S:6.75”
ZYDELIG® (idelalisib) tablets, for oral use
Brief Summary of full Prescribing Information. See full Prescribing
Information. Rx Only.
WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE
DIARRHEA, COLITIS, PNEUMONITIS, and INTESTINAL PERFORATION
• Fatal and/or serious hepatotoxicity occurred in 14% of ZYDELIG-treated
patients. Monitor hepatic function prior to and during treatment.
Interrupt and then reduce or discontinue ZYDELIG as recommended
[See Dosage and Administration, Warnings and Precautions].
• Fatal and/or serious and severe diarrhea or colitis occurred in 14% of
ZYDELIG-treated patients. Monitor for the development of severe
diarrhea or colitis. Interrupt and then reduce or discontinue ZYDELIG as
recommended [See Dosage and Administration, Warnings and Precautions].
• Fatal and serious pneumonitis can occur in ZYDELIG-treated
patients. Monitor for pulmonary symptoms and bilateral interstitial
infiltrates. Interrupt or discontinue ZYDELIG as recommended
[See Dosage and Administration, Warnings and Precautions].
• Fatal and serious intestinal perforation can occur in ZYDELIGtreated patients. Discontinue ZYDELIG for intestinal perforation
[See Warnings and Precautions].
INDICATIONS AND USAGE:
DOSAGE AND ADMINISTRATION:
See Warnings and Precautions, Adverse Reactions, and Use in Specific
Populations for additional information.
Adult Starting Dose: One 150 mg tablet taken orally twice daily (BID), swallowed
whole with or without food. Continue treatment until disease progression or
unacceptable toxicity. The optimal and safe dosing regimen for patients who
required treatment longer than several months is unknown.
Dose Modifications:
• Pneumonitis: discontinue ZYDELIG for any symptomatic pneumonitis
• Hepatotoxicity:
– ALT/AST >3 to 5x ULN or bilirubin >1.5 to 3x ULN: maintain ZYDELIG dose;
monitor weekly until ≤1x ULN
– ALT/AST >5 to 20x ULN or bilirubin >3 to 10x ULN: withhold ZYDELIG;
monitor weekly until ≤1x ULN then resume ZYDELIG 100 mg BID
– ALT/AST >20x ULN or bilirubin >10x ULN: permanently discontinue ZYDELIG
• Diarrhea:
– Moderate (increase of 4-6 stools/day over baseline): maintain ZYDELIG dose;
monitor weekly until resolved
– Severe (increase of ≥7 stools/day over baseline) or hospitalization: withhold
ZYDELIG; monitor weekly until resolved then resume ZYDELIG 100 mg BID
– Life-threatening: permanently discontinue ZYDELIG
• Neutropenia:
– ANC 1 to <1.5 Gi/L: maintain ZYDELIG dose
– ANC 0.5 to <1 Gi/L: maintain ZYDELIG dose; monitor weekly
– ANC <0.5 Gi/L: withhold ZYDELIG; monitor weekly until ≥0.5 Gi/L then
resume ZYDELIG 100 mg BID
• Thrombocytopenia:
– Platelets 50 to <75 Gi/L: maintain ZYDELIG dose
– Platelets 25 to <50 Gi/L: maintain ZYDELIG dose; monitor weekly
– Platelets <25 Gi/L: withhold ZYDELIG; monitor weekly until ≥25 Gi/L then
resume ZYDELIG 100 mg BID
• For other severe or life-threatening toxicities, withhold ZYDELIG until toxicity is
resolved and reduce dose to 100 mg BID if resuming treatment. Permanently
discontinue ZYDELIG if severe or life-threatening toxicities recur upon rechallenge.
History of serious allergic reactions including anaphylaxis and toxic epidermal
necrolysis (TEN).
WARNINGS AND PRECAUTIONS:
Fatal and/or serious hepatotoxicity occurred in 14% of ZYDELIG-treated
patients. ALT or AST >5x ULN have occurred, usually within the first 12 weeks of
treatment and were reversible with dose interruption. Upon resuming treatment
at a lower dose, 26% of patients had recurrence of ALT and AST elevations.
Discontinue ZYDELIG for recurrent hepatotoxicity. Avoid concurrent use of
ZYDELIG with hepatotoxic drugs. In all patients, monitor ALT and AST every
2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every
1 to 3 months thereafter. If ALT or AST >3x ULN, monitor weekly until elevation
resolves; if ALT or AST >5x ULN, withhold ZYDELIG and monitor AST, ALT and
total bilirubin weekly until elevation resolves [See Dosage and Administration].
Severe diarrhea or colitis (≥Grade 3) occurred in 14% of ZYDELIG-treated
patients across clinical trials. ZYDELIG-induced diarrhea can occur at any time
and responds poorly to antimotility agents. Median time to resolution ranged
between 1 week and 1 month following ZYDELIG interruption with or without
enteric or systemic corticosteroids. Avoid concurrent use of ZYDELIG with drugs
that cause diarrhea. [See Dosage and Administration].
Fatal and serious pneumonitis occurred in ZYDELIG-treated patients. Patients
taking ZYDELIG who present with pulmonary symptoms (e.g., cough, dyspnea,
hypoxia, interstitial infiltrates, >5% decrease in oxygen saturation) should
be evaluated for pneumonitis. If pneumonitis is suspected, withhold ZYDELIG
until etiology of pulmonary symptoms has been determined. Patients thought to
have ZYDELIG-induced pneumonitis were treated with ZYDELIG discontinuation
and corticosteroids.
Fatal and serious intestinal perforation occurred in ZYDELIG-treated patients.
At the time of perforation, some patients had moderate to severe diarrhea.
Advise patients to promptly report any new or worsening abdominal pain, chills,
fever, nausea, or vomiting. Permanently discontinue ZYDELIG in patients who
experience intestinal perforation.
Severe Cutaneous Reactions: One case of TEN occurred in a study of ZYDELIG in
combination with rituximab and bendamustine. Other severe or life-threatening
(Grade ≥3) cutaneous reactions (dermati \