Adverse event monitoring and management

Identifying and addressing AEs early may enable patients to continue benefiting from ZYDELIG®-based therapy*

Monitoring schedule

ANC
First 6 months:
every 2 weeks

Monitor at least weekly while neutrophil counts are <1.0 × 109/L

ALT/AST
First 3 months:
Every 2 weeks
Next 3 months:
Every 4 weeks
Thereafter:
Every 1 to 3 months

ALT/AST elevations were generally observed within the first 12 weeks of treatment

  • Elevations were reversible with dose interruption
Diarrhea
Monitor for severe diarrhea or
colitis throughout therapy

Diarrhea can occur at any time

  • Mild to moderate diarrhea: median time to onset was 1.5 months (range, 0.0-15.2 months)2
  • Severe diarrhea: median time to onset was 7.1 months (range, 0.5-29.8 months)2
Pneumonitis
Monitor for symptomatic pneumonitis and
organizing pneumonia throughout therapy
  • Pneumonitis: time to onset ranged from <1 to 15 months
  • Monitor for pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic exam, or a decline by more than 5% in oxygen saturation
Infections
Monitor for signs and symptoms of infection throughout therapy

Serious or fatal PJP or CMV occurred in <1% of patients treated with ZYDELIG

  • Provide PJP prophylaxis during treatment with ZYDELIG
  • Regular clinical and laboratory monitoring for CMV infection is recommended in patients with history of CMV infection or positive CMV serology at the start of treatment with ZYDELIG
Severe cutaneous reactions
Monitor for severe cutaneous
reactions throughout therapy

Reinitiating ZYDELIG at 100 mg BID

Follow the ZYDELIG USPI AE management guidelines when determining if reinitiating therapy multiple times is appropriate

Graphic applies to yellow WITHHOLD or INTERRUPT events in the table below

START

ZYDELIG at recommended dose 150 mg po BID

Image of ZYDELIG 150 mg pill

1ST OCCURRENCE
of toxicity:

Interrupt/withhold
ZYDELIG and monitor
at least weekly until
toxicity has resolved

REINITIATE

ZYDELIG at 100 mg
po BID

Image of ZYDELIG 100 mg pill

2ND OCCURRENCE
of toxicity or beyond:

Interrupt/withhold
ZYDELIG and monitor
at least weekly until
toxicity has resolved

REINITIATE

ZYDELIG at 100 mg
po BID

Image of ZYDELIG 100 mg pill

Pill images are not actual size.

For other severe or life-threatening toxicities related to ZYDELIG:

Withhold drug until toxicity is resolved. If resuming ZYDELIG after interruption for other severe or life-threatening toxicities, reduce the dose to 100 mg twice daily. Discontinue ZYDELIG permanently for recurrence of other severe or life-threatening ZYDELIG-related toxicity upon rechallenge.

In clinical studies, dose reductions were reported in 15% of CLL patients and in 34% of patients in the trial that included follicular lymphoma3‡

For patients who experienced dose interruptions, many were able to reinitiate ZYDELIG without AE recurrence

Among patients experiencing grade 3 hepatotoxicity§:

74%
who reinitiated at a lower dose did not have a recurrence
  • Serious and sometimes fatal hepatotoxicity occurred in 18% of follicular lymphoma and 16% of CLL patients

Among patients experiencing grade ≥3 diarrhea or colitis2:

67%
were reinitiated at a lower dose
58%
of them successfully
  • Grade ≥3 diarrhea or colitis occurred in 14% of follicular lymphoma and 20% of CLL patients

Adverse reactions resulted in interruption for 42 (38%) CLL patients.

Discontinuation rate due to AEs was 20% in the trial that included follicular lymphoma.3‡ Adverse reactions resulted in interruption or discontinuation for 78 of 146 (53%) patients.


Knowing when to interrupt or discontinue ZYDELIG

KEY
  • KEY:
  • MAINTAIN
  • WITHHOLD or INTERRUPT
  • DISCONTINUE
Toxicity
Setting or severity
Management recommendation
Any symptomatic pneumonitis or organizing pneumonia
DISCONTINUE ZYDELIG permanently in patients with any severity of symptomatic pneumonitis or organizing pneumonia and initiate appropriate treatment with corticosteroids.
>3-5 × ULN
MAINTAIN ZYDELIG dose. Monitor at least weekly until ≤1 × ULN.
>5-20 × ULN
WITHHOLD ZYDELIG. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume ZYDELIG at 100 mg BID.
>20 × ULN
DISCONTINUE ZYDELIG permanently.
>1.5-3 × ULN
MAINTAIN ZYDELIG dose. Monitor at least weekly until ≤1 × ULN.
>3-10 × ULN
WITHHOLD ZYDELIG. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume ZYDELIG at 100 mg BID.
>10 × ULN
DISCONTINUE ZYDELIG permanently.
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/IV corticosteroid therapy).4 Monitor at least weekly until resolved, then may resume ZYDELIG at 100 mg BID.
Life-threatening diarrhea
DISCONTINUE ZYDELIG permanently.
ANC 1.0 to <1.5 × 109/L
MAINTAIN ZYDELIG dose.
ANC 0.5 to <1.0 × 109/L
MAINTAIN ZYDELIG dose. Monitor ANC at least weekly.
ANC <0.5 × 109/L
INTERRUPT ZYDELIG. Monitor ANC at least weekly until ANC ≥0.5 × 109/L, then may resume ZYDELIG at 100 mg BID.
Platelets 50 to <75 × 109/L
MAINTAIN ZYDELIG dose.
Platelets 25 to <50 × 109/L
MAINTAIN ZYDELIG dose. Monitor platelet counts at least weekly.
Platelets <25 × 109/L
INTERRUPT ZYDELIG. Monitor platelet count at least weekly. May resume ZYDELIG at 100 mg BID when platelets ≥25 × 109/L.
Grade 3 or higher sepsis or pneumonia
INTERRUPT ZYDELIG until infection has resolved.
Evidence of CMV infection or viremia
INTERRUPT ZYDELIG in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia 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 in patients with suspected PJP infection of any grade.
Confirmation of PJP infection
DISCONTINUE ZYDELIG permanently if PJP infection is confirmed.

For other severe or life-threatening toxicities related to ZYDELIG:

Withhold drug until toxicity is resolved. If resuming ZYDELIG after interruption for other severe or life-threatening toxicities, reduce the dose to 100 mg twice daily. Discontinue ZYDELIG permanently for recurrence of other severe or life-threatening ZYDELIG-related toxicity upon rechallenge.


Image of dosing guide

Dosing guide

Download PDF

ZYDELIG dosing

Learn more

Healthcare professional
resources

Learn more

Patient resources

Learn more

*Please see full Prescribing Information for a complete list of AEs.
†Mild diarrhea=grade 1: increase of <4 stools per day over baseline; moderate diarrhea=grade 2: increase of 4-6 stools per day over baseline; severe diarrhea=grade 3: increase of ≥7 stools per day over baseline; life-threatening diarrhea=grade 4.5
‡Follicular lymphoma dose reduction data and discontinuation rate (20%) data reflect exposure to ZYDELIG monotherapy in 125 patients with iNHL, including 72 patients with follicular lymphoma.3 Rates of serious and fatal hepatotoxicity, grade ≥3 diarrhea or colitis, and interruption or discontinuation in 53% of patients reflect exposure to ZYDELIG monotherapy in 146 patients with iNHL, including patients with follicular lymphoma.
§ALT/AST elevations were generally observed within the first 12 weeks of treatment.

AE=adverse event; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate aminotransferase; BID=twice daily; CLL=chronic lymphocytic leukemia; CMV=cytomegalovirus; iNHL= indolent non-Hodgkin lymphoma; IV=intravenous; PCR=polymerase chain reaction; PJP=Pneumocystis jirovecii pneumonia; po=orally; SLL=small lymphocytic lymphoma; ULN=upper limit of normal; USPI=United States Prescribing Information.

References:

  1. ZYDELIG® (idelalisib) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; rev January 2018.
  2. Data on file. Gilead Sciences, Inc. 2018.
  3. Gopal AK, Kahl BS, de Vos S, et al. PI3K inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008-1018.
  4. Coutré SE, Barrientos JC, Brown JR, et al. Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma. 2015;56(10):2779-2786.
  5. US Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE), Version 4.0. Published May 28, 2009 (v4.03: June 14, 2010).