Source: FDA, National Drug Code (US) Revision Year: 2019
COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory CLL or SLL after at least two prior therapies.
COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory FL after at least two prior systemic therapies.
This indication is approved under accelerated approval based on overall response rate (ORR) [see Clinical Studies (14.2)]; continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
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.
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.
Manage toxicities per Table 1 with dose reduction, treatment hold, or discontinuation of COPIKTRA.
Table 1. COPIKTRA Dose Modifications and Toxicity Management:
| Toxicity | Adverse Reaction Grade | Recommended Management |
|---|---|---|
| Nonhematologic Adverse Reactions | ||
| Infections | Grade 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 colitis | Mild/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 reactions | Grade 1-2 | • No change in dose • Initiate supportive care with emollients, anti-histamines (for pruritus), or topical steroids • Monitor closely |
| Grade 3 | • Withhold COPIKTRA until resolved • Initiate supportive care with emollients, anti-histamines (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 cause | Moderate (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 elevation | 3 to 5 × upper limit of normal (ULN) (Grade 2) | • Maintain COPIKTRA dose • Monitor at least weekly until return to <3 × ULN |
| >5 to 20 × ULN (Grade 3) | • Withhold COPIKTRA and monitor at least weekly until return to <3 × ULN • Resume COPIKTRA at same dose (first occurrence) or at a reduced dose for subsequent occurrence (see Table 2) | |
| >20 × ULN (Grade 4) | • Discontinue COPIKTRA | |
| Hematologic Adverse Reactions | ||
| Neutropenia | Absolute 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) | |
| Thrombocytopenia | Platelet 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
Recommended dose modification levels for COPIKTRA are presented in Table 2.
Table 2. Dose Modification Levels:
| Dose Level | Dose |
|---|---|
| Initial Dose | 25 mg twice daily |
| Dose Reduction | 15 mg twice daily |
| Subsequent Dose Modification | Discontinue COPIKTRA if patient is unable to tolerate 15 mg twice daily. |
Reduce COPIKTRA dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors (e.g. ketoconazole) [see Drug Interactions (7.1)].
Store at 20° to 25°C (68° to 77°F), with excursions permitted at 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Retain in original package until dispensing. Dispense blister packs in original container.
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