IWILFIN
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IWILFIN (IWILFIN).
| Breastfeeding | IWILFIN is excreted in human breast milk with a milk-to-plasma (M/P) ratio of 0.85. Potential for serious adverse reactions in nursing infants, including CNS depression and growth impairment. Decision to discontinue breastfeeding or drug based on importance of drug to mother. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Pregnancy (can cause fetal harm based on animal studies). Concomitant use with strong CYP3A4 inducers or inhibitors (may alter IWILFIN exposure). Hypersensitivity to IWILFIN or any of its excipients.
| 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. |
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| 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. |