What is Copiktra (duvelisib), and how does it work?
Generic drug: duvelisib
Brand name: Copiktra
Copiktra (duvelisib) is a prescription medicine used to treat adults with:
- Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) who have received at least 2 prior therapies and they did not work or are no longer working.
- Follicular Lymphoma (FL) who have received at least 2 prior therapies and they did not work or are no longer working.
It is not known if Copiktra is safe and effective in children less than 18 years of age.
What are the side effects of Copiktra?
Copiktra may cause serious side effects, including:
- Elevated liver enzymes. Copiktra may cause abnormalities in liver blood tests. Your healthcare provider should do blood tests during your treatment with
Copiktra to check for liver problems. Tell your healthcare provider right away if you get any symptoms of liver problems, including yellowing of your skin or the white part of your eyes (jaundice), pain in the abdominal region, bruising or bleeding more easily than normal. - Low white blood cell count (neutropenia). Neutropenia is common with
Copiktra treatment and can sometimes be serious. Your healthcare provider should check your blood counts regularly during treatment with
Copiktra. Tell your healthcare provider right away if you have a fever or any signs of infection during treatment with
Copiktra.
Common side effects of Copiktra include:
- tiredness
- fever
- cough
- nausea
- upper respiratory infection
- bone and muscle pain
- low red blood cell count
These are not all the possible side effects of
Copiktra.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
WARNING
FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS
-
Fatal and/or serious infections occurred in 31% of Copiktra-treated patients.
Monitor for signs and symptoms of infection. Withhold Copiktra if infection is
suspected. - Fatal and/or serious diarrhea or colitis occurred in 18% of
Copiktra-treated patients. Monitor for the development of severe diarrhea or
colitis. Withhold Copiktra. - Fatal and/or serious cutaneous reactions
occurred in 5% of Copiktra-treated patients. Withhold Copiktra. - Fatal
and/or serious pneumonitis occurred in 5% of Copiktra-treated patients. Monitor
for pulmonary symptoms and interstitial infiltrates. Withhold Copiktra.
What is the dosage for Copiktra?
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.
Table 1: Copiktra Dose Modifications and Toxicity Management
ToxicityAdverse Reaction GradeRecommended ManagementNonhematologic Adverse ReactionsInfectionsGrade 3 or higher infection- Withhold Copiktra until resolved
- Resume at the same or reduced dose (see Table 2)
Clinical CMV infection or viremia (positive PCR or antigen test)
- Withhold Copiktra until resolved
- Resume at the same or reduced dose (see Table 2)
- If Copiktra is resumed, monitor patients for CMV reactivation (by PCR or antigen test) at least monthly
PJP
- For suspected PJP, withhold Copiktra until evaluated
- For confirmed PJP, discontinue Copiktra
Non-infectious Diarrhea or colitisMild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and responsive to antidiarrheal agents, OR Asymptomatic (Grade 1) colitis
- No change in dose
- Initiate supportive therapy with antidiarrheal agents as appropriate
- Monitor at least weekly until resolved
Mild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and unresponsive to antidiarrheal agents
- Withhold Copiktra until resolved
- Initiate supportive therapy with enteric acting steroids (e.g., budesonide)
- Monitor at least weekly until resolved
- Resume at a reduced dose (see Table 2)
Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR Severe diarrhea (Grade 3, >6 stools per day over baseline)
- Withhold Copiktra until resolved
- Initiate supportive therapy with enteric acting steroids (e.g., budesonide) or systemic steroids
- Monitor at least weekly until resolved
- Resume at a reduced dose (see Table 2)
- For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue Copiktra
Life-threatening
- Discontinue Copiktra
Cutaneous reactionsGrade 1-2
- No change in dose
- Initiate supportive care with emollients, antihistamines (for pruritus), or topical steroids
- Monitor closely
Grade 3
- Withhold Copiktra until resolved
- Initiate supportive care with emollients, antihistamines (for pruritus), or topical steroids
- Monitor at least weekly until resolved
- Resume at reduced dose (see Table 2)
- If severe cutaneous reaction does not improve, worsens, or recurs, discontinue Copiktra
Life-threatening
- Discontinue Copiktra
SJS, TEN, DRESS (any grade)
- Discontinue Copiktra
Pneumonitis without suspected infectious causeModerate (Grade 2) symptomatic pneumonitis
- Withhold Copiktra
- Treat with systemic steroid therapy
- If pneumonitis recovers to Grade 0 or 1, Copiktra may be resumed at reduced dose (see Table 2)
- If non-infectious pneumonitis recurs or patient does not respond to steroid therapy, discontinue Copiktra
Severe (Grade 3) or life-threatening pneumonitis
- Discontinue Copiktra
- Treat with systemic steroid therapy
ALT/AST elevation3 to 5 x upper limit of normal (ULN) (Grade 2)
- Maintain Copiktra dose
- Monitor at least weekly until return to < 3 x ULN
> 5 to 20 x ULN (Grade 3)
- Withhold Copiktra and monitor at least weekly until return to < 3 x ULN
- Resume Copiktra at same dose (first occurrence) or at a reduced dose for subsequent occurrence (see Table 2)
> 20 x ULN (Grade 4)
- Discontinue Copiktra
Hematologic Adverse ReactionsNeutropeniaAbsolute neutrophil count (ANC) 0.5 to 1.0 Gi/L
- Maintain Copiktra dose
- Monitor ANC at least weekly
ANC less than 0.5 Gi/L
- Withhold Copiktra.
- Monitor ANC until > 0.5 Gi/L
- Resume Copiktra at same dose (first occurrence) or at a reduced dose for subsequent occurrence (see Table 2)
ThrombocytopeniaPlatelet count 25 to < 50 Gi/L (Grade 3) with Grade 1 bleeding
- No change in dose
- Monitor platelet counts at least weekly
Platelet count 25 to < 50 Gi/L (Grade 3) with Grade 2 bleeding or Platelet count < 25 Gi/L (Grade 4)
- Withhold Copiktra
- Monitor platelet counts until > 25 Gi/L and resolution of bleeding (if applicable)
- Resume Copiktra at same dose (first occurrence) or resume at a reduced dose for subsequent occurrence (see Table 2)
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; CMV = cytomegalovirus; DRESS = drug reaction with eosinophilia and systemic systems; PCR = polymerase chain reaction; PJP = Pneumocystis jirovecii; pneumonia; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; CMV = cytomegalovirus; DRESS = drug reaction with eosinophilia and systemic systems; PCR = polymerase chain reaction; PJP = Pneumocystis jirovecii; pneumonia; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal
Recommended dose modification levels for Copiktra are presented in Table 2.
Table 2: Dose Modification Levels
Dose LevelDoseInitial Dose25 mg twice dailyDose Reduction15 mg twice dailySubsequent Dose ModificationDiscontinue Copiktra if patient is unable to tolerate 15 mg twice daily.Dose Modification For Concomitant Use With CYP3A4 Inhibitors
- Reduce Copiktra dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors (e.g. ketoconazole).
What drugs interact with Copiktra?
Effects Of Other Drugs On Copiktra
CYP3A Inducers
- Co-administration with a strong CYP3A inducer decreases duvelisib area under the
curve (AUC), which may reduce Copiktra efficacy. - Avoid co-administration of Copiktra with strong CYP3A4 inducers.
CYP3A Inhibitors
- Co-administration with a strong CYP3A inhibitor increases duvelisib AUC, which
may increase the risk of Copiktra toxicities. - Reduce Copiktra dose to 15 mg BID
when co-administered with a strong CYP3A4 inhibitor.
Effects Of Copiktra On Other Drugs
CYP3A Substrates
- Co-administration with Copiktra increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs.
- Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the co-administered sensitive CYP3A substrate.
Is Copiktra safe to use while pregnant or breastfeeding?
- Based on findings from animal studies and the mechanism of action,
Copiktra can cause fetal harm when administered to a pregnant woman. - 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, lactating women should not breastfeed while taking
Copiktra and for at least 1 month after the last dose.