Eflornithine

IWILFIN (eflornithine) is indicated to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. IWILFIN is an ornithine decarboxylase inhibitor indicated to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy.

Eflornithine is an irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines and a transcriptional target of MYCN. Polyamines are involved in differentiation and proliferation of mammalian cells and are important for neoplastic transformation. Inhibition of polyamine synthesis by eflornithine restored the balance of the LIN28/Let-7 metabolic pathway, which is involved in regulation of cancer stem cells and glycolytic metabolism, by decreasing expression of the oncogenic drivers MYCN and LIN28B in MYCN -amplified neuroblastoma. In vitro, eflornithine induced senescence and suppressed neurosphere formation in MYCN -amplified and MYCN non-amplified neuroblastoma cells, indicating a cytostatic effect.

Prior to initiation of IWILFIN, perform baseline audiogram, complete blood count, and liver function tests. Recommended dosage of IWILFIN is based on body surface area. IWILFIN is taken orally twice daily with or without food until disease progression, unacceptable toxicity, or for a maximum of two years. IWILFIN tablets may be swallowed whole, chewed, or crushed and mixed with soft food or liquid.

None. None

Myelosuppression: Monitor blood counts before and during treatment with IWILFIN. Withhold, reduce dose, or permanently discontinue based on severity. Hepatotoxicity: Monitor liver function tests before and during treatment with IWILFIN. Hearing Loss: Monitor hearing before and during treatment with IWILFIN. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression Hepatotoxicity Hearing Loss Most common adverse reactions (incidence ≥5%) are hearing loss, otitis media, pyrexia, pneumonia, and diarrhea. Most common Grade 3 or 4 laboratory abnormalities (incidence ≥2%) are increased ALT, increased AST, decreased neutrophil count, and decreased hemoglobin.

Store at room temperature, 20°C to 25°C (68°F to77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).