Dosing and Adverse Reaction Management
Dosing and Administration
Oral administration offers the convenience of taking their treatment at home or away 8
Dosing guidelines:
- COPIKTRA is an oral monotherapy taken in 28-day cycles until disease progression or unacceptable toxicity
- 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
Prophylaxis recommendations:
- Provide prophylaxis for Pneumocystis jirovecii pneumonia (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 permanently discontinue if PJP is confirmed
- Consider prophylactic antivirals during COPIKTRA treatment to prevent cytomegalovirus (CMV) infection, including CMV reactivation
Dose modifications:
- Reduce the dose of COPIKTRA to 15 mg BID when coadministered with strong CYP3A4 inhibitors (eg, ketoconazole)
- For select adverse reaction management, reduce COPIKTRA to 15 mg twice daily. Discontinue COPIKTRA if patient is unable to tolerate 15 mg twice daily. Please see the adverse reaction management tables for specific dose modification information
Adverse Reaction Management
Recommended management plans for adverse reactions based on severity.1
GRADE 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 COPIKTRA at reduced dose
- DISCONTINUE COPIKTRA if severe cutaneous reaction does not improve, worsens, or recurs
LIFE-THREATENING
- DISCONTINUE COPIKTRA
SJS, TEN, DRESS (ANY GRADE)
- DISCONTINUE COPIKTRA
MILD/MODERATE DIARRHEA (GRADE 1-2) AND RESPONSIVE TO ANTIDIARRHEAL AGENTS
- NO CHANGE in dose
- INITIATE supportive therapy with antidiarrheal agents as appropriate
- MONITOR at least weekly until resolved
ASYMPTOMATIC COLITIS (GRADE 1)
- NO CHANGE in dose
- INITIATE supportive therapy with antidiarrheal agents as appropriate
- MONITOR at least weekly until resolved
MILD/MODERATE DIARRHEA (GRADE 1-2) AND UNRESPONSIVE TO ANTIDIARRHEAL AGENTS
- WITHHOLD COPIKTRA until resolved
- INITIATE supportive therapy with enteric-acting steroids (eg, budesonide)
- MONITOR at least weekly until resolved
- RESUME COPIKTRA at reduced dose
ABDOMINAL PAIN, STOOL WITH MUCUS OR BLOOD, CHANGE IN BOWEL HABITS, PERITONEAL SIGNS
- WITHHOLD COPIKTRA until resolved
- INITIATE supportive therapy with enteric-acting steroids (eg, budesonide) or systemic steroids
- MONITOR at least weekly until resolved
- RESUME COPIKTRA at reduced dose
- DISCONTINUE COPIKTRA for recurrent Grade 3 diarrhea or recurrent colitis of any grade
SEVERE DIARRHEA (GRADE 3)
- WITHHOLD COPIKTRA until resolved
- INITIATE supportive therapy with enteric-acting steroids (eg, budesonide) or systemic steroids
- MONITOR at least weekly until resolved
- RESUME COPIKTRA at reduced dose
- DISCONTINUE COPIKTRA for recurrent Grade 3 diarrhea
LIFE-THREATENING
- DISCONTINUE COPIKTRA
MODERATE (GRADE 2)
- WITHHOLD COPIKTRA
- TREAT with systemic steroid therapy
- RESUME COPIKTRA at reduced dose if pneumonitis recovers to Grade 0 or 1
- DISCONTINUE COPIKTRA if non-infectious pneumonitis recurs or patient does not respond to steroid therapy
SEVERE (GRADE 3) OR LIFE-THREATENING
- DISCONTINUE COPIKTRA
- TREAT with systemic steroid therapy
GRADE 3 OR HIGHER INFECTION
- WITHHOLD COPIKTRA until resolved
- RESUME COPIKTRA at same or reduced dose
CLINICAL CMV INFECTION OR VIREMIA
- WITHHOLD COPIKTRA until resolved
- RESUME COPIKTRA at same or reduced dose
- MONITOR patients for CMV reactivation (by PCR or antigen test) at least monthly if COPIKTRA is resumed
PJP
- WITHHOLD COPIKTRA until evaluated for suspected PJP
- DISCONTINUE COPIKTRA for confirmed PJP
3 TO 5 X ULN (GRADE 2)
- MAINTAIN COPIKTRA dose
- MONITOR at least weekly until return to less than <3 x ULN
>5 TO 20 X ULN (GRADE 3)
- WITHHOLD COPIKTRA
- MONITOR at least weekly until return to less than <3 x ULN
- RESUME COPIKTRA at same dose (first occurrence) or at a reduced dose for subsequent occurrence
>20 X ULN (GRADE 4)
- DISCONTINUE COPIKTRA
ANC 0.5 TO 1.0 Gi/L
- MAINTAIN COPIKTRA dose
- MONITOR ANC at least weekly
ANC <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
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
- WITHHOLD COPIKTRA
- MONITOR platelet counts until ≥25 Gi/L and resolution of bleeding (if applicable)
- RESUME COPIKTRA at same dose (first occurrence) or at a reduced dose for subsequent occurrences
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 at a reduced dose for subsequent occurrences
ALT, alanine transaminase; ANC, absolute neutrophil count; AR, adverse reaction; AST, aspartate transaminase; CLL, chronic lymphocytic leukemia; CMV, cytomegalovirus; DRESS, drug rash with eosinophilia and systemic symptoms; PCR, polymerase chain reaction; PJP, Pneumocystis jirovecii pneumonia; SJS, Stevens-Johnson syndrome; SLL, small lymphocytic lymphoma; TEN, toxic epidermal necrolysis; ULN, upper limit normal.
