tretinoin: clinical use

Prescribing considerations

• Restrict use to specialist haematology or oncology supervision with supportive care for bleeding and infection.
• Genetic confirmation of APL is mandatory, although treatment may begin on morphological suspicion because of early haemorrhagic death risk.
• Act promptly on possible differentiation syndrome, hyperleukocytosis, intracranial hypertension, thrombosis, hepatotoxicity or psychiatric deterioration.
• Renal and hepatic impairment require specialist assessment; children have limited safety data and may be more susceptible to intracranial hypertension.

Contraindications and cautions

• Hypersensitivity to tretinoin, other retinoids or any excipient.
• Peanut or soya allergy because the capsule contains soya-bean oil.
• Breastfeeding.
• Concomitant vitamin A, tetracyclines or other retinoids.

Monitoring

• Haematological and coagulation profiles.
• Clinical features of differentiation syndrome and rising white-cell count.
• Liver function, triglycerides, cholesterol, creatinine and serum calcium.
• ECG and QTc with arsenic trioxide where additional risk factors exist.
• Headache, visual symptoms and other signs of intracranial hypertension.
• Mood or behavioural changes.
• Pregnancy status and contraceptive requirements where relevant.

Clinical pharmacology

Tretinoin is all-trans retinoic acid, an endogenous vitamin A metabolite. In APL it promotes degradation of PML–RARα and restores retinoid-receptor signalling, allowing promyelocytes to differentiate. Oral exposure varies considerably and metabolism involves CYP3A4 and CYP26A1.

Formulation and product differences

• The selected product is an oral soft capsule for APL and should not be confused with topical tretinoin preparations used for skin conditions.
• The capsule contains soya-bean oil, gelatin and a small amount of sorbitol.
• The capsule is essentially sodium-free and must be protected from moisture and light.

Capsule

Route: Oral

Strengths: 10 mg