TRETINOIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Retinoic acid receptor agonist; binds to RAR and RXR nuclear receptors, modulating gene transcription involved in cell differentiation, proliferation, and apoptosis.
| Metabolism | Hepatic via CYP450 enzymes (CYP2C8, CYP2C9, CYP2B2, CYP2E1) to metabolites including 4-oxo-tretinoin and retinoic acid glucuronide. |
| Excretion | Primarily fecal (approx. 60%) via biliary excretion as metabolites; renal excretion accounts for <15% of a dose as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is 0.5-2 hours for the parent drug, but may be prolonged to 10-12 hours after multiple dosing due to reduced clearance; clinical context: t1/2 is short, requiring frequent or continuous dosing to maintain therapeutic levels. |
| Protein binding | >95% bound, primarily to albumin. |
| Volume of Distribution | Approximately 1.5-3 L/kg, indicating extensive tissue distribution and accumulation in tissues such as skin and liver. |
| Bioavailability | Oral: approximately 50% (range 30-70%) due to first-pass metabolism. Topical: systemic absorption is minimal (less than 5% of applied dose) but can increase with damaged skin barrier. |
| Onset of Action | Topical: 2-4 weeks for clinical improvement in acne. Oral: 4-8 weeks for remission induction in acute promyelocytic leukemia (APL). |
| Duration of Action | Topical: Effects persist for weeks after discontinuation; clinical improvement continues after treatment cessation. Oral: Duration is sustained during treatment; relapse may occur if therapy is stopped prematurely in APL. |
Acute promyelocytic leukemia (APL): 45 mg/m2/day orally divided twice daily, as induction therapy.
| Dosage form | CREAM |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (eGFR <30 mL/min/1.73 m2) due to limited data. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: avoid use or reduce dose by 50% with close monitoring. |
| Pediatric use | APL: 45 mg/m2/day orally divided twice daily. Capsules should not be used in children who cannot swallow whole capsules; alternative formulations may be considered. |
| Geriatric use | No specific dose adjustment; monitor for renal function and tolerability, as elderly may be more susceptible to adverse effects such as hypertriglyceridemia and pseudotumor cerebri. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Highly teratogenic and can cause severe skin irritation.
| Breastfeeding | Contraindicated during breastfeeding due to potential for infant exposure and adverse effects. Tretinoin is excreted into human milk; M/P ratio not quantified. Oral tretinoin may cause retinoid-related toxicities in nursing infants. |
| Teratogenic Risk | Pregnancy category C (oral); category D (topical high dose). First trimester: High risk of major congenital malformations including CNS, cardiovascular, craniofacial defects, and thymic aplasia (retinoid embryopathy). Second/third trimester: Risk of spontaneous abortion, fetal growth restriction, and neurodevelopmental impairment. Systemic absorption from topical use is low but cases of embryopathy reported with excessive application or compromised skin barrier. |
■ FDA Black Box Warning
Tretinoin can cause fetal harm when administered to pregnant women. If used during pregnancy or if patient becomes pregnant while taking this drug, apprise of potential hazard to the fetus.
| Common Effects | Skin dryness |
| Serious Effects |
Pregnancy, hypersensitivity to tretinoin or any component of the formulation, breastfeeding (relative).
| Precautions | Risk of teratogenicity; women of childbearing potential must use effective contraception. Retinoic acid syndrome (fever, dyspnea, pulmonary infiltrates) may occur in APL treatment. Hepatotoxicity, hypertriglyceridemia, pseudotumor cerebri. |
Loading safety data…
| Fetal Monitoring | Monitor pregnancy status before initiation and monthly during therapy (negative pregnancy test required). For women of childbearing potential: two effective contraceptive methods. During pregnancy: serial ultrasounds for fetal growth and anatomy; fetal echocardiography between 18-22 weeks. Monitor maternal liver function, triglycerides, and signs of pseudotumor cerebri. |
| Fertility Effects | No direct impairment of fertility in animal studies. In humans, tretinoin may cause reversible menstrual irregularities. No evidence of long-term fertility effects. |