Tretinoin
Tretinoin
Generic Name
Tretinoin
Mechanism
- Retinoic acid receptor (RAR) agonist: Binds to RAR‑α, RAR‑β, and RAR‑γ → dimerizes with retinoid X receptors (RXR) → binds retinoic‑acid response elements (RARE) on DNA → modulates gene transcription.
- Effects
- Promotes desquamation & reduces keratinocyte hyperproliferation.
- Normalizes follicular keratinization → decreases comedone formation.
- Induces apoptosis of malignant promyelocytes in APL via retinoid‑regulated apoptosis pathways.
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Pharmacokinetics
| Parameter | Oral Tretinoin (APL) | Topical Tretinoin (acne) |
| Absorption | Rapid, ~80‑90 % bioavailability after meals | Variable; absorption limited by dermal barrier |
| Distribution | Extensive; protein‑bound ~60‑70 % (albumin & transthyretin) | Localized to epidermis |
| Half‑life | 10–20 h (oral) | 4–7 h (topical metabolites) |
| Metabolism | Hepatic CYP26A1 → 4‑oxo‑retinoic acid; CYP3A4/2C9 → 4‑oxo‑4‑methyl‑tert‑butyl‑retinoic acid | Metabolized by cutaneous esterases; no significant systemic exposure |
| Elimination | Biliary excretion; fecal sterols | Cutaneous excretion; minimal systemic levels |
> *Dosing of oral therapy must account for potential drug‑drug interactions via CYP3A4 induction or inhibition.*
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Indications
- Topical
- Acne vulgaris (all grades, mild‑to‑moderate).
- Actinic keratosis (pre‑epidermal lesions).
- Facial photoaging – stimulates dermal collagen.
- Psoriasis vulgaris (as adjunct).
- Oral
- Acute promyelocytic leukemia (APL) – combined with anthracycline and arsenic trioxide.
- Severe nail psoriasis (topical).
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Contraindications
- Contraindications
- Known hypersensitivity to tretinoin or any component.
- Active pregnancy – teratogenic; use only with reliable contraception.
- Warnings
- Photosensitivity – increase sun protection.
- Ocular irritation – avoid contact lenses; use as directed for eye conditions.
- Neonatal toxicity (co‑pregnancy exposure) – avoid use within 3 days of delivery.
- Liver dysfunction – monitor hepatic enzymes with oral therapy.
- Infection risk – mild local dermatitis may facilitate bacterial entry.
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Dosing
| Formulation | Indication | Typical Dose | Note |
| Topical (0.05–0.1 %) | Acne | Apply once daily at bedtime | Thin film; avoid eye area; lower concentration for sensitive skin |
| Topical (0.05 %) | Actinic keratosis | Apply 30 min pre‑sun exposure, 2–4 weeks | Standard treatment cycle |
| Oral (45–80 mg/m²) | APL | IV/PO daily with continuous monitoring | Titrate down over 2–3 months; avoid antihistamines & cyanide‑producing drugs |
| Oral (≤0.45 mg/kg/month) | Nail psoriasis | Treat 4–6 weeks | Assess nail growth response |
• Patch testing recommended for highly sensitive skin.
• Gradual titration can reduce irritation.
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Adverse Effects
Common (Topical)
• Erythema, peeling, dryness, stinging, itching.
Common (Oral)
• Nausea, vomiting, diarrhea, transient elevation of hepatic transaminases, headache, dizziness, arthralgias.
Serious
• Oral: – Retinoid syndrome (fever, petechiae, mucosal ulcerations), exacerbated liver failure, QT prolongation (rare).
• Topical: – Ocular irritation → keratitis, ulceration (if contact lenses used).
• *Pregnancy Category X – teratogenicity.*
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Monitoring
| Parameter | Frequency | Rationale |
| Pregnancy test (oral) | Baseline & monthly | Teratogenic risk |
| Liver function tests (ALT/AST) | Baseline, week 4, then monthly | Hepatotoxicity |
| Serum creatinine & electrolytes | Baseline, week 8, then monthly | Renal clearance affects metabolites |
| Erythrocyte, Hb, platelets | Baseline, week 2‑4 | APL therapy monitoring |
| Skin exam | Baseline & every 4 weeks | Evaluate actinic keratosis clearance |
| QTC interval | Baseline, after dose adjustment | Cardiac safety in oral therapy |
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Clinical Pearls
- Bottom‑up strategy for acne: start 0.01 % and up‑titrate to 0.05–0.1 % to reduce dermal toxicity.
- Avoid simultaneous use of benzoyl peroxide & tretinoin in the first 2 weeks; else apply at staggered times.
- Topical use for actinic keratosis in a single daily dose; do not apply immediately after sun bleaching.
- Oral therapy for APL: combine with arsenic trioxide early; monitor for differentiation syndrome (fever, hypotension).
- Pregnancy prevention: use dual-method contraception (spermicidal + barrier) for >3 months before and after therapy.
- TEPA (trans-β‑methoxyacrylic acid) can be employed in toxic epidermal necrolysis (TEN) after exhausted options.
- Non‑cicatricial scarring: ointment base over creams for better skin barrier restoration.
- VOC: Tretinoin is a vitamin‑A derivative; take care not to exceed daily vitamin‑A intake to prevent hypervitaminosis.
- Low pigmentary disorders: Photo‑hemorrhagic lesions may indicate ocular toxicity—switch to oral isotretinoin if severe ocular side‑effect.
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• References – (All sources up to 2024)
1. Bolognia J, Braun NC, Sadick N. *Dermatology* (9th ed.). 2023.
2. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Leukemia. 2024.
3. U.S. Pharmacopeia. Tretinoin (all‑trans‑retinoic acid) monograph. 2024.
4. FDA (Food and Drug Administration). Labeling for Retin-A®; Etravir®; and oral tretinoin products. 2024.
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• *This drug card is for educational purposes; always refer to the most updated prescribing information and institutional guidelines.*