VITAMIN A SOLUBILIZED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITAMIN A SOLUBILIZED (VITAMIN A SOLUBILIZED).
Vitamin A (retinol) is essential for vision, immune function, and cellular differentiation. It binds to nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), regulating gene transcription. In the retina, it forms rhodopsin, a light-sensitive pigment necessary for low-light vision.
| Metabolism | Primarily hepatic; hydrolyzed to retinol, then oxidized to retinal and retinoic acid by alcohol dehydrogenases and retinaldehyde dehydrogenases. Conjugated with glucuronic acid and excreted in bile. |
| Excretion | Renal: <1% as unchanged drug; biliary/fecal: >90% as metabolites and conjugated forms. |
| Half-life | Terminal half-life: 12.5–60 days (mean ~25 days) in adults; prolonged in hypervitaminosis A. Clinical context: Accumulation risk with chronic use due to slow elimination. |
| Protein binding | 95–97% bound to retinol-binding protein (RBP) and transthyretin (TTR); in hypervitaminosis, unbound fraction increases. |
| Volume of Distribution | Vd: 0.12–0.19 L/kg (low, reflects extensive plasma protein binding and limited extravascular distribution). Clinical meaning: Reflects restricted distribution; indicates drug remains largely in plasma and liver. |
| Bioavailability | Oral: 70–90% under normal conditions (higher with dietary fat; lower in malabsorption); IM: 100%. |
| Onset of Action | Oral: 3–4 weeks for normalization of serum retinol in deficiency; IM: 1–2 weeks for resolution of deficiency symptoms; topical: 2–4 weeks for improvement in skin conditions (e.g., acne). |
| Duration of Action | Oral: Several weeks to months after single dose (stores in liver); IM: 2–4 weeks; topical: Effects persist up to 4 weeks after discontinuation. Clinical note: Duration depends on hepatic storage capacity. |
| Molecular Weight | 286.45 |
Vitamin A solubilized: 10,000-50,000 IU orally once daily for deficiency. For severe deficiency: 100,000 IU intramuscularly once, repeated in 24 hours if needed. Maintenance: 10,000-20,000 IU orally daily.
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based dose adjustment required. Caution in patients with renal impairment due to risk of hypervitaminosis A. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or reduce dose by 75% with close monitoring. |
| Pediatric use | Children 1-8 years: 5,000-15,000 IU orally daily. Infants: 1,500-5,000 IU orally daily. Severe deficiency: 50,000 IU intramuscularly as a single dose. |
| Geriatric use | No specific dose adjustment. Monitor for toxicity due to potential age-related decline in hepatic clearance. Start at lower end of adult dosing range. |
| 1st trimester | Excessive intake (>10,000 IU/day) is teratogenic; recommended maximum 5,000 IU/day. Therapeutic doses for deficiency should be closely monitored. |
| 2nd trimester | Avoid high doses (>10,000 IU/day) due to risk of fetal toxicity. Recommended daily allowance (RDA) is 770 mcg RAE (2,565 IU). |
| 3rd trimester | Avoid excessive intake; RDA is 1,300 mcg RAE (4,330 IU). High doses may lead to neonatal hypervitaminosis A. |
Clinical note
Comprehensive clinical and safety monograph for VITAMIN A SOLUBILIZED (VITAMIN A SOLUBILIZED).
| Placental transfer | Vitamin A crosses the placenta; excessive levels are associated with teratogenicity. Transfer is dose-dependent and increases with maternal intake. |
| Breastfeeding | Vitamin A is excreted in breast milk. Excessive maternal intake (e.g., >10,000 IU/day) may cause hypervitaminosis A in the infant. RDA during lactation is 1,300 mcg RAE (4,330 IU). Caution with high-dose supplements. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypervitaminosis AKnown hypersensitivity to vitamin A or excipients
| Precautions | Hypervitaminosis A (toxicity) with high doses: hepatotoxicity, intracranial hypertension, teratogenicity. Avoid in pregnancy (except for deficiency). Monitor liver function. Caution in patients with renal impairment or hyperlipidemia. |
| Food/Dietary | Avoid high-dose vitamin A from dietary sources (e.g., liver, cod liver oil) during therapy to prevent toxicity. Alcohol consumption may exacerbate hepatotoxicity. No specific restriction with normal dietary intake; fat-containing meals may enhance absorption of solubilized vitamin A. |
Loading safety data…
| Lactation Rating | L2 (Probably Compatible) for recommended doses; L3 (Moderately Safe) for high doses. |
| Teratogenic Risk | Vitamin A is teratogenic at high doses (≥10,000 IU/day). First trimester: risk of CNS, cardiovascular, and craniofacial malformations. Second/third trimester: fetal toxicity including hydrocephalus and premature epiphyseal closure. Avoid excess supplementation; recommended prenatal dose ≤5,000 IU/day. |
| Fetal Monitoring | Monitor maternal serum retinol levels if excess intake suspected. Fetal ultrasound for malformations if high-dose exposure. Assess infant for bulging fontanelle, irritability, or hepatomegaly. |
| Fertility Effects | Vitamin A is essential for spermatogenesis and ovulation. Both deficiency and excess (hypervitaminosis A) can impair fertility. Adequate intake supports normal reproductive function. |
| Clinical Pearls |
| Monitor for signs of hypervitaminosis A (e.g., pseudotumor cerebri, hepatotoxicity, bone pain) in patients receiving high doses (≥25,000 IU/day). Avoid concurrent use with other retinoids (e.g., isotretinoin) due to additive toxicity. Use with caution in patients with hepatic or renal impairment. Pregnancy category X: teratogenic; discontinue at least 2 weeks before attempted conception. For deficiency, replete slowly to avoid refeeding syndrome. Use water-miscible (solubilized) forms in malabsorption syndromes. Efficacy in measles infection is established: give 200,000 IU PO for 2 doses in infants ≥12 months (50,000 IU for <6 months). |
| Patient Advice | Take vitamin A exactly as prescribed; do not exceed the recommended dose. · Avoid taking additional vitamin A supplements or multivitamins containing vitamin A unless approved by your doctor. · Inform your healthcare provider if you are pregnant, planning to become pregnant, or breastfeeding. · Store at room temperature away from light and moisture. · Contact your doctor if you experience symptoms of toxicity: severe headache, blurred vision, bone pain, skin changes, or nausea/vomiting. |