furunculosis each year. Twelve patients with neutrophil dysfunction responded dramatically; in 10 of these 12 patients, neutrophil function normalized for up to a year after treatment and they remained free of exacerbations. Ascorbic acid did not alter the course of furunculosis in patients without neutrophil dysfunction.
For reduction in resuscitation fluid volume requirements in patients with severe burns*:
Intravenous dosage:
Adults: Limited data suggest that 66 mg/kg/hour continuous IV for the first 24 hours after injury may be effective. Using the Parkland formula to estimate fluid needs, 37 patients with greater than 30% total body surface area burn were randomized to receive standard fluid resuscitation with Lactated Ringer's solution or continuous IV ascorbic acid as an additional component of the fluid resuscitation. The hourly Lactated Ringer's solution rate was adjusted to maintain desired hemodynamics and urine output in both groups. The initial 24-hour fluid resuscitation volume and second 24-hour fluid retention volume were significantly less in patients treated with ascorbic acid (5.5 +/- 3.1 mL/kg per percentage point of burn area for the control group vs 3 +/- 1.7 mL/kg per percentage point of burn area for the ascorbic acid group, p < 0.01). Water content volumes of the burned tissue were 6.1 +/- 1.8 mL/g of dry weight in the control group and 2.6 +/- 1.7 mL/g of dry weight in the ascorbic acid group (p < 0.01).
For adjunctive therapy in wound management (i.e., major trauma, burns, decubitus ulcer):
Intravenous dosage:
Adults: 1 g IV once daily for 5 days for major trauma and 14 to 21 days for major burns has been recommended. 3 g/day IV for 3 to 6 days has also been recommended. Product labeling recommendations are 300 to 500 mg IV once daily for 7 to 10 days and 1 to 2 g IV once daily for severe burns.
Oral dosage*:
Adults: 500 to 2,000 mg PO daily has been recommended.
Adolescents 14 to 17 years: 2,700 mg (1.5 times the upper intake level) PO in 3 divided doses for 7 days was used in a randomized, double-blind study in children (n = 32) with burns. Additionally, patients received supplementation with vitamin E and zinc. The time to complete tissue repair was significantly lower in the antioxidant supplemented group compared with placebo (p less than 0.001).
Children and Adolescents 9 to 13 years: 1,800 mg (1.5 times the upper intake level) PO in 3 divided doses for 7 days was used in a randomized, double-blind study in children (n = 32) with burns. Additionally, patients received supplementation with vitamin E and zinc. The time to complete tissue repair was significantly lower in the antioxidant supplemented group compared with placebo (p less than 0.001).
Children 4 to 8 years: 975 mg (1.5 times the upper intake level) PO in 3 divided doses for 7 days was used in a randomized, double-blind study in children (n = 32) with burns. Additionally, patients received supplementation with vitamin E and zinc. The time to complete tissue repair was significantly lower in the antioxidant supplemented group compared with placebo (p less than 0.001).
Children 1 to 3 years: 600 mg (1.5 times the upper intake level) PO in 3 divided doses for 7 days was used in a randomized, double-blind study in children (n = 32) with burns. Additionally, patients received supplementation with vitamin E and zinc. The time to complete tissue repair was significantly lower in the antioxidant supplemented group compared with placebo (p less than 0.001).
For adjunctive treatment and prevention of photoaging*, including palliation of fine facial wrinkles*:
Topical dosage:
Adults: Apply 5 to 7 drops of the serum in the morning after cleansing and toning. Follow labeled recommendations of specific product.
Maximum Dosage Limits:
-Adults
2 g/day PO is usual maximum dosage; however, doses up to 6 g/day PO have been used; 6 g/day IV is usual maximum dosage; however, doses up to 40 g/day IV have been used without evidence of toxicity.
-Geriatric
2 g/day PO is usual maximum dosage; however, doses up to 6 g/day PO have been used; 6 g/day IV is usual maximum dosage; however, doses up to 40 g/day IV have been used without evidence of toxicity.
-Adolescents
14 to 17 years: 1,500 mg/day PO is usual maximum dosage; however, doses up to 2,700 mg/day PO have been used; 200 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
13 years: 1,500 mg/day PO is usual maximum dosage; however, doses up to 1,800 mg/day PO have been used; 200 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
-Children
11 to 12 years: 1,500 mg/day PO is usual maximum dosage; however, doses up to 1,800 mg/day have been used; 200 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
9 to 10 years: 1,500 mg/day PO is usual maximum dosage; however, doses up to 1,800 mg/day have been used; 100 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
1 to 8 years: 1,500 mg/day PO; 100 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
-Infants
5 to 11 months: 300 mg/day PO; 50 mg/day IV is FDA-approved maximum dosage; however, doses up to 2 g/day IV have been used off-label.
1 to 4 months: 300 mg/day PO; safety and efficacy have not been established for IV formulation; however, doses up to 2 g/day IV have been used off-label.
-Neonates
Safety and efficacy have not been established; however, single doses up to 300 mg/kg IV have been used off-label for methemoglobinemia.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; however, ascorbic acid is primarily excreted in the kidneys, and dose reductions are recommended in patients with chronic renal failure. Additionally, patients with renal impairment may be at increased risk for developing acute or chronic oxalate nephropathy.
Intermittent hemodialysis
Specific guidelines for dosage adjustments in intermittent hemodialysis are not available; however, doses greater than 150 mg per day are not recommended.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Acetaminophen; Aspirin: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aluminum Hydroxide: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Carbonate: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Trisilicate: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Amphetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Amphetamine; Dextroamphetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Amphetamines: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Antacids: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aspirin, ASA: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Caffeine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aspirin, ASA; Dipyridamole: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Omeprazole: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Oxycodone: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Benzphetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Bismuth Subsalicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Bleomycin: (Moderate) Monitor for decreased efficacy of bleomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration of ascorbic acid and bleomycin may result in decreased efficacy of bleomycin.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Choline Salicylate; Magnesium Salicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Colesevelam: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
Deferoxamine: (Major) Patients should be advised not to take ascorbic acid, vitamin C supplements along with deferoxamine chelation therapy unless such supplements are prescribed with the approval of their health care professional. Patients with iron overload usually become vitamin C deficient, probably because iron oxidizes the vitamin. Vitamin C can be a beneficial adjunct in iron chelation therapy because it facilitates iron chelation and iron complex excretion. As an adjuvant to iron chelation therapy (e.g., deferoxamine), vitamin C (in doses up to 200 mg/day for adults, 50 mg/day in children < 10 years of age or 100 mg/day in older children) may be given in divided doses, starting after an initial month of regular treatment with deferoxamine. However, higher doses of ascorbic acid, vitamin C can facilitate iron deposition, particularly in the heart tissue, causing cardiac decompensation. In patients with severe chronic iron overload, the concomitant use of deferoxamine with > 500 mg/day PO of vitamin C in adults has lead to impairment of cardiac function; the dysfunction was reversible when vitamin C was discontinued. The manufacturer of deferoxamine recommends certain precautions for the coadministration of vitamin C with deferoxamine. First, vitamin C supplements should not be given concurrently with deferoxamine in patients with heart failure. Secondly, in other patients, such supplementation should not be started until 1 month of regular treatment with deferoxamine, and should be given only to patients receiving regular deferoxamine treatments. Do not exceed vitamin C doses of 200 mg/day for adults, 50 mg/day in children < 10 years of age, or 100 mg/day in older children, given in divided doses. Clinically monitor all patients, especially the elderly, for signs or symptoms of decreased cardiac function.
Desogestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Dextroamphetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Disulfiram: (Moderate) As ascorbic acid, vitamin C has on occasion been used as a specific antidote for symptoms resulting from interaction between ethanol and disulfiram, it may be expected that the administration of large doses of vitamin C may interfere with the effectiveness of disulfiram given to patients to encourage abstinence from alcohol.
Doxycycline: (Moderate) Monitor for decreased efficacy of doxycycline during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of doxycycline.
Drospirenone; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Erythromycin: (Moderate) Monitor for decreased efficacy of erythromycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of erythromycin.
Ethinyl Estradiol; Norelgestromin: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Ethinyl Estradiol; Norgestrel: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Etonogestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Fluphenazine: (Moderate) Monitor for decreased efficacy of fluphenazine during coadministration. Coadministration of ascorbic acid and fluphenazine may result in decreased plasma concentrations of fluphenazine due to acidification of the urine by ascorbic acid and increased excretion of fluphenazine.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Levonorgestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Lincomycin: (Moderate) Monitor for decreased efficacy of lincomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of lincomycin.
Lisdexamfetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Magnesium Hydroxide: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Magnesium Salicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Magnesium Salts: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Methamphetamine: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
Methenamine: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
Methenamine; Sodium Salicylate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
Mexiletine: (Minor) Ascorbic acid, vitamin C in doses greater than 2 grams per day can lower urinary pH, potentially causing enhanced the plasma clearance of mexiletine.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Norethindrone; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Norgestimate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Omeprazole; Sodium Bicarbonate: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Propranolol: (Minor) Ascorbic acid may reduce the oral bioavailability of propranolol. Advise patients against taking large doses of ascorbic acid with doses of propranolol.
Salsalate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects.
Sodium Bicarbonate: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Streptomycin: (Moderate) Monitor for decreased efficacy of streptomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of streptomycin.
Warfarin: (Minor) Monitor INR as per current standards of care when patients take vitamin C with warfarin. Limited case reports have suggested that high doses of ascorbic acid with warfarin may decrease the anticoagulation effects of warfarin. However, controlled studies have not confirmed an interaction. No effect was observed in patients on warfarin therapy treated with ascorbic acid doses up to 1,000 mg/day for 2 weeks.
Ascorbic acid is necessary for collagen formation (e.g., connective tissue, cartilage, tooth dentin, skin, and bone matrix) and tissue repair. It is reversibly oxidized to dehydroascorbic acid. Both forms are involved in oxidation-reduction reactions. Vitamin C is involved in the metabolism of tyrosine, carbohydrates, norepinephrine, histamine, and phenylalanine. Other processes that require ascorbic acid include biosynthesis of corticosteroids and aldosterone, proteins, neuropeptides, and carnitine; hydroxylation of serotonin; conversion of cholesterol to bile acids; maintenance of blood vessel integrity; and cellular respiration. Vitamin C may promote resistance to infection by the activation of leukocytes, production of interferon, and regulation of the inflammatory process. It reduces iron from the ferric to the ferrous state in the intestine to allow absorption, is involved in the transfer of iron from plasma transferrin to liver ferritin, and regulates iron distribution and storage by preventing the oxidation of tetrahydrofolate. Ascorbic acid enhances the chelating action of deferoxamine during treatment of chronic iron toxicity. Vitamin C may have a role in the regeneration of other biological antioxidants such as glutathione and alpha-tocopherol to their active state.
Ascorbate deficiency lowers the activity of microsomal drug-metabolizing enzymes and cytochrome P-450 electron transport. In the absence of vitamin C, impaired collagen formation occurs due to a deficiency in the hydroxylation of procollagen and collagen. Non-hydroxylated collagen is unstable, and the normal processes of tissue repair cannot occur. This results in the various features of scurvy including capillary fragility manifested as hemorrhagic processes, delayed wound healing, and bony abnormalities.
The use and dosage regimen of vitamin C in the prevention and treatment of diseases, other than scurvy, is unclear. Although further study is needed to recommend vitamin C therapy for the following ailments, data indicate a positive role for vitamin C for: overall decreased mortality, the prevention of coronary heart disease (especially in women), management of diabetes mellitus, reducing the risk of stroke, management of atherosclerosis in combination with other antioxidants, osteoporosis prevention, reducing the risk of Alzheimer disease in combination with vitamin E, and the prevention of cataracts.
Vitamin C is administered orally, topically, and by intramuscular, subcutaneous, or intravenous injection. The bioavailabilities of vitamin C from foods and supplements are similar; however, the bioavailability of vitamin C in foods is variable as it is easily degraded with cooking, processing, or the addition of preservatives (e.g., sodium bicarbonate). Approximately 70% to 90% of the usual dietary intake of ascorbic acid (30 to 180 mg/day) is absorbed, although absorption falls to 50% or less with doses above 1 g/day or in patients with GI disease (e.g., short bowel syndrome). Due to homeostatic regulation, the biological half-life of ascorbate varies widely from 8 to 40 days and is inversely related to body stores. Total body stores are approximately 1.5 g of ascorbic acid, with a daily turnover of 30 to 45 mg. Scurvy symptoms are associated with total body stores of less than 300 mg and 3 to 5 months of deficient vitamin C intake. High levels of ascorbate are maintained in the pituitary and adrenal glands, leukocytes, eye tissues and humors, and the brain. Vitamin C crosses the placenta and is distributed into breast milk.
Most ascorbic acid is reversibly oxidized to dehydroascorbic acid. The remainder is metabolized to the inactive metabolites (ascorbic acid-2-sulfate and oxalic acid) which are excreted in the urine. Of note, tobacco smoking increases oxidative stress and metabolic turnover of vitamin C, thereby increasing the suggested daily intake of vitamin C in smokers. Unmetabolized ascorbate is not excreted with normal dietary intake (80 mg/day or less); however, renal excretion increases proportionately with higher intake. When body stores become saturated, excess ascorbic acid is excreted unchanged in the urine; this is the basis for the ascorbic acid saturation test for vitamin C nutritional status. With large oral doses, unabsorbed ascorbate is degraded in the intestine, which may be the cause of diarrhea and intestinal discomfort.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
Vitamin C is absorbed orally through active transport.
Intravenous Route
Intravenous doses can produce plasma concentrations 30 to 70 fold higher than the maximum tolerated oral doses. Peak concentrations after IV administration are reached at the end of a 30 minute infusion. The elimination half-life of ascorbic acid after IV administration is approximately 7 hours.
-Special Populations
Renal Impairment
Ascorbic acid is removed by hemodialysis.