Dosage of Idelalisib

Recommended Dosage

The recommended dose of idelalisib is 150 mg, administered orally twice daily, with or without food, until disease progression or unacceptable toxicity occurs. The optimal and safe dosing regimen for patients receiving treatment for more than several months has not been established.

Swallow the tablets whole.

If a scheduled dose of idelalisib is missed by less than 6 hours, take the missed dose as soon as possible and then resume the next dose according to the original schedule. If a dose is missed by more than 6 hours, skip the missed dose and take the next dose at the regular time.

Dosage Adjustment for Adverse Reactions

The table below lists dosage adjustment recommendations for specific adverse reactions.

For other severe or life-threatening adverse reactions, suspend idelalisib until recovery. If resuming idelalisib after interruption due to other severe or life-threatening toxicities, reduce the dose to 100 mg orally twice daily. If other severe or life-threatening idelalisib-related toxicities recur after rechallenge, permanently discontinue idelalisib.

Dosage Adjustment Guidelines:

Hepatotoxicity

Elevated ALT/AST:

If ALT/AST is greater than 3 to 5 times the upper limit of normal (ULN): Maintain the idelalisib dose. Monitor at least weekly until levels are ≤1×ULN.

If ALT/AST is greater than 5 to 20×ULN: Suspend idelalisib. Monitor at least weekly until ALT/AST is ≤1×ULN, then idelalisib may be resumed at 100 mg twice daily.

If ALT/AST is greater than 20×ULN: Permanently discontinue idelalisib.

Elevated Bilirubin:

If bilirubin is greater than 1.5 to 3×ULN: Maintain the idelalisib dose. Monitor at least weekly until levels are ≤1×ULN.

If bilirubin is greater than 3 to 10×ULN: Suspend idelalisib. Monitor at least weekly until bilirubin is ≤1×ULN, then idelalisib may be resumed at 100 mg twice daily.

If bilirubin is greater than 10×ULN: Permanently discontinue idelalisib.

Diarrhea

Moderate diarrhea: Maintain the idelalisib dose. Monitor at least weekly until resolution.

Severe diarrhea or diarrhea requiring hospitalization: Suspend idelalisib. Monitor at least weekly until resolution, then idelalisib may be resumed at 100 mg twice daily.

Life-threatening diarrhea: Permanently discontinue idelalisib.

Pneumonitis

Any symptomatic pneumonitis: Discontinue idelalisib.

Infections

Grade 3 or higher sepsis or pneumonitis: Interrupt idelalisib until the infection resolves.

Evidence of cytomegalovirus (CMV) infection or viremia: Interrupt idelalisib during evidence of active CMV infection or viremia of any grade until viremia resolves. If resuming idelalisib, monitor patients for CMV reactivation at least monthly via PCR or antigen testing.

Evidence of Pneumocystis jirovecii infection: Interrupt idelalisib if Pneumocystis jirovecii infection is suspected at any grade. Permanently discontinue idelalisib if Pneumocystis jirovecii infection is confirmed.

Intestinal Perforation

Evidence of intestinal perforation: Permanently discontinue idelalisib in patients who experience intestinal perforation.

Severe Cutaneous Reactions

Suspected/confirmed Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or other severe or life-threatening cutaneous reactions: Interrupt idelalisib if SJS, TEN, or DRESS is suspected until the cause of the reaction is determined. Permanently discontinue idelalisib if SJS, TEN, DRESS, or other severe or life-threatening cutaneous reactions are confirmed.

Hypersensitivity Reactions

Evidence of hypersensitivity reaction: Permanently discontinue idelalisib in patients who experience severe hypersensitivity reactions.

Neutropenia

Absolute neutrophil count (ANC) 1.0 to <1.5 Gi/L: Maintain the idelalisib dose.

ANC 0.5 to <1.0 Gi/L: Maintain the idelalisib dose. Monitor ANC at least weekly.

ANC <0.5 Gi/L: Interrupt idelalisib. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then idelalisib may be resumed at 100 mg twice daily.

Thrombocytopenia

Platelet count 50 to <75 Gi/L: Maintain the idelalisib dose.

Platelet count 25 to <50 Gi/L: Maintain the idelalisib dose. Monitor platelet count at least weekly.

Platelet count <25 Gi/L: Interrupt idelalisib. Monitor platelet count at least weekly. When platelet count ≥25 Gi/L, idelalisib may be resumed at 100 mg twice daily.

Dosage adjustment for lymphocytosis is not recommended, as this has been observed in some patients taking idelalisib. This observed lymphocytosis is a pharmacodynamic effect and should not be considered disease progression in the absence of other clinical findings.

FDA，2022.02