Vitamin C

A11A - Multivitamins, combinations ATC N/A

JFDA label: Ultimate DHEA 50 mg Capsule

Indications

Approved

Ascorbic acid deficiency
Dietary supplement
Scurvy

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Other (1)

Common Endocrine & metabolic: Hyperoxaluria (with large doses)

Dosing

Source: Lexicomp

Ascorbic acid deficiency: IM, IV, SubQ: 70 to 150 mg daily is an average protective dose; doses 3 to 5 times the RDA 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 Parenteral nutrition, maintenance requirement: IV: 200 mg/day (ASPEN [Vanek 2012]). 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). 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

(For additional information see "Vitamin C (ascorbic acid): Pediatric drug information") Parenteral nutrition, maintenance requirement: IV: Infants: 15 to 25 mg/kg/day; maximum daily dose: 80 mg/day (ASPEN [Vanek 2012]) Children and Adolescents: 80 mg daily (ASPEN [Vanek 2012]) Scurvy: Oral, IM, IV, SubQ: Initial: 100 mg/dose 3 times daily for 1 week (300 mg/day) followed by 100 mg once daily until normalization of tissue saturation, usually 1 to 3 months (AAP 2009; Weinstein 2001) IV: Ascor: Infants 5 months to Note: Retreatment is not recommended. Children ≥1 year to Note: Retreatment is not recommended. Children ≥11 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

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). 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 2008).

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.

Warnings & Precautions

Source: Lexicomp

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 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 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.

Pregnancy & Lactation

Pregnancy

FDA category C

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).

Lactation

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.

Monitoring

Clinical pearl	Renal function (patients at risk for developing oxalate nephropathy/nephrolithiasis); hemoglobin and blood counts (patients with G6PD deficiency).

Chemistry & Properties

Formula	C6H8O6
Molecular weight	176.12 g/mol
IUPAC name	(2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one
CAS	50-81-7
PubChem CID	54670067
InChIKey	`CIWBSHSKHKDKBQ-JLAZNSOCSA-N`
logP	-1.6 (XLogP -1.6)
Polar surface area	107.0 Å²
H-bond acceptors / donors	6 / 4

SMILES

C(C(C1C(=C(C(=O)O1)O)O)O)O

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (7)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Mamera Caplet	Tablet 1 mg, 30 mcg, 100 mg, 30 IU, 3000 IU, 200 IU, 3 mg, 3.4 mg, 20 mg, 20 mcg, 10 mg, 12 mcg, 200 mg, 25 mcg, 150 mcg, 25 mcg, 22.5 mg, 27 mg, 2 mg, 10 mg, 25 mg, 2.3 mg	30 tab	Jordan Sweden Medical & Sterilization Co.	2.420
Stresstab With Zinc	Tablet 0.5 mg, 25 ng, 600 mg, 45 IU, 30 mg, 10 mg, 100 mg, 10 mg, 25 mcg, 23.9 mg, 0.9 mg, 25 mg	30 tab	Sukhtian Group	2.930
Cal-C-Vita	Tablet 1 g, 300 IU, 15 mg, 250 mg	15 tab	The Jordan Drugstore Co	3.860
Pronatal	Tablet 0.6 mg, 2.6 mcg, 18 mg, 0.03 mg, 2 mg, 85 mg, 15 mg, 0.06 mg, 150 mg, 0.03 mg, 0.2 mg, 0.05 mg, 11 mg, 1.9 mg, 27 mg, 1 mg, 53 mg, 1.4 mg, 200 IU, 1.4 mg	30 tab	THE ARAB DRUG STORE P.S.C	5.570
Pharmaton Capsules	Capsule 20 mg, 15 mg, 10 mg, 60 mg, 400 IU, 2 mg, 4000 IU, 1 mcg, 90.3 mg, 1 mg, 10 mg, 1 mg, 10 mg, 40 mg, 10 mg, 1 mg, 2 mg, 8 mg, 66 mg, 1 mg, 26 mg, 70 mg, 0.2 mg	30 cap	THE ARAB DRUG STORE P.S.C	6.700
Elevit Pronatal film-coated tablets	Film-Coated Tablet 0.80 mg, 4.00 mcg, 19.00 mg, 10.00 mg, 200 mcg, 100.00 mg, 1080 mcg, 12.5 mcg, 125.00 mg, 7.50 mg, 2.60 mg, 60.00 mg, 1.00 mg, 125 mg, 1.00 mg, 1.80 mg, 100.00 mg, 1.60 mg, 15.00 mg	30 tab	The Jordan Drugstore Co	8.330
Ultimate DHEA	Capsule 25 mg, 70 mg, 90 mg, 50 mg	60 cap	Alghad Drug Store	25.000