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. |
| Molecular Weight | 415.3 |
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 | Avoid. Zydelig (idelalisib) is a PI3K inhibitor with teratogenic potential based on animal studies; risk of fetal harm. |
| 2nd trimester | Avoid. No adequate human data; based on animal studies, may cause fetal harm. |
| 3rd trimester | Avoid. Potential risk of fetal harm; no human data. |
Clinical note
Comprehensive clinical and safety monograph for ZYDELIG (ZYDELIG).
| Placental transfer | Expected to cross placenta due to low molecular weight; no specific human data. |
| Breastfeeding | No information available on presence in human milk; advise against breastfeeding due to potential serious adverse effects in infant. |
| Lactation Rating |
■ 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 |
Hypersensitivity to idelalisibKnown severe hepatic impairment (Child-Pugh class C)
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice (CYP3A4 inhibition increases idelalisib exposure). Take with food to reduce nausea and diarrhea. |
Loading safety data…
| L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | Monitor for hepatotoxicity (ALT/AST elevations), severe cutaneous reactions (Stevens-Johnson syndrome), and pneumonitis. Requires hepatic function monitoring every 2 weeks for first 2 months, then monthly. Contraindicated with CYP3A4 inducers or strong inhibitors due to metabolism via CYP3A4. Dose reduction needed for moderate hepatic impairment (Child-Pugh B). |
| Patient Advice | Take with food to reduce gastrointestinal side effects. · Avoid grapefruit and grapefruit juice during treatment. · Report any signs of liver problems (jaundice, dark urine, abdominal pain) or skin reactions (rash, blisters) immediately. · Use effective contraception during and for at least 1 month after treatment. · Do not stop or change dose without consulting your healthcare provider. |