Copiktra

COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) after at least two prior therapies.

Dosing

The recommended dose of COPIKTRA is 25 mg administered as oral capsules twice daily (BID) with or without food.  A cycle consists of 28 days.  The capsules should be swallowed whole. Advise patients not to open, break, or chew the capsules.

Advise patients that if a dose is missed by fewer than 6 hours, to take the missed dose right away and take the next dose as usual.  If a dose is missed by more than 6 hours, advise patients to wait and take the next dose at the usual time.

Recommended Prophylaxis

Provide prophylaxis for Pneumocystis jirovecii (PJP) during treatment with COPIKTRA.  Following completion of COPIKTRA treatment, continue PJP prophylaxis until the absolute CD4+ T cell count is greater than 200 cells/µL.

Withhold COPIKTRA in patients with suspected PJP of any grade, and discontinue if PJP is confirmed.

Consider prophylactic antivirals during COPIKTRA treatment to prevent cytomegalovirus (CMV) infection including CMV reactivation.

Dose Modifications for Adverse Reactions

Manage toxicities per Table 1 with dose reduction, treatment hold, or discontinuation of COPIKTRA.

Recommended dose modification levels for COPIKTRA are presented in Table 2.

Dosage Modification for Concomitant Use with CYP3A4 Inhibitors

Reduce COPIKTRA dose to 15 mg twice daily when coadministered with strong CYP3A4 inhibitors (e.g. ketoconazole) [see Drug Interactions ].

Dosage Modification for Concomitant Use with CYP3A4 Inducers

Avoid coadministration of COPIKTRA with strong CYP3A4 inducers.

Avoid coadministration of COPIKTRA with moderate CYP3A4 inducers. If coadministration with a moderate CYP3A4 inducer cannot be avoided, increase the COPIKTRA dose on Day 12 of coadministration with the moderate CYP3A4 inducer as recommended in Table 3.

After the inducer has been discontinued for at least 14 days, resume COPIKTRA at the dose taken prior to initiating the moderate CYP3A4 inducer [see Drug Interactions , Clinical Pharmacology ]

Pregnancy

Risk Summary

Based on findings from animal studies and the mechanism of action, COPIKTRA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ].

There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of duvelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes including embryo-fetal mortality (resorptions, post-implantation loss, and decreased viable fetuses), alterations to growth (lower fetal weights) and structural abnormalities (malformations) at maternal doses 10 times and 39 times the MRHD of 25 mg BID in rats and rabbits, respectively (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.  All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

In an embryo-fetal development study in rats, pregnant animals received daily oral doses of duvelisib of 0, 10, 50, 150 and 275 mg/kg/day during the period of organogenesis. Administration of duvelisib at doses ≥ 50 mg/kg/day resulted in adverse developmental outcomes including reduced fetal weights and external abnormalities (bent tail and fetal anasarca), and doses ≥ 150 mg/kg/day resulted in maternal toxicity including mortality and no live fetuses (100% resorption) in surviving dams.  In another study in pregnant rats receiving oral doses of duvelisib up to 35 mg/kg/day during the period of organogenesis, no maternal or embryo-fetal effects were observed.  The dose of 50 mg/kg/day in rats is approximately 10 -times the MRHD of 25 mg BID.

In an embryo-fetal development study in rabbits, pregnant animals received daily oral doses of duvelisib of 0, 25, 100, and 200 mg/kg/day during the period of organogenesis.  Administration of duvelisib at doses ≥ 100 mg/kg/day resulted in maternal toxicity (body weight losses or lower mean body weights and increased mortality) and adverse developmental outcomes (increased resorptions and post-implantation loss, abortion, and decreased numbers of viable fetuses).  In another study in pregnant rabbits receiving oral doses of duvelisib up to 75 mg/kg/day, no maternal or embryo-fetal effects were observed.  The dose of 100 mg/kg/day in rabbits is approximately 39 times the MRHD of 25 mg BID.

Lactation

Risk Summary

There are no data on the presence of duvelisib and/or its metabolites in human milk, the effects on the breastfed child, or on milk production.  Because of the potential for serious adverse reactions from duvelisib in a breastfed child, advise lactating women not to breastfeed while taking COPIKTRA and for 1 month after the last dose.

Females and Males of Reproductive Potential

COPIKTRA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1)]. 

Pregnancy Testing

Conduct pregnancy testing before initiation of COPIKTRA treatment.

Contraception

Females

Based on animal studies, COPIKTRA can cause fetal harm when administered to a pregnant woman.  Advise females of reproductive potential to use effective contraception during treatment with COPIKTRA and for 1 month after the last dose.

Males

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with COPIKTRA and for 1 month after the last dose.

Infertility

Based on testicular findings in animals, male fertility may be impaired by treatment with COPIKTRA [see Nonclinical Toxicology ( 13.1)].  There are no data on the effect of COPIKTRA on human fertility.

Pediatric Use

Safety and effectiveness of COPIKTRA have not been established in pediatric patients.  Pediatric studies have not been conducted.

Geriatric Use

Clinical trials of COPIKTRA included 270 patients (61%) that were 65 years of age and older and 104 (24%) that were 75 years of age and older.  No major differences in efficacy or safety were observed between patients less than 65 years of age and patients 65 years of age and older.