IDELALISIB
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IDELALISIB (IDELALISIB).
Idelalisib is a phosphoinositide 3-kinase (PI3K) delta isoform inhibitor. It inhibits the delta isoform of PI3K, which is selectively expressed in B-cells and plays a role in B-cell activation, proliferation, and survival. By blocking PI3K delta signaling, idelalisib reduces cell proliferation and induces apoptosis in malignant B-cells.
| Metabolism | Idelalisib is primarily metabolized by aldehyde oxidase (AO) and to a lesser extent by CYP3A4. It undergoes oxidation to form a major metabolite (GS-563117) which is pharmacologically inactive. |
| Excretion | Primary fecal (78%) with minor renal (14% unchanged) and biliary contribution. |
| Half-life | Terminal elimination half-life approximately 8.2 hours; supports twice-daily dosing. |
| Protein binding | 84% bound to plasma proteins, primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 10 L/kg; extensive tissue distribution, with high penetration into lymphoid tissues. |
| Bioavailability | Oral: approximately 41% (under fasting conditions); increased with high-fat meal. |
| Onset of Action | Oral: Peak plasma concentration at 1.5–2.5 hours; clinical effect (e.g., lymph node reduction) observed within 1–2 weeks. |
| Duration of Action | Duration of receptor occupancy lasts approximately 24 hours; continuous twice-daily dosing required for sustained effect. |
150 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Not recommended if GFR <15 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 100 mg orally twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor for toxicity due to age-related physiological changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IDELALISIB (IDELALISIB).
| Breastfeeding | It is unknown if idelalisib is excreted in human milk. Due to potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least 1 month after the last dose. M/P ratio not available. |
| Teratogenic Risk | Idelalisib is contraindicated in pregnancy. Based on its mechanism of action (PI3Kδ inhibitor) and animal studies, it can cause fetal harm. No adequate human data exist, but teratogenic effects are expected across all trimesters, including embryotoxicity, fetotoxicity, and malformations. |
■ FDA Black Box Warning
WARNING: FATAL AND/OR SERIOUS TOXICITIES: Hepatotoxicity, severe diarrhea or colitis, pneumonitis, and intestinal perforation. Fatal and/or serious hepatotoxicity occurred in clinical trials. Monitor hepatic function. Fatal and/or serious diarrhea or colitis occurred. Monitor for diarrhea. Fatal and/or serious pneumonitis occurred. Monitor for pulmonary symptoms. Fatal and/or serious intestinal perforation occurred. Discontinue for intestinal perforation.
| Serious Effects |
["History of severe hypersensitivity reactions to idelalisib or any of its excipients"]
| Precautions | ["Hepatotoxicity: Monitor ALT, AST, and bilirubin levels. Interrupt or discontinue therapy based on severity.","Severe diarrhea or colitis: Monitor for diarrhea. Interrupt or discontinue therapy based on severity.","Pneumonitis: Monitor for pulmonary symptoms (cough, dyspnea, hypoxia). Discontinue for pneumonitis.","Intestinal perforation: Discontinue if suspected.","Infections: Fatal and serious infections, including opportunistic infections, may occur. Monitor for signs/symptoms.","Cutaneous reactions: Severe skin reactions, including exfoliative dermatitis, have been reported.","Neutropenia: Monitor neutrophil counts regularly.","Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential to use effective contraception."] |
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| Fetal Monitoring |
| If unintentional exposure occurs during pregnancy, monitor fetal development with ultrasound. Monitor liver function tests, serum lipase, and complete blood counts due to risk of hepatotoxicity, pancreatitis, and diarrhea/colitis. Monitor for infections. |
| Fertility Effects | Based on animal studies, idelalisib may impair male and female fertility. In male rats, decreased sperm counts and motility were observed. Effects on human fertility are unknown but potential exists. |