ZYDELIG® Adverse
Event
Monitoring
and Management

AEs may be addressed with dose modifications Dose modifications include dose interruption, reduction, and/or treatment discontinuation

Monitoring of Lab Abnormalities and Adverse Events
Monitor
ALT/AST
Monitor every
2 weeks
First
3 months
Monitor every
4 weeks
Next
3 months
Monitor every
1 to 3 months
Thereafter

ALT/AST elevations were generally observed within the first 3 months of treatment

  • ALT/AST elevations were reversible with dose interruptions
Monitor for
infections
Monitor for
symptoms of
sepsis or
pneumonia, CMV
or viremia,
and PJP
For duration
of treatment
Monitor
ANC
Monitor every
2 weeks
First
6 months
Monitor for
severe
cutaneous
reactions
Monitor for
development of severe
cutaneous reactions
For duration
of treatment

AE=adverse event; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate aminotransferase; CMV=cytomegalovirus; PJP=Pneumocystis jirovecii pneumonia.

Management of Lab Abnormalities and Adverse Events
Hepatotoxicity
Adverse Event
Management
Adverse Event & Management

ALT/AST >3-5 × ULN or
bilirubin >1.5-3 × ULN

  • Maintain ZYDELIG dose
  • Monitor at least weekly until ≤1 × ULN

ALT/AST >5-20 × ULN or
bilirubin >3-10 × ULN

  • Withhold ZYDELIG
  • Monitor at least weekly until ≤1 × ULN
  • May resume ZYDELIG at 100 mg twice daily

74% of patients who were rechallenged at a lower
dose did not experience a recurrence.1

ALT/AST >20 × ULN or
bilirubin >10 × ULN

  • Discontinue ZYDELIG
Diarrhea
Adverse Event
Management
Adverse Event & Management

Moderate diarrhea*

  • Maintain ZYDELIG dose
  • Monitor at least weekly until resolved

Severe diarrhea or
hospitalization

  • Withhold ZYDELIG
  • May treat with corticosteroids (eg, budesonide
    or other oral or intravenous corticosteroid therapy)
  • Monitor weekly until resolved, then may resume
    ZYDELIG at 100 mg twice daily

Life-threatening diarrhea

  • Discontinue ZYDELIG

*Moderate diarrhea: increase of 4-6 stools per day over baseline.

Severe diarrhea: increase of ≥7 stools per day over baseline. Severe diarrhea responded poorly to antimotility agents.

Cytopenias
Adverse Event
Management
Adverse Event & Management

ANC 1.0 to <1.5 x 109/L or
platelets 50 to <75 x 109/L

  • Maintain ZYDELIG dose

ANC 0.5 to <1.0 x 109/L or
platelets 25 to <50 x 109/L

  • Maintain ZYDELIG dose
  • Monitor at least weekly

ANC <0.5 x 109/L or
platelets <25 x 109/L

  • Interrupt ZYDELIG
  • Monitor counts at least weekly until resolution
    (ANC ≥0.5 x 109/L or platelets ≥25 x 109/L)
  • May resume ZYDELIG at 100 mg twice daily
Infections
Adverse Event
Management
Adverse Event & Management

Grade 3 or higher sepsis or pneumonia

  • Interrupt ZYDELIG until infection has resolved

Evidence of CMV infection or viremia

  • Interrupt ZYDELIG until infection has resolved
  • If ZYDELIG is resumed, monitor patients (by PCR or antigen test) for CMV reactivation at least monthly

Evidence of PJP infection

  • Interrupt ZYDELIG
  • Discontinue ZYDELIG if PJP infection is confirmed
Symptomatic Pneumonitis, Intestinal Perforation, Severe Cutaneous
Reactions, Anaphylaxis
Adverse Event
Management
Adverse Event & Management

Any symptomatic pneumonitis,
intestinal perforation, severe
cutaneous reactions,
or anaphylaxis

  • Discontinue ZYDELIG
  • Pneumonitis thought to be caused by ZYDELIG
    has been treated with dose discontinuation
    and corticosteroids
Other Toxicities
Adverse Event
Management
Adverse Event & Management

Other severe or life-threatening
toxicities

  • Withhold ZYDELIG
  • If toxicity resolves, may resume ZYDELIG at 100 mg
    twice daily
  • If toxicity recurs, permanently discontinue ZYDELIG

PCR=polymerase chain reaction.