Drug Class Description
Retinoids.
Generic Name
Tretinoin
Drug Description
VESANOID®10 mg soft capsules
Presentation
Capsule, softBi-coloured orange-yellow / reddish-brown capsules.
Indications
VESANOID (tretinoin) is indicated for induction of remission in acute promyelocytic leukaemia (APL; FAB classification AML-M3).This treatment is intended for previously untreated patients as well as patients who relapse after a standard chemotherapy (anthracycline and cytosine arabinoside or equivalent therapies) or patients who are refractory to chemotherapy.The association of tretinoin with chemotherapy increases the duration of survival and reduces the risk of relapse compared to chemotherapy alone.
Adult Dosage
A total daily dose of 45 mg/m2 body surface divided in two equal doses is recommended for oral administration. This is approximately 8 capsules per adult dose.
Capsules should be swallowed together with water. Capsules should not be chewed. It is recommended to take the capsules with a meal or shortly thereafter.
There is limited safety and efficacy information on the use of tretinoin in children.
Pediatric patients can be treated with 45 mg/m2 unless severe toxicity becomes apparent. Dose reduction should be particularly considered for children with intractable headache.
Treatment should be continued until complete remission has been achieved or up to a maximum of 90 days.
Due to limited information on patients with hepatic and/or renal insufficiency, the dose will be decreased to 25 mg/m2 as a precautionary measure.
Full-dose anthracycline-based chemotherapy should be added to the tretinoin regimen as follows:
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When the leukocyte count at start of therapy is greater than 5 x 10 9/L, chemotherapy should be started together with tretinoin on day one.
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When the leukocyte count at start of therapy is less than 5 x 10 9/L but rapidly increases during tretinoin therapy, chemotherapy should be immediately added to the tretinoin regimen if the leukocyte count reaches greater than 6 x 10 9/L by day five, or greater than 10 x 109/L by day ten, or greater than 15 x 109/L by day 28.
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All other patients should receive chemotherapy immediately after complete remission is attained.
If chemotherapy is added to tretinoin because of hyperleukocytosis, it is not necessary to modify the dose of tretinoin.
After completion of tretinoin therapy and the first chemotherapy course, consolidation anthracycline-based chemotherapy should be given, for example, a further two courses at 4 to 6 week intervals.
In some patients the plasma levels of tretinoin may fall significantly in spite of continued administration
Contra Indications
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Known allergy to tretinoin, retinoids or to any of the excipients.
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Pregnancy
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Lactation
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Tetracyclines
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Vitamin A
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Vesanoid contains soya-bean oil, therefore Vesanoid is contraindicated in patients allergic to soya or peanuts.
Special Precautions
Tretinoin should be administered to patients with acute promyelocytic leukaemia only under the strict supervision of a physician who is experienced in the treatment of hematological / oncological diseases.
Supportive care appropriate for patients with acute promyelocytic leukaemia, for example prophylaxis for bleeding and prompt therapy for infection, should be maintained during therapy with tretinoin. The patient's hematologic profile, coagulation profile, liver function test results, and triglyceride and cholesterol levels should be monitored frequently.
During clinical trials hyperleukocytosis has been frequently observed (in 75% of the cases), sometimes associated with the “Retinoic Acid Syndrome”. Retinoic acid syndrome has been reported in many acute promyelocytic leukaemia patients (up to 25% in some centers) treated with tretinoin.
Retinoic acid syndrome is characterized by fever, dyspnoea, acute respiratory distress, pulmonary infiltrates, pleural and pericardial effusions, hypotension, oedema, weight gain, hepatic, renal and multi-organ failure.
Retinoic acid syndrome is frequently associated with hyperleukocytosis and may be fatal.
The incidence of the retinoic acid syndrome is diminished when full dose chemotherapy is added to the tretinoin regimen based on the white blood cell count. The current therapeutic treatment recommendations and method of administration are detailed in section 4.2.
Immediate treatment with dexamethasone (10 mg every 12 hours for up to maximum 3 days or until resolution of the symptoms) should be given, if the patient presents any symptom(s) or sign(s) of this syndrome.
In cases of moderate and severe retinoic acid syndrome, temporary interruption of Vesanoid therapy should be considered.
Vesanoid may cause pseudotumour cerebri. This condition should be treated according to standard medical practice. Temporary discontinuation of Vesanoid should be considered in patients not responding to treatment.
Sweet's syndrome or acute febrile neutrophilic dermatitis responded dramatically to corticosteroid treatment.
There is a risk of thrombosis (both venous and arterial) which may involve any organ system, during the first month of treatment. Therefore, caution should be exercised when treating patients with the combination of Vesanoid and anti-fibrinolytic agents, such as tranexamic acid, aminocaproic acid or aprotinin.
Because hypercalcaemia may occur during therapy, serum calcium levels should be monitored.
Micro-dosed progesterone preparations (”minipill”) are an inadequate method of contraception during treatment with tretinoin.
Vesanoid contains sorbitol, therefore patients with rare hereditary problems of fructose intolerance should not take Vesanoid.
Interactions
Tetracyclines
