What are the precautions for taking eflornithine tablets?

In the clinical study of eflornithine tablets (eflornithine) in the treatment of neuroblastoma, warnings and precautions such as bone marrow suppression , liver toxicity, hearing damage, embryo-fetal toxicity appeared. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Myelosuppression: In the pooled safety population, 4.2% of patients experienced grade 3 or 4 neutropenia. Febrile neutropenia occurred in 0.6% of patients. One patient developed bone marrow failure. Grade 3 or 4 thrombocytopenia occurred in 1.4% of patients. Grade 3 anemia occurred in 3.3% of patients. Monitor blood cell counts, including neutrophil count, platelet count, and hemoglobin level, before usingeflornithine tablets and periodically during treatment.

2. Hepatotoxicity: In the pooled safety population, 11% of patients experienced grade 3 or 4 events of elevated alanine aminotransferase (ALT). Grade 3 or 4 events of elevated aspartate aminotransferase (AST) occurred in 6% of patients. Grade 3 or 4 events of elevated bilirubin occurred in 0.3% of patients. ALT/AST elevations resulting in dose interruption or reduction occurred in 2.5% of patients. 0.6% of patients discontinued eflornithine tablets due to elevated ALT/AST.

Perform liver function tests (ALT, AST, and total bilirubin) monthly for six months before starting treatment with eflornithine tablets, then every 3 months or as clinically indicated, and more frequently in patients with elevated transaminases or bilirubin.

3. Hearing loss: In the pooled safety population, 81% of patients had abnormal baseline audiograms. New or worsening hearing loss occurred in 13% of patients treated with eflornithine tablets; hearing loss worsened from baseline to grade 3 or 4 in 12% of patients. One patient developed tinnitus. Hearing loss occurred in 4% of patients, resulting in dose interruption or reduction. Seven percent of patients developed new or worsening hearing loss and required the return of hearing aids. 1.4% of patients discontinued eflornithine tablets due to hearing loss.

Of all patients who developed new or worsening hearing loss during treatment with eflornithine tablets, hearing loss returned to baseline in 9% of patients. Of the 18 patients who experienced new or worsening hearing loss and had a dose adjustment, 67% improved or returned to baseline. Before starting treatment, obtain an audiogram every 6 months, or as clinically indicated, to monitor for potential hearing loss.

4. Embryonic-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, eflornithine tablets can cause fetal damage when administered to pregnant women. In animal reproduction studies, oral administration of eflornithine to pregnant rats and rabbits during organogenesis resulted in embryonic lethality at doses equivalent to recommended human doses.

Inform pregnant women and women of reproductive potential of the potential risks to the fetus. It is recommended that females of reproductive potential use effective contraception during treatment with eflornithine tablets and within 1 week after the last dose. It is recommended that men with female partners of reproductive potential use effective contraception during treatment with eflornithine tablets and for 1 week after the last dose.

Reference materials:https://www.drugs.com/mtm/eflornithine.html