Composition of Isotretinoin
Isotretinoin (13-cis-retinoic acid) is a retinoid derivative of vitamin A with the chemical formula C20H28O2 and a molecular weight of 300.44. 1
Chemical Structure and Composition
Isotretinoin is chemically identified as (2Z, 4E, 6E, 8E)-3,7-Dimethyl-9-(2,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoic acid 2. It appears as a yellow to orange crystalline powder 1.
Active Ingredient
- 13-cis-retinoic acid
Inactive Ingredients in Commercial Formulations
Isotretinoin capsules typically contain the following inactive ingredients 1:
- Butylated hydroxyanisole
- Edetate disodium dihydrate
- Gelatin
- Glycerin
- Hydrogenated vegetable oil
- Purified water
- Soybean oil
- Titanium dioxide
- White wax (beeswax)
Different dosage strengths may contain additional colorants:
- 10 mg capsules: iron oxide black and iron oxide yellow
- 20 mg capsules: iron oxide black, iron oxide red, and iron oxide yellow
- 30 mg capsules: FD&C yellow #6 aluminum lake
- 40 mg capsules: FD&C yellow #6 aluminum lake
Pharmacological Properties
Isotretinoin is highly lipophilic, which affects its absorption characteristics. Its oral absorption is significantly enhanced when taken with a high-fat meal 1. When administered in pharmacologic dosages of 0.5 to 1 mg/kg/day, isotretinoin:
- Reduces sebaceous gland size
- Decreases sebum production
- Inhibits sebaceous gland differentiation
- Normalizes keratinocyte keratinization
- Possesses anti-inflammatory properties 3
Metabolism
After oral administration, isotretinoin is metabolized into at least three identified metabolites in human plasma 1:
- 4-oxo-isotretinoin
- Retinoic acid (tretinoin)
- 4-oxo-retinoic acid (4-oxo-tretinoin)
Isotretinoin and retinoic acid are geometric isomers that show reversible interconversion. The drug is also irreversibly oxidized to 4-oxo-isotretinoin, which forms its geometric isomer 4-oxo-tretinoin 1.
Protein Binding and Distribution
Isotretinoin is more than 99.9% bound to plasma proteins, primarily albumin 1.
Clinical Significance
Isotretinoin is the only FDA-approved treatment for severe recalcitrant nodular acne vulgaris since 1982 3. It has remarkable effectiveness in clinical practice, producing 60-95% clearance of inflammatory lesions in patients with severe acne when administered at 1-2 mg/kg/day for 3-4 months 4, 2.
Important Considerations
- Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless effective contraception is used 4
- Common adverse effects involve the mucocutaneous, musculoskeletal, and ophthalmic systems 3
- Laboratory monitoring during treatment should include liver function tests, fasting lipid panel, and pregnancy tests for patients with pregnancy potential 3
Understanding the chemical composition and properties of isotretinoin is essential for proper administration and management of potential side effects in patients receiving this medication for severe acne or other dermatological conditions.