Copiktra (duvelisib): Leukemia Medication Side Effects & Dosage

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:

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.