Tretinoin Capsules are a retinoid-based targeted medication for the treatment of acute promyelocytic leukemia (APL). It exerts therapeutic effects by inducing the differentiation of leukemia cells and inhibiting their proliferation, but it also carries serious risks such as embryotoxicity and differentiation syndrome.

Precautions for Administration of Tretinoin Capsules

Contraindications and Baseline Assessment

Contraindicated Populations: It is contraindicated in patients allergic to tretinoin or other retinoids. Pregnant women are absolutely contraindicated (as it may cause fetal death or malformation).

Confirmation Before Administration: It is mandatory to confirm the presence of t(15,17) translocation or PML/RARα fusion gene in patients via cytogenetic or molecular testing; otherwise, its use is not recommended.

Pregnancy Screening: Women of childbearing age must undergo a pregnancy test with a sensitivity of ≥50mIU/mL within 1 week before administration, and medication can only be given if the result is negative.

Administration Specifications

Dosage and Treatment Course: The recommended dosage is 22.5mg/m², taken orally twice daily until complete remission is achieved. After remission, continue medication for no more than 30 days, with the total treatment course not exceeding 90 days.

Administration Method: The capsules should be swallowed whole with meals; they must not be chewed, dissolved, or opened. If vomiting occurs after administration, no supplementary dose is needed, and the next dose should be taken as scheduled.

Management of Missed Doses: If the interval until the next scheduled dose is more than 10 hours, the missed dose can be taken; otherwise, skip the missed dose.

Management of Special Populations

Patients of Childbearing Age: Female patients should use double contraceptive measures (e.g., hormonal contraception + barrier method) until 1 month after the last dose.

Male Patients: Effective contraceptive measures should be taken during treatment and within 1 week after discontinuing the medication.

Pediatric Patients: It can be used in children over 1 year old, but caution is required regarding the risk of increased intracranial pressure. The safety of use in children under 1 year old has not been established.

Lactating Women: Breastfeeding is prohibited during treatment and within 1 week after discontinuing the medication.

Risks of Drug Interactions

CYP3A Inhibitors/Inducers: Potent CYP3A inhibitors (e.g., ketoconazole) may increase the blood concentration of the drug and elevate toxicity, while potent CYP3A inducers (e.g., rifampicin) may reduce its efficacy. Concurrent use of these drugs should be avoided.

Vitamin A and Other Retinoids: Concurrent use may exacerbate tretinoin-related toxicity (e.g., dry skin, liver injury).

Antifibrinolytic Drugs (e.g., tranexamic acid): Concurrent use increases the risk of thrombosis and is strictly prohibited.

Monitoring During Administration of Tretinoin Capsules

Efficacy Monitoring

Hematological Indicators: Monitor white blood cell count weekly. Approximately 40% of patients may experience a rapid increase in white blood cell count (the risk is higher when the count exceeds 5×10⁹/L), and the combined use of cytoreductive chemotherapy should be considered based on clinical conditions.

Differentiation Syndrome: It occurs in 26% of patients, presenting with symptoms such as fever, dyspnea, weight gain, and hypotension. Once symptoms appear, dexamethasone (10mg every 12 hours) should be administered intravenously immediately, and suspension of tretinoin may be necessary if required.

Lipid and Liver Function Monitoring

Lipids: 60% of patients develop hypercholesterolemia/hypertriglyceridemia. Fasting lipid levels should be tested regularly at baseline and during treatment.

Liver Function: 50% to 60% of patients experience elevated liver enzymes. Alanine transaminase (ALT) and aspartate transaminase (AST) should be monitored; if the levels exceed 5 times the upper limit of normal, consideration should be given to discontinuing the medication.

Special Monitoring of Organ Function

Intracranial Pressure: Pediatric patients, in particular, require close monitoring for symptoms such as headache, blurred vision, and vomiting. If intracranial hypertension is suspected, a neurological evaluation should be conducted, and suspected interacting drugs (e.g., tetracyclines) should be discontinued.

Thrombotic Events: Venous/arterial thrombosis (e.g., stroke, myocardial infarction) is likely to occur in the first month of treatment. Manifestations such as limb swelling and chest pain should be closely observed.

Renal Function and Electrolytes: Differentiation syndrome may lead to acute renal failure, so urine output and creatinine levels should be monitored.