vitamin A (retinol)
Aquasol A, Del-Vi-A, Palmitate-A 5000

Available forms
Available by prescription only
Capsules: 25,000 IU
Injection: 2-ml vials (50,000 IU/ml with 0.5% chlorobutanol, polysorbate 80, butylated hydroxyanisole, and butylated hydroxytoluene)
Available without a prescription
Capsules: 10,000 IU, 15,000 IU
Tablets: 5,000 IU

Indications and dosages
 Severe vitamin A deficiency with xerophthalmia. Adults and children older than age 8: 500,000 IU P.O. daily for 3 days. Then 50,000 IU P.O. daily for 14 days. Then maintenance dose of 10,000 to 20,000 IU P.O. daily for 2 months. Then adequate dietary nutrition and RDA vitamin A supplements.
 Severe vitamin A deficiency. Adults and children older than age 8: 100,000 IU P.O. or I.M. daily for 3 days. Then 50,000 IU P.O. or I.M. daily for 14 days. Then maintenance dose of 10,000 to 20,000 IU P.O. daily for 2 months. Then adequate dietary nutrition and RDA vitamin A supplements.
Children ages 1 to 8: 17,500 to 35,000 IU I.M. daily for 10 days.
Infants younger than age 1: 7,500 to 15,000 IU I.M. daily for 10 days.
 RDA for vitamin A.   See following table.

Vitamin A RDA (RE) Vitamin A and beta carotene RDA Infants Birth to 12 months 375 1,875 IU Children Ages 1-3 400 2,000 IU Ages 4-6 500 2,500 IU Ages 7-10 700 3,500 IU Males Age 11 and older 1,000 5,000 IU Females Age 11 and older 800 4,000 IU Pregnant 800 4,000 IU Breast- feeding 1,300 (1st 6 months) 6,500 IU 1,200 (2nd 6 months) 6,000 IU RE = retinol equivalents IU = combination of retinol and beta-carotene

Pharmacodynamics
Metabolic action: One IU of vitamin A is equivalent to 0.3 mcg of retinol or 0.6 mcg of beta carotene. Beta carotene, or provitamin A, yields retinol after absorption from the intestinal tract. Retinol’s use with opsin, the red pigment in the retina, helps form rhodopsin, which is needed for visual adaptation to darkness. Vitamin A prevents growth retardation and preserves the integrity of the epithelial cells. Vitamin A deficiency is characterized by nyctalopia (night blindness), keratomalacia (necrosis of the cornea), keratinization and drying of the skin, low resistance to infection, growth retardation, bone thickening, diminished cortical steroid production, and fetal malformations.

Pharmacokinetics
Absorption: In normal doses, absorbed readily and completely if fat absorption is normal. Larger doses, or regular doses in patients with fat malabsorption, low protein intake, or hepatic or pancreatic disease may be absorbed incompletely. Because vitamin A is fat-soluble, absorption needs bile salts, pancreatic lipase, and dietary fat.
Distribution: Stored (primarily as palmitate) in Kupffer’s cells of liver. Normal adult liver stores are sufficient to provide vitamin A requirements for 2 years. Lesser amounts of retinyl palmitate are stored in kidneys, lungs, adrenal glands, retinas, and intraperitoneal fat. Vitamin A circulates bound to a specific alpha₁ protein, retinol-binding protein (RBP). Blood level assays may not reflect liver storage of vitamin A because serum levels depend partly on circulating RBP. Liver storage should be adequate before therapy ends. Distributed into breast milk; doesn’t readily cross the placental barrier.
Metabolism: Metabolized in liver.
Excretion: Retinol (fat-soluble) is conjugated with glucuronic acid and then further metabolized to retinal and retinoic acid. Retinoic acid is excreted in feces via biliary elimination. Retinal, retinoic acid, and other water-soluble metabolites excreted in urine and feces. Normally, no unchanged retinol excreted in urine, except in patients with pneumonia or chronic nephritis.

Contraindications and precautions
Oral form contraindicated in patients with malabsorption syndrome; if malabsorption is from inadequate bile secretion, oral route may be used with concurrent administration of bile salts (dehydrocholic acid). Also contraindicated in those with hypervitaminosis A and hypersensitivity to any ingredient in product. I.V. route contraindicated except for special water-miscible forms intended for infusion with large parenteral volumes. I.V. push of vitamin A of any type also contraindicated (anaphylaxis or anaphylactoid reactions and death have resulted). Use cautiously in pregnant women.

Interactions
Drug-drug. Cholestyramine, mineral oil (prolonged use), neomycin: Decreases absorption of vitamin A. Avoid use with mineral oil or neomycin. Daily vitamin A supplements have been recommended during long-term cholestyramine therapy.
Hormonal contraceptives: Significantly increases vitamin plasma levels. Adjust vitamin dosage.
Retinoids (such as etretinate, isotretinoin): May cause additive adverse effects. Avoid use together.
Warfarin: Large doses of vitamin A may interfere with hypoprothrombinemic effect of warfarin. Avoid use together.

Adverse reactions
CNS: irritability, headache, increased intracranial pressure, fatigue, lethargy, malaise.
EENT: papilledema, exophthalmos.
GI: anorexia, epigastric pain, vomiting, polydipsia.
GU: hypomenorrhea, polyuria.
Hepatic: jaundice, hepatomegaly, cirrhosis.
Metabolic: hypercalcemia.
Musculoskeletal: slow growth, decalcification, periostitis, premature closure of epiphyses, migratory arthralgia, cortical thickening over the radius and tibia.
Skin: alopecia; dry, cracked, scaly skin; pruritus; lip fissures; erythema; inflamed tongue, lips, and gums; massive desquamation; increased pigmentation; night sweats.
Other: splenomegaly, anaphylaxis.

Effects on lab test results
• May increase liver enzyme levels.

Overdose and treatment
In cases of acute toxicity, a few hours after administration of a dose of 25,000 IU/kg, irritability, drowsiness, vertigo, delirium, coma, vomiting, and diarrhea may occur. Increased intracranial pressure develops within 8 to 12 hours; cutaneous desquamation follows in a few days. Toxicity can follow a single dose of 25,000 IU/kg, which in infants would represent about 75,000 IU and in adults over 2 million IU.
 Chronic toxicity results from administration of 4,000 IU/kg for 6 to 15 months. In infants (ages 3 to 6 months), this would be about 18,500 IU/day for 1 to 3 months; in adults, 1 million IU/day for 3 days, 50,000 IU/day for longer than 18 months, or 500,000 IU/day for 2 months.
 To treat toxicity, stop vitamin A if hypercalcemia persists; administer I.V. saline solution, prednisone, and calcitonin, if indicated. Perform liver function tests to detect possible liver damage.

Special considerations
 ALERT Prescribing, dispensing, and dosing errors have been reported using the abbreviation IU. Take care to write clearly or spell out if possible.
• Adverse reactions usually occur only with toxicity.
• In any dietary deficiency, suspect multiple vitamin deficiency.
• Give vitamin A with bile salts to patients with malabsorption caused by inadequate bile secretion.
 ALERT Vitamin A given by I.V. push is contraindicated; it can cause anaphylaxis and death.
• Use special water-miscible form of vitamin A when adding to large parenteral volumes.
• Vitamin A therapy may falsely increase serum cholesterol level readings by interfering with the Zlatkis-Zak reaction. Vitamin A has also been reported to falsely elevate bilirubin levels.
• Monitor therapeutic effect.
• Monitor patient for adverse effects.
• Patients receiving more than 25,000 IU of vitamin A should be closely supervised.
Pregnant patients
• Safety of amounts exceeding 5,000 IU/day (oral) or 6,000 IU/day (parenteral) during pregnancy is unknown.
Breast-feeding patients
• Vitamin A appears in breast milk. The RDA of vitamin A for breast-feeding women in the United States is 1,300 and 1,200 retinol equivalents for the first 6 months and second 6 months, respectively. Unless the maternal diet is grossly inadequate, infants can usually obtain sufficient vitamin A from breast-feeding. The effect of large maternal doses of vitamin A on breast-fed infants is unknown.
Pediatric patients
• Liquid preparations may be mixed with fruit juice or cereal.
Geriatric patients
• Liquid preparations are available to administer by nasogastric tube.

Patient education
• Explain that patient must avoid prolonged use of mineral oil while taking drug because mineral oil reduces vitamin A absorption in the intestine.
• Tell patient not to exceed recommended dosage.
• Instruct patient to report promptly symptoms of overdose (nausea, vomiting, anorexia, malaise, drying or cracking of skin or lips, irritability, headache, or loss of hair) and to stop drug immediately if they occur.
• Advise patient to consume adequate protein, vitamin E, and zinc, which, along with bile, are needed for vitamin A absorption.
• Tell patient to store vitamin A in a tight, light- resistant container.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use