Aquasol A

Fish Oil Supplements
Vitamin A Supplements (new)

Administer vitamin A orally with or after meals.

For ease of administration, vitamin A liquid doses have been squeezed from gelatinous capsules (soft gel capsules) for administration directly into the patient's mouth, or alternatively mixed with formula, breast-milk or soft foods. If mixed, ensure consumption of the intended dose.

Measure dose using a calibrated oral dropper, syringe or other oral measuring device to ensure accurate dosing.
May administer directly into the mouth or mix with fruit juice, cereal, or other food. Infants may receive the drops in formula or human milk.
Stability: Follow specific manufacturer instructions; most products should be discarded within 6—8 weeks after opening due to loss of potency.

Protect from light. Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Parenteral therapy is only indicated when oral therapy is not feasible (i.e., NPO status, malabsorption, vomiting, or when ocular damage is severe).
For intramuscular (IM) administration only. Do NOT administer vitamin A injection intravenously due to the risk of anaphylactic shock and possibly death.

Inject deeply into a large muscle.

teratogenesis / Delayed / Incidence not known
increased intracranial pressure / Early / Incidence not known
hepatotoxicity / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
hypervitaminosis A / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
renal failure / Delayed / Incidence not known

exophthalmos / Delayed / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
hepatomegaly / Delayed / Incidence not known
ascites / Delayed / Incidence not known
decreased HDL cholesterol (HDL-C) concentration / Delayed / Incidence not known

anorexia / Delayed / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
irritability / Delayed / Incidence not known
lethargy / Early / Incidence not known
arthralgia / Delayed / Incidence not known
headache / Early / Incidence not known
xerosis / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
nausea / Early / Incidence not known
malaise / Early / Incidence not known
dysmenorrhea / Delayed / Incidence not known
vomiting / Early / Incidence not known
alopecia / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known

A Mulsin, A-Caro-25, Aquasol A, Dofsol-A

Rx, OTC

Fat-soluble vitamin
Used orally or intramuscularly to prevent and treat vitamin A deficiency
Important for proper immune function, vision, reproduction, and growth and development

3,000 mcg RAE (10,000 International Units) PO once daily or 7,500 mcg RAE (25,000 International Units) PO once weekly for a minimum of 12 weeks during pregnancy until delivery. Vitamin A supplementation is not recommended during pregnancy as part of routine antenatal care for the prevention of maternal and infant morbidity and mortality. These periodic, high dose vitamin A regimens are used primarily outside the United States and other developed countries where access to adequate dietary intake of vitamin A is lacking and where the prevalence of night blindness is 5% or higher in pregnant persons or children 24 to 59 months.

60,000 mcg RAE (200,000 International Units) PO every 4 to 6 months. These periodic, high dose vitamin A regimens are used primarily outside the United States and other developed countries where access to adequate dietary intake of vitamin A is lacking and where the prevalence of night blindness is 1% or higher in children 24 to 59 months or where the prevalence of vitamin A deficiency is 20% or higher in infants and children 6 to 59 months.

30,000 mcg RAE (100,000 International Units) PO as a single dose. These periodic, high dose vitamin A regimens are used primarily outside the United States and other developed countries where access to adequate dietary intake of vitamin A is lacking and where the prevalence of night blindness is 1% or higher in children 24 to 59 months or where the prevalence of vitamin A deficiency is 20% or higher in infants and children 6 to 59 months.

900 mcg RAE/day (3,000 International Units/day) PO is the RDA.

700 mcg RAE/day (2,300 International Units/day) PO is the RDA.

770 mcg RAE/day (2,565 International Units/day) PO is the RDA.

1,300 mcg RAE/day (4,300 International Units/day) PO is the RDA.

900 mcg RAE/day (3,000 International Units/day) PO is the RDA.

700 mcg RAE/day (2,300 International Units/day) PO is the RDA.

750 mcg RAE/day (2,500 International Units/day) PO is the RDA.

1,200 RAE/day (4,000 International Units/day) PO is the RDA.

600 mcg RAE/day (2,000 International Units/day) PO is the RDA.

400 mcg RAE/day (1,300 International Units/day) PO is the RDA.

300 mcg RAE/day (1,000 International Units/day) PO is the RDA.

500 mcg RAE/day (1,650 International Units/day) PO is the recommended Adequate Intake based on dietary intake of breast milk, formula, or other food sources. No RDA has been established.

400 mcg RAE/day (1,300 International Units/day) PO is the recommended Adequate Intake, based on dietary intake of human breast milk. No RDA has been established.

400 mcg RAE/day (1,300 International Units/day) PO is the recommended Adequate Intake, based on dietary intake of human breast milk. No RDA has been established.

210 to 450 mcg/kg/day RAE (700 to 1,500 International Units/kg/day) PO. Supplementation of premature infants with 450 mcg/kg/day RAE (1,500 International Units/kg/day) PO results in normalization of serum retinol and RBP concentrations. Most specialized feeding formulas for premature infants provide this amount of vitamin A; however, neonates receiving breast milk will require supplementation to provide adequate nutritional intake.

3,000 mcg RAE (10,000 International Units) PO once daily.

3,000 mcg RAE (10,000 International Units) PO once daily.

1,500 to 3,000 mcg RAE (5,000 to 10,000 International Units) PO once daily.

1,500 mcg RAE (5,000 International Units) PO once daily.

450 mcg RAE (1,500 International Units) PO once daily.

450 mcg RAE (1,500 International Units) PO once daily.

30,000 mcg RAE (100,000 International Units) IM once daily for 3 days, then 15,000 mcg RAE (50,000 International Units) IM once daily for 14 days. Follow with an oral supplement.

30,000 mcg RAE (100,000 International Units) IM once daily for 3 days, then 15,000 mcg RAE (50,000 International Units) IM once daily for 14 days. Follow with an oral supplement.

5,300 to 10,600 mcg RAE (17,500 to 35,000 International Units) IM once daily for 10 days. Follow with an oral supplement.

2,250 to 4,500 mcg RAE (7,500 to 15,000 International Units) IM once daily for 10 days. Follow with an oral supplement.

2,250 to 4,500 mcg RAE (7,500 to 15,000 International Units) IM once daily for 10 days. Follow with an oral supplement.

Dosage regimen has not been established. Most regimens begin soon after birth, usually by day 4, and continue up to 28 days. Dosage regimens studied for chronic lung disease prevention have included: 1,200 to 1,500 mcg RAE (4,000 to 5,000 International Units) IM 3 times weekly; 600 to 1,200 mcg RAE (2,000 to 4,000 International Units) IM every other day; and 450 to 900 mcg RAE (1,500 to 3,000 International Units) IM on days 1, 3, and 7.[53923] High dose regimens (3,000 mcg RAE [10,000 International Units] IM 3 times weekly for 4 weeks and 4,500 mcg RAE [15,000 International Units] IM weekly for 4 weeks) have also been studied, but have shown no additional benefit.[54031] In a Cochrane analysis of vitamin A supplementation in very low birth weight infants, vitamin A supplementation was found to have a modest benefit in reducing death and oxygen requirements at 1 month of age vs. placebo, regardless of dosing regimen used (RR 0.93; 95% CI, 0.88 to 0.99).[53923]

3,000 to 6,000 mcg RAE (10,000 to 20,000 International Units) PO once daily for 2 months after initial IM dosing for 17 days.

3,000 to 6,000 mcg RAE (10,000 to 20,000 International Units) PO once daily for 2 months after initial IM dosing for 17 days.

1,500 to 3,000 mcg RAE (5,000 to 10,000 International Units) PO once daily for 2 months after initial IM dosing for 10 days.

1,500 to 3,000 mcg RAE (5,000 to 10,000 International Units) PO once daily for 2 months after initial IM dosing for 10 days.

210 to 450 mcg/kg/day RAE (700 to 1,500 International Units/kg/day) PO is recommended by the American Academy of Pediatrics (AAP). Supplementation of premature infants with 450 mcg/kg/day (1,500 International Units/kg/day) results in normalization of serum retinol and RBP concentrations. Most specialized feeding formulas for premature infants provide this amount of vitamin A; however, breast milk will require supplementation to provide adequate amounts of vitamin A.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A. If the woman is pregnant, it is necessary to balance the risk of possible teratogenic effects to the fetus with the serious consequences of vitamin A deficiency.

1,500 to 3,000 mcg RAE (5,000 to 10,000 International Units) PO once daily or 7,500 mcg RAE (25,000 International Units) PO once weekly for at least 4 weeks. Max: 3,000 mcg/day RAE (10,000 International Units/day) PO, unless administering the weekly regimen.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A. If the woman is pregnant, it is necessary to balance the risk of possible teratogenic effects to the fetus with the serious consequences of vitamin A deficiency.

1,500 to 3,000 mcg RAE (5,000 to 10,000 International Units) PO once daily or 7,500 mcg RAE (25,000 International Units) PO once weekly for at least 4 weeks. Max: 3,000 mcg/day RAE (10,000 International Units/day) PO, unless administering the weekly regimen.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

30,000 mcg RAE (100,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

15,000 mcg RAE (50,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

15,000 mcg RAE (50,000 International Units) PO once daily for 2 days, followed by another dose at least 2 weeks later for a total of 3 doses. Treatment should begin immediately upon diagnosis; corneal lesions are indicative of a medical emergency and require urgent treatment after the first dose of vitamin A.

60,000 mcg RAE (200,000 International Units) PO once daily for 2 days, followed by an additional dose 4 to 6 weeks later if the child has clinical signs of vitamin A deficiency, such as Bitot's spots. High-dose vitamin A supplementation has been shown to decrease morbidity and mortality due to severe measles in patients with and without underlying vitamin A deficiency. In a Cochrane analysis, a greater reduction in the risk of mortality was observed in children younger than 2 years.

30,000 mcg RAE (100,000 International Units) PO once daily for 2 days, followed by an additional dose 4 to 6 weeks later if the child has clinical signs of vitamin A deficiency, such as Bitot's spots. High-dose vitamin A supplementation has been shown to decrease morbidity and mortality due to severe measles in patients with and without underlying vitamin A deficiency. In a Cochrane analysis, a greater reduction in the risk of mortality was observed in children younger than 2 years.

15,000 mcg RAE (50,000 International Units) PO once daily for 2 days, followed by an additional dose 4 to 6 weeks later if the child has clinical signs of vitamin A deficiency, such as Bitot's spots. High-dose vitamin A supplementation has been shown to decrease morbidity and mortality due to severe measles in patients with and without underlying vitamin A deficiency. In a Cochrane analysis, a greater reduction in the risk of mortality was observed in children younger than 2 years.

15,000 mcg RAE (50,000 International Units) PO once daily for 2 days, followed by an additional dose 4 to 6 weeks later if the child has clinical signs of vitamin A deficiency, such as Bitot's spots. High-dose vitamin A supplementation has been shown to decrease morbidity and mortality due to severe measles in patients with and without underlying vitamin A deficiency. In a Cochrane analysis, a greater reduction in the risk of mortality was observed in children younger than 2 years.

Vitamin A 4,500 mcg/day RAE (15,000 International Units/day) PO was found superior to vitamin E or placebo in 601 patients with retinitis pigmentosa. Vitamin A was administered daily as retinyl palmitate and patients were studied for 4 years after randomization.

1,500 to 15,000 mcg/day RAE (50,000 to 500,000 International Units/day) PO has been used for several weeks historically; however, high doses and toxicity limit usefulness. Retinoids such as acitretin and isotretinoin are more commonly used.

Dosage regimen has not been established. Most regimens begin soon after birth, usually by day 4, and continue up to 28 days. Dosage regimens have included: 1,200 to 1,500 mcg RAE (4,000 to 5,000 International Units) IM 3 times per week; 600 to 1,200 mcg RAE (2,000 to 4,000 International Units) IM every other day; 450 to 900 mcg RAE (1,500 to 3,000 International Units) IM on days 1, 3, and 7.[53923] In a Cochrane analysis of vitamin A supplementation in very low birth weight infants (less than 32 weeks gestation; birth weight 1.5 kg or less), vitamin A supplementation was found to have a modest benefit in reducing death and oxygen requirements at 1 month of age versus placebo, regardless of dosing regimen used (RR 0.93, 95% CI 0.88 to 0.99, number needed to treat to benefit = 20).[53923]

More study is needed to determine optimal testing parameters. 2,400 mcg RAE (8,000 International Units) PO of oil-soluble vitamin A as a single dose has been used. Serum retinyl ester concentrations were measured before (fasting) and at various time points from 3 and 7 hours after administration in order to measure peak concentrations. The usual test for fat malabsorption is fecal fat testing.

Initial doses of 180 to 300 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

Initial doses of 180 to 300 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

Initial doses of 150 to 180 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

Initial doses of 120 to 150 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

Initial doses of 15 to 120 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

Initial doses of 15 to 90 mg/day PO have been recommended. Doses should be adjusted as necessary to maintain a serum beta-carotene concentration of at least 800 mcg/dL for 3 months. Discontinue treatment after 3 months if no significant improvement in symptoms.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available. Patients with underlying hepatic disease may be at increased risk for the development of hypervitaminosis A and close monitoring may be needed in patients receiving supplementation over the usual recommended dietary intakes.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Calcium: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
Castor Oil: (Moderate) Absorption of fat-soluble vitamins may be decreased with coadministration of castor oil.
Cholestyramine: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
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.
Colestipol: (Moderate) Separate administration of fat-soluble vitamins by 1 hour before or 4 hours after a colestipol dose to limit effects on oral absorption. Because it sequesters bile acids, colestipol may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins.
Methoxsalen: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Mineral Oil: (Moderate) Absorption of fat-soluble vitamins is reported to be decreased with prolonged oral administration of mineral oil. However, despite warnings in various texts, there is little direct evidence that the interaction is of practical/clinical importance with limited use as directed. It may be prudent for those taking dietary supplements of Vitamin A, D, E, or K to separate administration by 1 hour before or 4 hours after a mineral oil oral dosage to help limit absorption interactions. Theoretically, the effect on fat-soluble vitamin absorption may more likely occur with prolonged or chronic administration of mineral oil.
Orlistat: (Moderate) Due to orlistat's mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. The manufacturer recommends that fat-soluble vitamin supplements be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
Palovarotene: (Major) Avoid concomitant use of palovarotene and vitamin A supplements due to the risk for hypervitaminosis A.
Porfimer: (Major) Avoid coadministration of porfimer with retinoids due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Risedronate: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
St. John's Wort, Hypericum perforatum: (Moderate) In theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's wort with other photosensitizing drugs such as retinoids.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with retinoids is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.

Aquasol A Intramuscular Inj Sol: 1mL, 50000U
Dofsol-A/Vitamin A Oral Cap: 50000IU

The following are recommended Tolerable Upper Intake Levels (UL) in healthy, non-vitamin deficient individuals. The UL is defined as the highest daily intake of a nutrient that is likely to pose no risk in otherwise healthy individuals. The ULs are not intended to apply to individuals with specific disease states. The ULs for vitamin A apply to both food and supplement intake where vitamin A is from animal sources. These limits were set based upon risk of liver toxicity in adults, teratogenic effects, and toxic effects in infants and children.

19 years and older: 3,000 mcg/day RAE (10,000 International Units/day) PO.
18 years: 2,800 mcg/day RAE (9,333 International Units/day) PO.

3,000 mcg/day RAE (10,000 International Units/day) PO.

14 to 17 years: 2,800 mcg/day RAE (9,333 International Units/day) PO.
13 years: 1,700 mcg/day RAE (5,667 International Units/day) PO.

9 to 12 years: 1,700 mcg/day RAE (5,667 International Units/day) PO.
4 to 8 years: 900 mcg/day RAE (3,000 International Units/day) PO.
1 to 3 years: 600 mcg/day RAE (2,000 International Units/day) PO.

600 mcg/day RAE (2,000 International Units/day) PO.

600 mcg/day RAE (2,000 International Units/day) PO.

Two forms of vitamin A are available in the human diet: preformed vitamin A (retinol and its esterified form, retinyl ester) and provitamin A carotenoids. Preformed vitamin A is found in foods from animal sources, including dairy products, fish, and meat (especially liver). The most important provitamin A carotenoid is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin. The body converts these plant pigments into vitamin A. Both provitamin A and preformed vitamin A must be metabolized intracellularly to retinal and retinoic acid, the active forms of vitamin A, to support the vitamin's important biological functions.[63698]
 
Vitamin A has critical roles in proper vision, epithelial cell integrity, and regulation of glycoprotein synthesis and cell differentiation. Vitamin A acts as a cofactor in mucopolysaccharide synthesis, cholesterol synthesis, and the metabolism of hydroxysteroids. Retinal, which is synthesized from retinol, combines with opsin in the retina to form rhodopsin, which is needed for night vision. Vitamin A deficiency is well known to cause xerophthalmia. Through activation of retinoic acid (RAR) and retinoid X (RXR) receptors on epithelial cells, retinoic acid regulates the expression of various genes responsible for structural proteins, enzymes, extracellular matrix proteins, and retinol binding proteins and receptors. Retinol and retinoic acid are also needed for bone development, testicular and ovarian function, embryonic development, and maintenance of mucosal and epithelial surfaces. Dysfunctional storage and transport of vitamin A can occur in some diseases.[52044]
 
Because of its action on free radicals, vitamin A is considered an antioxidant. A study of more than 89,000 female nurses from 1980-1989 showed that women in the top 20% for vitamin A intake were significantly less likely to develop breast cancer than were women in the bottom 20%.[23577] It is believed that the ability of vitamin A to scavenge free radicals may somehow be responsible for reducing the risk of developing some types of cancers.

Vitamin A is administered orally and intramuscularly. Retinol is stored primarily in the liver (greater than 90% when vitamin A intake is adequate), with small amounts distributed to the kidneys, lungs, adrenals, retina, and intraperitoneal fat. Normal serum levels of retinol are 300 to 700 ng/mL in adults. Serum concentrations of retinol are under tight controls and are generally not dependent upon vitamin A liver stores. When vitamin A liver stores fall below 20 mcg/g of liver, the plasma retinol concentration decreases. Therefore, while low retinol concentrations may indicate inadequate vitamin A status, normal concentrations may not correlate with true vitamin A status.
 
Release of retinol from the liver to plasma requires zinc and protein. Most plasma retinol is bound to retinol-binding protein (RBP). Toxic effects of vitamin A occur after storage sites are saturated and the binding capacity of RBP is exceeded. Retinol is metabolized in the liver and other tissues to retinoic acid through a 2-step oxidative process. Retinoic acid is metabolized primarily via cytochrome P450 (CYP) enzymes. Retinoic acid metabolites formed via glucuronidation are excreted in the urine and bile. The amount of vitamin A excreted in the bile increases as the levels of vitamin A within the liver exceed critical levels.
 
Affected cytochrome P450 isoenzymes: CYP26A1, CYP26B1, CYP26C1, and CYP2E1
Retinoic acid is metabolized primarily via cytochrome P450 (CYP) enzymes CYP26A1, CYP26B1, and CYP26C1; however, CYP26A1 is the primary regulator of serum retinoic acid levels and catabolism. Other CYP enzymes have a role in retinoic acid metabolism, notably is CYP2E1, which is alcohol-induced and plays a major role in the breakdown of retinoic acid after exposure to alcohol. Other CYP enzymes have been identified in vitro to influence the metabolism of retinoic acid but the clinical implications are not clear; these CYP enzymes include: CYP2C8, 2C9, 1A2, 2A4, 2A6, 1B1, 2B6, 2C3, 2C7, 2D6, 2E2, 2G1, 3A4/5, 3A6, 3A7, and 4A11.

In the presence of bile salts, pancreatic lipase, and dietary fat, vitamin A is readily absorbed from the GI tract, resulting in 70% to 90% of the dose absorbed. Retinol esters are hydrolyzed by pancreatic enzymes in the GI lumen, with subsequent absorption and reesterification. Carotenoids (i.e., beta-carotene) are absorbed into the small intestine by passive diffusion. Absorption has been estimated at 9% to 22%, although this decreases as the amount ingested increases.[52044] [53845]

Vitamin A in excess of the recommended dietary allowance (RDA) may cause fetal harm when administered during pregnancy and is contraindicated in women who are or may become pregnant. Safety of amounts exceeding 1,800 mcg RAE (6,000 International Units) of vitamin A daily during pregnancy has not been established at this time. If vitamin A is used during pregnancy, or if the patient becomes pregnant while taking vitamin A, the patient should be informed of the potential risk to the fetus. Fetal abnormalities (i.e., craniofacial, neural tube, musculoskeletal, urogenital), growth retardation, and early epiphyseal closure have been reported in children whose mothers took excessive amounts of vitamin A during pregnancy. In a screening of over 22,000 pregnant women, the incidence of birth defects was significantly higher in women ingesting 4,500 mcg RAE (15,000 International Units) or more per day from food and supplements. The prevalence ratio was 3.5 (95% CI: 1.7 to 7.3) for defects associated with cranial-neural-crest tissue for babies born to women who consumed more than 4,500 mcg/day RAE (15,000 International Units/day) compared with babies born to women who consumed 1,500 mcg RAE (5,000 International Units) or less per day. For all birth defects combined, the prevalence ratio was 2.2 (95% CI: 1.3 to 3.8). For supplements alone, the prevalence ratio was 4.8 (95% CI: 2.2 to 10.5) for babies born to women who consumed more than 3,000 mcg/day RAE (10,000 International Units/day) compared with babies born to women who consumed 1,500 mcg RAE (5,000 International Units) or less per day. The increased frequency of defects was concentrated among the babies born to women who consumed high levels of vitamin A before the seventh week of gestation. Although the mean vitamin A intake in the highest group was 6,500 mcg/day RAE (21,675 International Units/day), the authors reported a sharp upswing in prevalence ratio of birth defects between 3,000 and 4,500 mcg/day RAE (10,000 and 15,000 International Units/day). The dosage limits presented here pertain to pre-formed vitamin A and not to beta-carotene.

Use of vitamin A within the recommended daily dietary intake is generally recognized as safe for lactating women who are breast-feeding. Vitamin A, like other fat-soluble vitamins, is transported into the breast milk via fat cells. Because vitamin A is stored in tissues, the impact of excessive vitamin A supplementation on human milk concentrations is not easily measured; milk concentrations of vitamin A do not appear to increase until a significant change occurs in tissue stores.