Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Secura Bio Limited, 32 Molesworth Street, Dublin 2, Ireland
Copiktra monotherapy is indicated for the treatment of adult patients with:
Treatment with Copiktra should be conducted by a physician experienced in the use of anti-cancer therapies.
The recommended dose is 25 mg duvelisib twice daily. A cycle consists of 28 days. Treatment should be continued until disease progression or unacceptable toxicity.
Patients should be advised that if a dose is missed by less than 6 hours, the missed dose should be taken right away and the next dose should be taken as usual. If a dose is missed by more than 6 hours, patients should be advised to wait and to take the next dose at the usual time.
The dose of Copiktra should be reduced to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors (e.g. ketoconazole) [see section 4.5]. No dose adjustment is necessary when co-administered with moderate CYP3A4 inhibitors (e.g. fluconazole) but potential adverse reactions of duvelisib should be closely monitored.
Toxicities should be managed as 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 (25 mg or 15 mg twice daily) |
| Clinical CMV infection or viremia (positive PCR or antigen test) | • Withhold Copiktra until resolved • Resume at the same or reduced dose (25 mg or 15 mg twice daily) • If Copiktra is resumed, monitor patients for CMV reactivation (by PCR or antigen test) at least monthly. In clinical studies iNHL, FL (IPI-145-06) and CLL/SLL (IPI-145-07 the outcome of starting at same dose or reduction are comparable | |
| PJP | • For suspected PJP, withhold Copiktra until evaluated • For confirmed PJP, discontinue Copiktra | |
| Non-infectious diarrhoea or colitis | Mild/moderate diarrhoea (Grade 1-2, up to 6 stools per day over baseline) and responsive to anti- diarrhoeal agents, OR Asymptomatic (Grade 1) colitis | • No change in dose • Initiate supportive therapy with anti-diarrhoeal agents as appropriate • Monitor at least weekly until resolved |
| Mild/moderate diarrhoea (Grade 1-2, up to 6 stools per day over baseline) and unresponsive to anti-diarrhoeal 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 (15 mg twice daily) | |
| Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR Severe diarrhoea (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 (15 mg twice daily) • For recurrent Grade 3 diarrhoea 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 • Review all concomitant medications and discontinue any medication potentially contributing to the event • Initiate supportive care with steroids (topical or systemic) and antihistamines for pruritus • Monitor at least weekly until resolved • Resume at reduced dose (15 mg twice daily) • If severe cutaneous reaction does not improve, worsens, or recurs, discontinue Copiktra | |
| Life-threatening | • Discontinue Copiktra | |
| SJS, TEN, DRESS (any grade) | • Discontinue Copiktra for any grade | |
| 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 (15 mg twice daily) • 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 (25 mg twice daily) for first occurrence or at a reduced dose (15 mg twice daily) for subsequent occurrence | |
| > 20 × ULN (Grade 4) | • Discontinue Copiktra | |
| Neutropenia | Absolute neutrophil count (ANC) 0.5 to 1.0 × 109/L | • Maintain Copiktra dose • Monitor ANC at least weekly |
| ANC less than 0.5 × 109/L | • Withhold Copiktra. • Monitor ANC until > 0.5 × 109/L • Resume Copiktra at same dose (25 mg twice daily) for first occurrence or at a reduced dose (15 mg twice daily) for subsequent occurrence | |
| Thrombocytopenia | Platelet count 25 to < 50 × 109/L (Grade 3) with Grade 1 bleeding | • No change in dose • Monitor platelet counts at least weekly |
| Platelet count 25 to < 50 × 109/L (Grade 3) with Grade 2 bleeding or Platelet count < 25 × 109/L (Grade 4) | • Withhold Copiktra • Monitor platelet counts until ≥ 25 × 109/L and resolution of bleeding (if applicable) • Resume Copiktra at the same dose (25 mg twice daily) for first occurrence or resume at a reduced dose (15 mg twice daily) for subsequent occurrence | |
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 Note: Doses withheld for >42 days due to treatment-related toxicity will result in permanent discontinuation from treatment
No specific dose adjustment is required for elderly patients (aged ≥65 years) (see section 5.2).
No dose adjustment is required for patients with mild and moderate renal impairment. No data are available for severe and end-stage renal impairment with or without dialysis, (see sections 5.2).
No dose adjustment of the starting dose is required for patients with hepatic impairment Child Pugh Class A, B, and C (see sections 4.4 and 5.2).
The safety and efficacy of duvelisib in children aged 0 to 18 years has not been established. No data are available. There is no relevant use of duvelisib in the paediatric population for the indication of CLL and FL.
Copiktra is for oral use and can be taken with or without food. The capsules should be swallowed whole. Patients should be advised not to open, break, or chew the capsules.
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8). In case of overdose, general supportive measures and treatment should be provided. The patient should be monitored for signs and symptoms, laboratory parameters, and vital signs.
Copiktra 15 mg hard capsules: 4 years.
Copiktra 25 mg hard capsules: 5 years.
Store below 30°C.
Store in the original package in order to protect from light.
Copiktra 15 mg hard capsules:
Child-resistant PVC-PE-PCTFE/Aluminium blisters.
Pack size: 28 days carton containing 56 capsules (2 blisters with 28 capsules each).
Copiktra 25 mg hard capsules:
Child-resistant PVC-PE-PCTFE/Aluminium blisters.
Pack size: 28 days carton containing 56 capsules (2 blisters with 28 capsules each).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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