ZYDELIG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYDELIG (ZYDELIG).
Idelalisib is a selective inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), blocking the PI3K/AKT signaling pathway, leading to reduced proliferation, survival, and migration of malignant B cells.
| Metabolism | Primarily metabolized by aldehyde oxidase (AO) and CYP3A4, with minor contributions from UGT1A4. |
| Excretion | Primarily hepatic metabolism, with 44% of dose excreted in feces (as metabolites) and 22% in urine (unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is 6.5 hours (range 4-10 hours) after oral administration, supporting twice-daily dosing. |
| Protein binding | 84% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean volume of distribution is 113 L (approximately 1.4 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is 40% (range 30-50%) due to first-pass metabolism. |
| Onset of Action | Time to peak plasma concentration (Tmax) is approximately 1.5 hours after oral administration; clinical effect onset correlates with plasma levels. |
| Duration of Action | Duration of PI3Kδ inhibition is approximately 12 hours, consistent with twice-daily dosing regimen. |
150 mg orally twice daily, taken with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Reduce dose to 100 mg twice daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Safety and efficacy not established for patients <18 years. |
| Geriatric use | No specific dose adjustment recommended, but monitor for age-related renal and hepatic function changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYDELIG (ZYDELIG).
| Breastfeeding | No human data on presence in breast milk; risk of serious adverse reactions in breastfed infants (immunosuppression, neutropenia). M/P ratio not determined. Advise not to breastfeed during treatment and for 1 week after last dose. |
| Teratogenic Risk | Pregnancy Category D. First trimester: Risk of fetal malformations including neural tube defects and craniofacial anomalies based on animal studies showing embryo-fetal toxicity and teratogenicity. Second and third trimesters: Risk of fetal hematologic toxicity (leukopenia, neutropenia) and potential growth restriction. Counsel women of childbearing age to use effective contraception during treatment and for 1 month after last dose. |
■ FDA Black Box Warning
WARNING: FATAL AND SERIOUS TOXICITIES: Hepatic, severe diarrhea/colitis, pneumonitis, and intestinal perforation. Fatal and/or serious hepatotoxicity occurred in 18% of patients. Fatal and/or serious diarrhea or colitis occurred in 14%. Fatal and/or serious pneumonitis occurred in 4%. Fatal and/or serious intestinal perforation occurred in <1%.
| Serious Effects |
["History of severe hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome) to idelalisib or any excipient"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests","Severe diarrhea/colitis: Manage with supportive care and corticosteroids","Pneumonitis: Interrupt therapy and evaluate","Intestinal perforation: Discontinue if suspected","Infections: Monitor for opportunistic infections, including CMV","Neutropenia: Monitor blood counts","Embryofetal toxicity: Can cause fetal harm","Vaccinations: Avoid live vaccines during treatment"] |
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| Fetal Monitoring | Monitor complete blood count (CBC) including absolute neutrophil count (ANC) every 2 weeks for first 3 months, then monthly. Assess for signs of infection or bleeding. Perform pregnancy test before initiation and monthly during treatment. Monitor liver function tests (ALT, AST, bilirubin) and renal function (serum creatinine). Monitor fetal growth and amniotic fluid volume via ultrasound if pregnancy occurs during treatment. |
| Fertility Effects | Based on animal studies, may impair female fertility; effects on male fertility unknown. In humans, oligospermia, asthenospermia, or azoospermia reported in males; reversible upon discontinuation. Females may experience menstrual irregularities, amenorrhea, or premature ovarian failure. |