COPIKTRA
Clinical safety rating
cautionComprehensive clinical and safety monograph for COPIKTRA (COPIKTRA).
Selective phosphoinositide 3-kinase (PI3K) delta and gamma inhibitor. Blocks PI3K signaling, reducing proliferation and survival of malignant B cells and T cells, and inhibits chemotaxis and adhesion of these cells.
| Metabolism | Primarily metabolized by CYP3A4; also involves CYP3A5 and UDP-glucuronosyltransferases (UGTs). |
| Excretion | Primarily via fecal excretion (approximately 70% of total dose) as unchanged drug and metabolites, with renal excretion accounting for <15% of the dose. |
| Half-life | Terminal elimination half-life is approximately 7–10 hours in patients with relapsed or refractory CLL/SLL. Steady-state is achieved within 3–5 days of twice-daily dosing. |
| Protein binding | ~84% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Mean apparent volume of distribution (Vz/F) is approximately 100–150 L (or ~1.4–2.1 L/kg based on typical body weight), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 22% following a 25 mg capsule under fasting conditions. Absorption is increased with high-fat meals; therefore, it should be taken on an empty stomach. |
| Onset of Action | Clinical response (e.g., reduction in lymphadenopathy) may be observed within 2–4 weeks of initiating oral therapy, though maximal response may require several months. |
| Duration of Action | Duration of effect is continuous with daily dosing. Drug levels decline after last dose with a half-life of ~7–10 hours, but pharmacodynamic effects on target engagement (PI3Kδ) may persist for several days. |
| Molecular Weight | 489.57 |
25 mg orally twice daily
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild (Child-Pugh class A) or moderate (Child-Pugh class B), reduce dose to 25 mg once daily. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment recommended for elderly patients, but monitor for adverse effects due to potential age-related renal or hepatic impairment. |
| 1st trimester | Contraindicated due to risk of embryo-fetal toxicity based on animal studies showing teratogenicity and developmental delay. |
| 2nd trimester | Contraindicated; may cause fetal harm due to ongoing organogenesis and risk of low birth weight and skeletal abnormalities. |
| 3rd trimester | Contraindicated; risk of fetal harm continues, including potential for neonatal myelosuppression and immune suppression. |
Clinical note
Comprehensive clinical and safety monograph for COPIKTRA (COPIKTRA).
| Placental transfer | Expected to cross placenta based on molecular weight and animal studies; distribution to fetal tissues confirmed in rats. |
| Breastfeeding | No human data; drug excreted in animal milk. Potential for serious adverse reactions in nursing infants, including immunosuppression and increased infection risk. Advise against breastfeeding during treatment and for at least 10 days after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | COPIKTRA (duvelisib) is contraindicated in pregnancy. Based on its mechanism of action as a PI3K inhibitor and animal studies, it can cause fetal harm. In animal reproduction studies, duvelisib was embryotoxic and fetotoxic at maternal exposures below the recommended human dose. There are no adequate human data. Risks include embryo-fetal mortality, structural abnormalities, and growth impairment across all trimesters. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential prior to therapy and periodically during treatment due to risk of neutropenia. Monitor liver function tests, renal function, and serum electrolytes. For pregnant patients inadvertently exposed, perform fetal ultrasound to assess for anomalies. No specific maternal-fetal monitoring protocols established. |
| Fertility Effects | Based on animal studies, duvelisib may impair female fertility. In rats, ovarian effects (reduced corpora lutea, antral follicles) were observed at exposures below clinical levels. Effects on male fertility have not been adequately studied, but testicular degeneration was noted in animal studies. Human fertility data are lacking. |
■ FDA Black Box Warning
WARNING: FATAL AND SERIOUS TOXICITIES: Fatal and serious toxicities including infections, diarrhea or colitis, cutaneous reactions, and pneumonitis have occurred with COPIKTRA.
| Serious Effects |
Hypersensitivity to duvelisib or any excipientConcurrent use with strong CYP3A4 inducersPregnancySevere hepatic impairment (Child-Pugh class C)
| Precautions | Fatal and serious infections, Fatal and serious diarrhea or colitis, Fatal and serious cutaneous reactions, Fatal and serious pneumonitis, Neutropenia, Hepatotoxicity, Embryo-fetal toxicity |
| Food/Dietary | Avoid grapefruit and grapefruit juice; may increase dupilumab exposure. Take with or without food. |
| Clinical Pearls | Monitor for hepatotoxicity with baseline and periodic liver function tests; avoid live vaccines; consider dose reduction in patients with moderate hepatic impairment (Child-Pugh B); watch for infections due to neutropenia; contraindicated in severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Avoid grapefruit and grapefruit juice during treatment. · Report any signs of infection (fever, chills, cough) or jaundice (yellowing skin/eyes) immediately. · Use effective contraception during treatment and for at least 1 month after the last dose. · Do not receive live vaccines during or shortly after treatment. |
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