Vesanoid Dosage/Direction for Use

Dosage: For all therapy phases, a total daily dose of 45 mg/m² body surface divided into two equal doses is recommended for oral administration to adult and elderly APL patients. This is approximately 8 capsules per patient per day (one capsule contains 10 mg tretinoin).
Paediatric population: There is limited safety and efficacy information on the use of tretinoin in children. For children the same treatment regimen as for adults is applicable. The optimal paediatric dose of tretinoin has not yet been established. In an attempt to reduce tretinoin related toxicity, the daily dose administered in children can be reduced to 25 mg/m². Dose reduction should be particularly considered for children with toxicity symptoms, such as intractable headache.
High risk patients: For patients at high risk of disease relapse according to Sanz score (see Indications), 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: Patients with hyperleukocytosis (see Precautions) can receive additional chemotherapy at the very onset of induction treatment.
Patients with hepatic and/or renal impairment: Due to the limited information on patients with hepatic and/or renal insufficiency, the dose will be decreased to 25 mg/m² as a precautionary measure.
Dose delay, modification and re-initiation: In cases of severe differentiation syndrome (DS, see Precautions), temporary interruption of tretinoin therapy should be considered. Treatment with tretinoin may need to be withheld during the initial acute symptomatic period, but may be resumed when symptoms resolve. If intracranial hypertension/pseudotumour cerebri occur, a reduction of tretinoin dose is recommended.
Method of administration: The capsules should be swallowed whole with water. They should not be chewed. It is recommended to take the capsules with a meal or shortly thereafter.
Induction therapy should be continued until complete remission has been achieved or up to a maximum of 90 days.
After completion of induction, consolidation therapy should be initiated with a tretinoin/ arsenic trioxide combination or with a tretinoin/ anthracycline-based chemotherapy regimen. As for induction therapy, the same tretinoin dose of 45 mg/m² body surface divided in two equal doses is recommended for oral administration during consolidation. Several cycles of consolidation therapy with tretinoin should be performed. Current guidelines recommend that tretinoin-free intervals are included after remission and during consolidation cycles.
If maintenance therapy is performed, tretinoin should be used at the same dose as for induction/consolidation therapy. As for consolidation therapy, in case of treatment with tretinoin for maintenance therapy treatment regimen should include drug-free intervals ("pulsed therapy"). If there has been a remission with tretinoin alone, it is not necessary to modify doses of tretinoin if tretinoin is used with chemotherapy.