Vitamin A

Introduction Overview

Generic Name

vitamin A

Brand Name

Aquasol A, A-25, A/Fish Oil, Xcellent A 3000, Xcellent A 7500

Dosage Form

intramuscular solution, oral capsule

Drug Class

Vitamins

Pharmacokinetics

Absorption:
Vitamin A is a fat-soluble vitamin that is absorbed primarily in the small intestine along with dietary fats. The efficiency of absorption depends on the presence of bile salts and pancreatic enzymes, which facilitate the micellar solubilization of vitamin A and its provitamin carotenoids. Conditions impairing fat absorption, such as cystic fibrosis, pancreatic insufficiency, celiac disease, or short gut syndrome, significantly reduce vitamin A uptake. Oral intake with fatty meals enhances absorption, while agents that impair fat absorption, such as orlistat or mineral oil, can markedly decrease bioavailability. Absorbed vitamin A is incorporated into chylomicrons for lymphatic transport.

Distribution:
Following absorption, vitamin A is distributed via the lymphatic system and systemic circulation predominantly bound to retinol-binding protein (RBP) and transthyretin in plasma. It is stored mainly in the liver, which acts as the major reservoir regulating serum vitamin A levels and releasing it as needed. Smaller amounts are stored in adipose tissue and other organs. The distribution to target tissues, such as the retina, skin, and immune cells, facilitates its biological actions. The lipophilic nature allows accumulation in fatty tissues, which contributes to a relatively large storage pool. Plasma half-life is maintained through a homeostatic mechanism controlling transport and delivery.

Metabolism:
Vitamin A metabolism involves conversion between various active and storage forms. Dietary retinyl esters are hydrolyzed to retinol which can be oxidized to retinaldehyde and retinoic acid, the biologically active metabolite that modulates gene expression through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Retinoic acid is further metabolized via cytochrome P450 enzymes (mainly CYP26) to inactive metabolites for excretion. Excess vitamin A is esterified and stored as retinyl esters primarily in hepatic stellate cells. Metabolic pathways are tightly regulated to maintain homeostasis and prevent toxicity.

Elimination:
Elimination occurs primarily via biliary excretion into the feces; only a minor fraction is excreted in urine. The half-life of vitamin A ranges from several hours to days depending on the form and physiological status. Excess vitamin A can accumulate due to its fat-soluble nature, increasing the risk of toxicity with chronic overdose. The enterohepatic circulation recycles vitamin A metabolites, prolonging systemic availability. Excretion pathways ensure tight regulation to avoid hypervitaminosis A. Liver dysfunction may impair elimination and exacerbate toxicity risk.

Dosage Forms

Available Dosage Forms:
Vitamin A is available as:
- Intramuscular solution: 50000 units/mL
- Oral capsules: 10000 international units (IU), 2400 mcg, 3000 mcg, and 7500 mcg

Dosages for Adults and Adolescents:
Dosage varies based on indication and patient needs. For treatment of vitamin A deficiency, oral doses typically range from 5000 to 10000 IU daily or as prescribed by a healthcare provider. Intramuscular injections may be administered for rapid repletion, especially when oral administration is not feasible, typically using 50000 IU/mL formulations. The recommended dietary allowance (RDA) increases with age and physiological status (e.g., pregnancy). High doses must be cautiously used due to toxicity risk.

Specific Patient Populations:
In children, dosing is weight- and age-dependent; healthcare providers tailor doses carefully to avoid toxicity while ensuring adequacy for growth and development. Pregnant women require careful dose adjustment to prevent birth defects associated with excess vitamin A. Patients with malabsorption syndromes (celiac disease, cystic fibrosis, short gut syndrome) may require higher or parenteral dosing. Patients with liver or kidney impairment should be monitored closely. Breastfeeding patients may require dose adjustment to optimize infant nutrition while preventing toxicity.

Mechanism Of Action

Vitamin A exerts its biological effects primarily through its active metabolite, retinoic acid, which regulates gene transcription by binding to nuclear receptors in target cells. These retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers that bind to retinoic acid response elements (RAREs) in the DNA, modulating expression of genes critical for cell differentiation, proliferation, and apoptosis.

At the cellular level, vitamin A is essential for maintaining epithelial tissue integrity, immune function, and vision. Retinal, another metabolite, is crucial for phototransduction as a component of rhodopsin in retinal rod cells, enabling low-light vision. Vitamin A also influences hematopoiesis, embryogenesis, and skin health by regulating keratinocyte differentiation.

Biochemically, vitamin A participates in antioxidant activity and modulates intercellular communication pathways, contributing to immune response and mucosal barrier maintenance. Its mechanism parallels other fat-soluble vitamins but is unique in regulating gene expression directly, unlike vitamins with primarily enzymatic cofactor roles.

Clinically, the modulation of gene transcription underlies vitamin A’s therapeutic effects in deficiency states, retinitis pigmentosa, and possibly cataract prevention. Its role in cellular differentiation supports investigations into its use in dermatological conditions and cancer therapy. Comparative studies demonstrate differences from other fat-soluble vitamins; vitamin A’s nuclear receptor-mediated actions position it as a critical regulator of developmental and homeostatic processes.

Pharmacological Actions

Essential nutrient for vision through retinal, a component of rhodopsin.
Regulates gene expression via retinoic acid binding to nuclear receptors.
Maintains epithelial tissue integrity and promotes skin health.
Supports immune system function and mucosal barrier maintenance.
Facilitates normal growth and embryonic development.
Exhibits antioxidant properties protecting cells from oxidative damage.
Modulates differentiation and proliferation of various cell types.
Enhances hematopoiesis and supports red blood cell formation.
Involved in maintenance and repair of mucous membranes.
Supports reproductive health and fetal development.
Helps prevent xerophthalmia and night blindness caused by deficiency.
May slow progression of retinitis pigmentosa by preserving retinal function.
Potential protective effects against cataract formation.
Participates in regulating neurological functions and cognitive performance.
Intervenes in skin repair mechanisms in dermatological therapies.

Therapeutic Or Clinical Uses

Treatment and prevention of vitamin A deficiency.
Management of xerophthalmia and night blindness.
Adjunct therapy for retinitis pigmentosa to slow disease progression.
Supportive treatment in malnourished pregnant women to prevent diarrhea.
Nutritional supplementation in conditions with malabsorption (e.g., cystic fibrosis, celiac disease).
Use in hepatic retinol deficiency states.
Prevention of blindness in populations at risk for vitamin A deficiency.
Potential use in dermatological conditions demanding keratinocyte regulation.
Supportive role in immune function enhancement, particularly in infectious diseases.
Treatment of neonatal vitamin A deficiency in certain cases.
Adjunct in growth retardation due to nutritional deficiencies.
Use in bone remodeling processes, cautiously due to fracture risk at high doses.
Supportive therapy in anemia linked to vitamin A deficiency.
Experimental use in some cancers and skin disorders under clinical study.
Prophylaxis in populations with limited dietary vitamin A intake.

Side Or Adverse Effects

Headache and dizziness indicative of acute toxicity.
Severe drowsiness, loss of consciousness in high doses, especially children.
Vomiting, diarrhea, and loss of appetite during overdose.
Mood changes including irritability and confusion.
Double vision and vision disturbances due to intracranial hypertension.
Bleeding gums and mouth pain linked to mucosal toxicity.
Hair loss, peeling and cracked skin particularly around mouth.
Skin discoloration and photosensitivity reactions.
Increased risk of osteoporosis and hip fractures with prolonged high-dose use, especially in older adults and postmenopausal women.
Fever, sweating, and unusual tiredness as systemic toxicity signs.
Seizures in severe cases of toxicity.
Respiratory symptoms in children such as cough with mucus, chest pain, and trouble breathing.
Changes in menstrual periods indicating endocrine effects.
Yellowing of skin or eyes (jaundice) suggestive of liver toxicity.
Allergic reactions including hives, swelling of the face, lips, tongue, or throat.

Precautions

Use cautiously in patients with liver disease or impaired hepatic function.
Avoid use without medical supervision during pregnancy due to teratogenic risk.
Careful dosing required in children to prevent growth disturbances and toxicity.
Monitor patients with zinc or iron deficiencies as absorption may be impaired.
Patients with malabsorption syndromes require assessment for adequate dosing.
Avoid concomitant use of orlistat or mineral oil that impair absorption.
Dose adjustments may be necessary during breastfeeding.
Avoid excess intake and multiple vitamin products concurrently to prevent overdose.
Regular monitoring for signs of toxicity in long-term use or high-dose therapy.
Use with caution in patients with kidney disorders.
Evaluate nutritional status to prevent unnecessary supplementation.
Consider potential drug interactions, especially with retinoids and tetracycline antibiotics.
Discontinue if signs of hypersensitivity occur.
Educate patients on signs of toxicity and when to seek medical attention.
Avoid alcohol consumption to reduce risk of liver toxicity.

Warnings

Do not exceed recommended doses; overdose can cause serious or life-threatening side effects.
Avoid vitamin A use in pregnancy without medical advice due to risk of birth defects.
High doses increase risk of osteoporosis and hip fracture, especially in older adults.
Overdose symptoms include dizziness, drowsiness, vision changes, headache, vomiting, dark urine, and jaundice.
Risk of intracranial hypertension and its neurological complications with excessive intake.
Avoid simultaneous use of multiple vitamin A containing products to prevent toxicity.
Use cautiously in patients with hepatic or renal impairment due to altered metabolism and elimination.
Vitamin A toxicity can be insidious and accumulate with chronic excessive intake.
Abrupt discontinuation after prolonged high-dose therapy requires medical supervision.
Vitamin A supplements should not replace a balanced diet unless deficiency is diagnosed.
Use injection forms only under medical supervision and when oral administration is not possible.
Risk of allergic reactions including anaphylaxis.
In children, high doses can cause severe central nervous system and developmental adverse effects.
Avoid concurrent use with retinoids which can potentiate toxicity.
Patients should be monitored for mucocutaneous and systemic toxicities.

Contraindication

Known hypersensitivity to vitamin A or any component of the formulation.
Use in pregnancy without strict medical supervision due to teratogenic risk.
Patients with pre-existing hypervitaminosis A or vitamin A toxicity.
Concurrent use with other systemic retinoids contraindicated to avoid additive toxicities.
Severe liver disease where accumulation could worsen hepatic function.
Conditions associated with elevated intracranial pressure.
Malabsorption syndromes without medical supervision for appropriate dosing.
Use contraindicated with certain antibiotics such as tetracyclines without physician guidance.
Avoid administration in patients with untreated anemia without correction.
Contraindicated when using excessive doses as dietary supplements without physician oversight.
Patients with vitamin A metabolism disorders.
Injection form contraindicated in those with bleeding disorders that complicate intramuscular administration.
Concurrent use with acitretin or isotretinoin outside of specific medical guidance.
Avoid in patients allergic to any excipients present in the dosage form.
Children should receive only recommended doses; contraindicated in overdosing.

Drug Interactions

Orlistat (alli, Xenical) reduces absorption of vitamin A due to inhibition of fat absorption.
Mineral oil impairs vitamin A absorption when taken concurrently.
Tetracycline antibiotics (doxycycline, minocycline, sarecycline, tetracycline) may increase intracranial pressure risk.
Retinoids including acitretin, isotretinoin, tretinoin, and others can potentiate vitamin A toxicity.
Birth control pills may alter vitamin A metabolism and serum levels.
Concurrent use with corticosteroids may affect vitamin A storage and levels.
Drugs causing malabsorption can reduce vitamin A efficacy.
Hepatotoxic drugs may increase risk of liver injury when administered with vitamin A.
Interactions with anticoagulants require monitoring due to potential bleeding risk from mucosal toxicity.
Other fat-soluble vitamins may compete or synergize affecting vitamin A bioavailability.
Excessive vitamin A may interfere with vitamin D actions influencing calcium homeostasis.
Concurrent alcohol use increases hepatotoxic risk during vitamin A therapy.
Certain anticonvulsants that induce CYP enzymes may increase vitamin A metabolism lowering effectiveness.
Drug interactions may alter vitamin A serum concentrations impacting clinical outcomes.
Supplementation should be planned carefully to avoid interaction-induced toxicity or deficiency.

Preparations Of The Drug

Intramuscular injection solution containing 50000 units/mL for parenteral administration.
Oral capsule formulations available in strengths of 10000 international units, 2400 mcg, 3000 mcg, and 7500 mcg.
Some preparations combined with fish oil or other nutrient supplements.
Available as single-ingredient vitamin A products or as multivitamin formulations.
Parenteral preparations used primarily when oral administration is not feasible or absorbed.
Oral formulations designed to be swallowed whole; not to be chewed or crushed.
Different brands include Aquasol A, A-25, A/Fish Oil, Xcellent A 3000, and Xcellent A 7500.
Various pharmaceutical vehicles to optimize bioavailability and patient tolerability.
Capsules typically contain vitamin A palmitate or acetate forms for stability.
Intramuscular solutions prepared for sterile injection under controlled conditions.
Formulations may vary in specific excipients and flavoring agents.
Dosage forms intended for daily, weekly, or single-dose regimens depending on indication.
Storage conditions require protection from moisture, heat, and light to preserve potency.
Special prenatal vitamin formulations contain adjusted vitamin A levels suitable for pregnancy.
Patient education materials accompany preparations to guide correct administration and avoid toxicity.