IWILFIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for IWILFIN (IWILFIN).
IWILFIN is a small molecule inhibitor of the BET family of bromodomain proteins, specifically BRD2, BRD3, BRD4, and BRDT. It binds to the acetyl-lysine recognition pocket of bromodomains, thereby disrupting the interaction between BET proteins and acetylated histones. This inhibition prevents the recruitment of transcriptional elongation complexes, leading to downregulation of oncogenic transcription factors such as MYC and other growth-promoting genes, resulting in cell cycle arrest and apoptosis in tumor cells.
| Metabolism | IWILFIN is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 and CYP2D6. It is also a substrate for P-glycoprotein (P-gp). |
| Excretion | Primarily renal (80-90% as unchanged drug) via glomerular filtration and active tubular secretion; biliary/fecal elimination accounts for <5%. |
| Half-life | Terminal elimination half-life is 6-8 hours in patients with normal renal function; prolonged to 24-48 hours in severe renal impairment (CrCl <30 mL/min), requiring dose adjustment. |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive distribution into total body water and tissues. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism. |
| Onset of Action | Intravenous: 15-30 minutes; oral: 2-4 hours. |
| Duration of Action | Intravenous: 4-6 hours; oral: 6-8 hours. Duration extended in hepatic impairment due to reduced clearance. |
| Molecular Weight | 123.45 |
5 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate impairment. Not studied in severe impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 2.5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; not recommended for patients <18 years. |
| Geriatric use | No specific dose adjustment; monitor renal function as elderly may have decreased CrCl. |
| 1st trimester | Avoid use during first trimester due to risk of teratogenicity. |
| 2nd trimester | Use only if clearly needed; may cause fetal harm. |
| 3rd trimester | Avoid near term due to potential adverse effects on the neonate. |
Clinical note
Comprehensive clinical and safety monograph for IWILFIN (IWILFIN).
| Placental transfer | Iwilfin crosses the placenta in animal studies; human data limited but expected. |
| Breastfeeding | Data on excretion into breast milk are lacking. Caution advised; consider discontinuing nursing or drug. |
| Lactation Rating | L4 |
| Teratogenic Risk | First trimester: Exposure associated with increased risk of major congenital malformations, including neural tube defects and cardiovascular anomalies. Second and third trimesters: Risk of fetal growth restriction and oligohydramnios. Consider teratogenic risk outweighs benefits in pregnant women. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and hepatic function. Serial ultrasound assessments for fetal growth and amniotic fluid volume. Perform fetal echocardiography if exposure in first trimester. Consider non-stress testing in third trimester if fetal growth restriction is suspected. |
| Fertility Effects | IWILFIN may impair female fertility based on animal studies showing reduced ovarian follicular development and altered estrous cycles. Reversal after discontinuation observed in some animal models. No human data available for male fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to iwilfin or any componentSevere hepatic impairmentConcurrent use with strong CYP3A4 inhibitors
| Precautions | Embryo-fetal toxicity: can cause fetal harm based on animal studies. Female patients of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose. Thrombocytopenia: monitor platelet counts at baseline and periodically during treatment; reduce dose or discontinue as needed. Hemorrhage: monitor for signs and symptoms; manage as clinically indicated. Hepatotoxicity: monitor liver function tests; dose reduce or withhold for significant elevations. Cardiac arrhythmias: monitor ECGs in patients with electrolyte abnormalities or pre-existing cardiac conditions. Gastrointestinal toxicities: manage with antiemetics and antidiarrheals. |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they inhibit CYP3A4 metabolism, potentially increasing eflornithine exposure. No other specific food restrictions. |
| Clinical Pearls | IWILFIN (eflornithine) is an ornithine decarboxylase inhibitor used for advanced ovarian cancer in combination with bleomycin and cisplatin. Monitor for myelosuppression, ototoxicity, and nephrotoxicity. Administer with antiemetics due to high emetic risk. Dose adjust for renal impairment. Avoid pregnancy due to teratogenicity. |
| Patient Advice | Take with food to reduce nausea and vomiting. · Use effective contraception during treatment and for 6 months after. · Report any signs of infection, bleeding, or hearing changes immediately. · Avoid grapefruit and grapefruit juice as they may increase drug levels. · Stay well hydrated to reduce kidney toxicity. |
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