Extemporaneous compounding and administration of tretinoin slurry for acute promyelocytic leukemia

Abstract

Introduction Acute promyelocytic leukemia (APL) is a potentially curable malignancy with 4-year overall survival rates >90%. Early complications from the disease or its treatment may result in a loss of oral access and require alternative administration of medications. Tretinoin has been the backbone of APL therapy since the late 1990s and is only available as a liquid filled capsule. Case report Two patients with high-risk APL were unable to safely swallow tretinoin capsules due to complications of their disease. Management & outcome We prepared a tretinoin slurry using tretinoin 10 mg capsules, sterile water, and mineral oil at a ratio of 1 capsule to 2.75 mL sterile water to 1.25 mL mineral oil. This was successfully administered to both patients and no doses of tretinoin slurry were missed by either patient. In the patient who has long-term follow up available, a complete remission was achieved. Discussion Due to tretinoin’s known teratogenicity, this capsule should not be crushed, cut, or open, which limits its use in patients without oral access. Alternative routes of administration, such as via a nasogastric tube or sublingually, have not been safe and effective. By preparing a tretinoin slurry in our hazardous extemporaneous compounding area, we were able to safely and effectively prepare a tretinoin slurry that was successfully administered to two patients. This alternative preparation did not alter long-term outcomes and represents a viable option for patients who do not have oral access.

Predictors of very early death in acute promyelocytic leukemia: a retrospective real-world cohort study

“…In these scenarios, ATRA could be given via a nasogastric tube placed with precaution, but the size of the capsules and the inability to crush them can hamper their nasogastric administration. There are anecdotal reports on heating ATRA capsules in water until they melt [ 16 ], or dissolving ATRA with water and mineral oil into a slurry which can be more easily swallowed or administered via the tube [ 17 ]. The second scenario is that of patients under nil per os because of active gastric bleeding.…”

Monoterpenoids: An upcoming class of therapeutic agents for modulating cancer metastasis

“…The pharmaceutical compound known as alitretinoin, which is derived from vitamin A, is utilized in the treatment of Kaposi's sarcoma (Bodsworth et al, 2001). Tretinoin, a compound derived from vitamin A, is utilized for the therapeutic management of certain types of promyelocytic leukemia (Przybylski et al, 2021). Terpenoids are classified primarily based on the number of isoprene units (C5) present: hemi (C5), mono (C10), sesqui (C15), di (C20), sester (25), tri (C30), tetra (C40), and polyterpenoids (C5) n ; n > 8 (Kiyama, 2017).…”

Estudo de estabilidade físico-química de preparação extemporânea líquida à base de tretinoína para administração via sonda

“…Handling is recommended in a controlled environment to avoid occupational exposure, since the medication has teratogenic potential 8 . There are several preparation methods published in the literature, using the following vehicles: distilled water, milk, medium-chain triglycerides (MCT), water/mineral oil and oil, as well as the recommendation to aspirate the contents of the capsule [9][10][11] . Of particular interest is the preparation with water/mineral oil, since the water is added to break up the soft gel capsules and the mineral oil acts as a lipophilic vehicle for the ATRA, according to the method described by Okumura et al 10 .…”