COPIKTRA
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COPIKTRA (COPIKTRA).
| Breastfeeding | No data on duvelisib presence in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions (e.g., immunosuppression, neutropenia), advise women not to breastfeed during treatment and for at least 1 month after last dose. M/P ratio unknown. |
| 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. |
■ 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 |
["Concurrent use with strong CYP3A inhibitors due to increased toxicity risk"]
| 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"] |
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| 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. |