Tretinoin
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.Pregnancy: avoid
Avoid in pregnancy. A potent teratogen (boxed warning): pregnancy must be excluded before and prevented during treatment and for a month after; breastfeeding is not advised.
All-trans retinoic acid taken by mouth for acute promyelocytic leukaemia: it makes the leukaemic cells mature. Watch for differentiation syndrome.
Also called: all-trans retinoic acid (ATRA)
Quick facts
- Group
- Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
- Target
- Retinoic acid receptor α (RARα), part of the PML-RARα fusion in APL
- Used for
- Acute promyelocytic leukaemia
- Key effects
- Headache · Dry skin · Nausea
- Monitor
- Daily weight · White cell count · Coagulation tests
- ATC
- L01XF01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows the ligand-binding domain of human RARα holding retinoic acid, paired with an RXRα domain and a short coactivator peptide; the RXRα partner holds a different, blocking ligand.
In APL the t(15;17) translocation fuses PML to the retinoic acid receptor α. The PML-RARα protein binds retinoids poorly and keeps a repressor on the genes of myeloid maturation, so promyelocytes accumulate. At pharmacological levels tretinoin displaces the repressor, switches on the maturation program and promotes degradation of PML-RARα. Leukaemic promyelocytes mature into neutrophil-like cells, the bleeding tendency of APL improves, and normal blood formation returns.
- t(15;17) makes PML-RARα, which blocks maturation
- High-level tretinoin displaces the repressor
- PML-RARα is degraded; maturation genes switch on
- Promyelocytes mature; bleeding tendency improves
Indications
- Acute promyelocytic leukaemia with t(15;17) or PML-RARα, to induce remission; usually combined with arsenic trioxide or an anthracycline. Acute leukaemia (AML and ALL) →
Adverse effects
Common
- Headache, fever, bone pain
- Dry skin, lips and mucous membranes
- Nausea, vomiting, abdominal pain
- Raised triglycerides and cholesterol
- Raised liver enzymes
- Rising white cell count
Contraindications
- Allergy to tretinoin or other retinoids
Key interactions
- Strong CYP3A inhibitors (e.g. azole antifungals) and inducers
- Avoided: inhibitors raise tretinoin levels and toxicity (including high calcium); inducers lower its effect.
- Tetracyclines and other drugs that raise intracranial pressure
- Avoided because they add to the risk of pseudotumour cerebri.
- Antifibrinolytics (tranexamic acid, aminocaproic acid)
- Avoided because of the risk of thrombosis.
- Vitamin A supplements
- Avoided; they add to retinoid toxicity.
What is monitored
- Daily weight, temperature, breathing and oxygen saturation in the first weeks (differentiation syndrome)
- White cell count
- Coagulation tests
- Fasting triglycerides and cholesterol
- Liver tests
- Pregnancy test before starting
Administration and safety
- Oral capsules, swallowed whole; the oral leukaemia capsules are a different product from tretinoin creams and gels for acne.
- A negative pregnancy test and two effective contraceptive methods are required for women who can become pregnant.
- It may be started on a morphological diagnosis of APL while genetic confirmation is pending.
- At the first signs of differentiation syndrome, corticosteroids are started immediately as ordered.
Pregnancy and breastfeeding
Avoid in pregnancy. A potent teratogen (boxed warning): pregnancy must be excluded before and prevented during treatment and for a month after; breastfeeding is not advised.
Nursing care
- Weigh daily and check temperature, breathing and saturation; report fever, breathlessness or weight gain at once.
- Look for bleeding and follow coagulation results (APL causes coagulopathy).
- Ask about headache, vomiting or blurred vision (raised intracranial pressure).
- Teaching: two forms of contraception, no vitamin A supplements, and moisturisers for dry skin and lips.
Pharmacokinetics
- Absorption
- Oral capsules; about half of the dose is absorbed.
- Distribution
- Highly bound to albumin.
- Metabolism
- Liver CYP enzymes (CYP3A4, CYP2C8) and glucuronidation; it induces its own metabolism, so levels fall within a week.
- Elimination
- Metabolites mainly in the urine, the rest in the faeces.
- Half-life
- Short: about half an hour to two hours.
Test yourself
Think of the answer, then tap the question to see it.
Which fusion protein does tretinoin act on in APL?
PML-RARα, produced by the t(15;17) translocation.
Five days into tretinoin, a patient has fever, dyspnoea, weight gain and lung infiltrates. What is it, and what is done?
Differentiation syndrome; high-dose corticosteroids are started immediately with haemodynamic monitoring.
Why is tranexamic acid avoided with tretinoin?
Because the combination increases the risk of thrombosis.
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - TRETINOIN capsule (DailyMed (U.S. National Library of Medicine), 2026); Tretinoin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2016); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.