Retinoid (ATRA) Pregnancy: Tretinoin is teratogenic — there is a high risk of severe malformation of the foetus, particularly when given during the first trimester, and it must not be used during pregnancy or in women of childbearing potential not using contraception unless the clinical condition of the woman (severity of the condition, urgency of treatment) requires it. Every woman of childbearing potential must use a reliable contraception method without interruption during and for one month after discontinuation of treatment, and pregnancy tests must be performed at monthly intervals during therapy. Breast-feeding must be discontinued if therapy is initiated.

Tretinoin (Specialist drug)

Brand names: Vesanoid

Tretinoin (all-trans retinoic acid) is an oral retinoid used under specialist supervision to induce remission in acute promyelocytic leukaemia.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 45 mg/m2 body surface per day, divided into two equal doses (approximately 8 capsules per patient per day; one capsule contains 10 mg tretinoin) — for adult and elderly patients with acute promyelocytic leukaemia (APL)

Route: Oral — capsules should be swallowed whole with water and not chewed; it is recommended to take them with a meal or shortly thereafter

Frequency: Two equal divided doses daily, for all therapy phases

Induction therapy should be continued until complete remission has been achieved or up to a maximum of 90 days. After induction, consolidation therapy should be started with a tretinoin/arsenic trioxide combination or a tretinoin/anthracycline-based chemotherapy regimen; the recommended tretinoin dose during consolidation is the same as for induction (45 mg/m2/day in two equal divided doses), and several consolidation cycles should be given with tretinoin-free intervals as recommended by current guidelines. If maintenance therapy is given, tretinoin is used at the same dose as for induction/consolidation, with tretinoin-free intervals ('pulsed therapy'). National/local practice guidelines or protocols should be considered as clinical practice varies. High-risk patients (high risk of relapse by Sanz score): a treatment option is the triple combination of tretinoin, arsenic trioxide and chemotherapy (anthracyclines) for induction, followed by consolidation with tretinoin and arsenic trioxide. Patients with hyperleukocytosis can receive additional chemotherapy at the very onset of induction treatment. Dose delay/modification: in cases of severe differentiation syndrome, temporary interruption of tretinoin should be considered — treatment may need to be withheld during the initial acute symptomatic period and may be resumed when symptoms resolve; if intracranial hypertension/pseudotumour cerebri occurs, a reduction of the tretinoin dose is recommended. Paediatric population: there is limited safety and efficacy information on the use of tretinoin in children; the same treatment regimen as for adults is applicable and the optimal paediatric dose has not yet been established. In an attempt to reduce tretinoin-related toxicity, the daily dose administered to children can be reduced to 25 mg/m2 — dose reduction should be particularly considered for children with toxicity symptoms such as intractable headache. The paediatric dose is body-surface-area based, not per kg, so no per-kg paediatric dose is recorded.

Dose adjustments

Renal

Patients with hepatic and/or renal impairment: due to limited information, the dose will be decreased to 25 mg/m2 as a precautionary measure.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to tretinoin, other retinoids, soya, peanut or to any of the excipients
Breast-feeding (tretinoin is teratogenic)
Combination with vitamin A, tetracyclines or retinoids

Side effects

Very common signs and symptoms of hypervitaminosis A syndrome — headache, increased intracranial pressure, pseudotumour cerebri, dizziness, paraesthesia, dry mouth, cheilitis, erythema, rash, pruritus, alopecia, hyperhidrosis and bone pain
Differentiation syndrome (formerly retinoic acid syndrome) — may be fatal; characterised by fever, dyspnoea, acute respiratory distress, pulmonary infiltrates and pleural effusions
Very common gastrointestinal effects: nausea, vomiting, abdominal pain, diarrhoea, constipation, pancreatitis and decreased appetite
Very common cardiovascular and respiratory effects: arrhythmia, flushing, respiratory failure, nasal dryness and asthma; arterial and venous thrombosis, myocardial infarction, myocarditis and pericarditis reported post-marketing
Very common psychiatric and laboratory changes: confusional state, anxiety, depression, insomnia; increased blood triglycerides, cholesterol and creatinine, and increased transaminases; also visual disturbances, conjunctival disorders, hearing impairment, chest pain, chills and malaise

Interactions

Combination with vitamin A, tetracyclines or other retinoids is contraindicated (stated in SPC §4.3; the SPC §4.5 interaction section was not retrieved in the fetched bundle and must be checked in full by the reviewing clinician)

Clinical monograph

How it works

It promotes terminal differentiation of the abnormal promyelocytes driven by the PML-RARA fusion, allowing leukaemic cells to mature rather than proliferate.

Prescribing in practice

Differentiation syndrome (retinoic acid syndrome) with fever, fluid overload and respiratory distress can be life-threatening and needs prompt recognition and corticosteroid treatment.
It is highly teratogenic, so pregnancy must be excluded and effective contraception ensured.
Treatment is given by haematology specialists, commonly alongside arsenic trioxide or chemotherapy per the SPC.

Monitoring

Monitor full blood count, coagulation, liver function and for features of differentiation syndrome during induction.

Counselling the patient

Report breathlessness, fever, weight gain or swelling urgently as these may signal differentiation syndrome.
Pregnancy must be avoided; use reliable contraception as directed.
Headache, dry skin and lips are common and should be mentioned if troublesome.

Evidence & guidelines

Combined ATRA-based therapy is established by landmark APL trials (e.g. APL0406) and supported by haematology guidelines.

Reference: SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways