VITAMIN A
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITAMIN A (VITAMIN A).
Vitamin A (retinol) is converted to retinal and retinoic acid, which bind to nuclear receptors (RARs and RXRs) to regulate gene expression involved in cell growth, differentiation, and vision.
| Metabolism | Hepatic metabolism; retinol is oxidized to retinal by retinol dehydrogenases, then to retinoic acid by retinal dehydrogenases; conjugated with glucuronic acid and excreted in bile. |
| Excretion | Vitamin A is eliminated primarily via biliary excretion into feces as metabolites (approximately 80–90%), with renal excretion accounting for less than 10% of unchanged drug and metabolites. A small fraction undergoes enterohepatic circulation. |
| Half-life | The terminal elimination half-life of vitamin A is variable, ranging from 10 to 100 days due to extensive storage in the liver; in individuals with adequate hepatic stores, the half-life is approximately 50–100 days, but in deficiency states, it may be shorter (10–20 days). Clinically, this long half-life supports once-daily dosing for chronic therapy. |
| Protein binding | Approximately 95% bound to retinol-binding protein (RBP) in plasma; also binds to transthyretin (TTR) in a complex with RBP. |
| Volume of Distribution | Apparent volume of distribution is 0.05–0.2 L/kg, reflecting extensive storage in the liver (90% of body stores) and limited distribution in other tissues. This low Vd indicates sequestration in hepatic and fat stores. |
| Bioavailability | Oral: bioavailability of vitamin A from food sources is 70–90% when consumed with fat; for supplemental forms (retinyl palmitate or acetate), absorption is 70–90%. Topical: systemic absorption is negligible (<5%) with normal application. Intramuscular: not applicable; intravenous formulations are not used due to high toxicity. |
| Onset of Action | Oral: clinical improvement in deficiency symptoms (e.g., night blindness) occurs within 24–72 hours, with normalization of serum retinol levels at 1–2 weeks. Intramuscular (if applicable): not commonly used; topical: improvement in skin conditions may take 2–4 weeks. |
| Duration of Action | Duration of effect is weeks to months due to hepatic storage; a single large dose (e.g., 200,000 IU) can maintain adequate retinol levels for 4–6 months in deficiency. For continuous therapy, effects persist for the duration of treatment. |
Adults: 10000-50000 IU/day orally for deficiency; up to 100000 IU/day for severe deficiency short-term. Intramuscular: 50000 IU daily for 3 days, then 50000 IU weekly for 2-3 months.
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based dose adjustment required; use caution in chronic kidney disease due to risk of hypervitaminosis A. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: reduce dose by 50% and monitor serum retinyl esters. |
| Pediatric use | Deficiency: 5000-10000 IU/kg/day orally for 2-4 weeks; maintenance: 3000-10000 IU/day depending on age. Prophylaxis: 1000-5000 IU/day. |
| Geriatric use | Use lowest effective dose; monitor for hepatotoxicity and bone mineral density loss; recommended daily allowance 700-900 mcg/day (2330-3000 IU/day). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VITAMIN A (VITAMIN A).
| Breastfeeding | Vitamin A is excreted into breast milk in low amounts. Milk-to-plasma ratio approximately 0.5. Low doses (≤5,000 IU/day) are safe; high doses may cause toxicity in infant. Avoid excessive supplementation. |
| Teratogenic Risk | Pregnancy category X. High-dose vitamin A (≥10,000 IU/day) is teratogenic in first trimester, causing CNS, cardiovascular, and craniofacial defects. Isotretinoin (metabolite) has established human teratogenicity. Therapeutic doses (≤5,000 IU/day) have minimal risk, but caution is advised throughout pregnancy. Third trimester: maternal toxicity at excess doses may affect fetus. |
■ FDA Black Box Warning
No FDA boxed warning specific to vitamin A; however, high doses (>10,000 IU/day) are associated with teratogenicity.
| Common Effects | Injection site reactions pain swelling redness |
| Serious Effects |
Hypersensitivity to vitamin A; hypervitaminosis A; pregnancy (high doses); concurrent use with other retinoids (e.g., isotretinoin).
| Precautions | Hypervitaminosis A (toxicity) causing liver damage, intracranial hypertension, bone abnormalities; teratogenicity in pregnancy; avoid in patients with hyperlipidemia, renal impairment, or liver disease. |
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| Fetal Monitoring | Monitor serum retinol levels if high-dose therapy is required. Assess for signs of toxicity (e.g., headache, nausea, hepatotoxicity). Fetal ultrasound for congenital anomalies if high dose exposure occurred in first trimester. |
| Fertility Effects | No adverse effects on fertility at recommended doses. Excess vitamin A may disrupt menstrual cycle; hypervitaminosis A can impair fertility in both sexes. |