Drug reference

Tretinoin

Retinoid · Antineoplastic

Also known as ATRA, all-trans-retinoic acid

RetinoidAntineoplastic

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Teratogenic; Avoid in pregnancy

FDA category + note

Top interactionssee all 12 →

Antifungal ImidazolesSevereTextbookG&G 14e
AcitretinSevereDatabaseDDInter
Aminocaproic AcidSevereDatabaseDDInter
Aminolevulinic AcidSevereDatabaseDDInter

Mechanism

Tretinoin (all-trans retinoic acid) binds to and activates retinoic acid receptors (RAR-α, β, γ) that heterodimerize with RXR to regulate gene transcription controlling cellular differentiation and proliferation. In acute promyelocytic leukemia (APL), the PML-RAR-α fusion oncoprotein blocks myeloid differentiation; pharmacological doses of tretinoin overcome this block by promoting degradation of the fusion protein and reactivating differentiation of leukemic promyelocytes into mature granulocytes. Topically, it normalizes keratinocyte differentiation, accelerates turnover, and reduces comedone formation.

Indications

Acute promyelocytic leukaemia (in combination with arsenic trioxide)Acute promyelocytic leukemia (APL)Acute promyelocytic leukaemia (APL)Acne vulgarisPrevention of photoageing of skin (dry scaly surface, mottling, wrinkles, rough/leathery texture, sagging, pigmented spots)Acne (topical)

Dosing

Adult: exceeds 1 g, or 109 cells, and each cycle of therapy kills. CHAPTER 60 GENERAL PRINCIPLES OF CANCER CHEMOTHERAPY

Pharmacokinetics

Half-life

Less than 1 h

Excretion

Cleared by a CYP3A4-mediated elimination.

Contraindications

Pregnancy (teratogenic and embryotoxic)
Pregnancy (use only if essential, due to minor but present teratogenic risk)

Side effects

Common

Dry skinCheilitisReversible hepatic enzyme abnormalitiesBone tendernessPseudotumor cerebriHyperlipidemiaDryness of skin, eye, nose, mouthPruritusEpistaxisRise in serum lipidsHepatic transaminasesIntracranial pressureFeeling of warmthStingingExcessive rednessEdemaCrusting

Serious

Leukocyte maturation syndrome ('retinoic acid differentiation syndrome') (in 15% to 20% of patients, characterized by fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions; responds to corticosteroids and chemotherapy)
Hypercalcemia (responds to diuresis, bisphosphonates, and ATRA discontinuation)
Renal failure (responds to diuresis, bisphosphonates, and ATRA discontinuation)
'Retinoic acid syndrome' (breathlessness, fever, pleural/pericardial effusion, pulmonary infiltrates)

Pregnancy & lactation

Pregnancy

Teratogenic; Avoid in pregnancy

Lactation

Discontinue breast-feeding

Drug interactions

Antifungal Imidazoles

Severe

Textbook

Block tretinoin degradation, potentially leading to hypercalcemia and renal failure.

Monitor for hypercalcemia and renal function. Manage hypercalcemia with diuresis and bisphosphonates. Discontinue tretinoin if severe toxicity occurs. Avoid co-administration if possible or monitor closely.

Source: G&G 14e

Acitretin

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Aminocaproic Acid

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Aminolevulinic Acid