Idelalisib

Idelalisib is used to treat chronic lymphocytic leukemia, follicular B-cell non-Hodgkin lymphoma, and small lymphocytic lymphoma.

Idelalisib is available under the following different brand names: Zydelig.

Dosages of Idelalisib:

Dosage Forms and Strengths

• 100 mg
• 150 mg

Dosage Considerations – Should be Given as Follows:

Chronic Lymphocytic Leukemia

• Indicated, in combination with rituximab, for relapsed chronic lymphocytic leukemia (CLL) in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities
• Starting dose: 150 mg orally twice daily; continue treatment until disease progression or unacceptable toxicity

Follicular B-cell Non-Hodgkin Lymphoma

• Accelerated approval for relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies
• Starting dose: 150 mg orally twice daily; continue treatment until disease progression or unacceptable toxicity

Small Lymphocytic Lymphoma

• Accelerated approval for relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies
• Starting dose: 150 mg orally twice daily; continue treatment until disease progression or unacceptable toxicity

Dosage Modifications

• Pneumonitis: Discontinue any severity of symptomatic pneumonitis
• CrCl 15 mL/minute or greater: No dose adjustment required

ALT/AST

• Greater than 3-5 x ULN: Maintain dose; monitor at least weekly until up to 1 x ULN
• Greater than 5-20 x ULN: Withhold idelalisib; monitor ALT/AST at least weekly until up to 1 x ULN, then resume at 100 mg twice daily
• Greater than 20 x ULN: Permanently discontinue

Bilirubin

• Greater than 1.5-3 x ULN: Maintain dose; monitor at least weekly until up to 1 x ULN
• Greater than 3-10 x ULN: Withhold idelalisib; monitor bilirubin at least weekly until up to 1 x ULN, then resume at 100 mg twice daily
• Greater than 10 x ULN: Permanently discontinue

Diarrhea

• Moderate: Maintain dose; monitor at least weekly until resolved
• Severe or hospitalization: Withhold idelalisib; monitor at least weekly until resolved, then resume dose at 100 mg twice daily
• Life-threatening: Permanently discontinue

Neutropenia

• ANC 1 to less than 1.5 Gi/L: Maintain dose
• ANC 0.5 to less than 1 Gi/L: Maintain dose; monitor ANC at least weekly
• ANC less than 0.5 Gi/L: Withhold idelalisib; monitor ANC at least weekly until ANC ≥0.5 Gi/L, then resume at 100 mg twice daily

Thrombocytopenia

• Platelets 50 to less than 75 Gi/L: Maintain dose
• Platelets 25 to less than 5 Gi/L: Maintain dose; monitor platelets at least weekly
• Platelets less than 25 Gi/L: Withhold idelalisib; monitor platelets at least weekly until platelets 25 Gi/L or greater, then resume at 100 mg twice daily

Infections

• Evidence of CMV infection or viremia
  • Interrupt idelalisib in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved
  • If idelalisib is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly
• Grade 3 or higher sepsis or pneumonia
  • Interrupt idelalisib until infection has resolved
  • Interrupt idelalisib in patients with suspected PJP infection of any grade
  • Permanently discontinue idelalisib if PJP infection is confirmed
• Other severe or life-threatening toxicities

Evidence of PJP infection

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

Dosing Considerations

• Traditional (full) FDA approval for chronic lymphocytic leukemia (CLL)
• Accelerated approval for relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL)
• FDA accelerated approval program: Allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug affects a surrogate endpoint reasonably likely to predict clinical benefit to patients; this program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials
• Safety and efficacy not established for pediatric patients
• Geriatric patients: See Adult Dosing
  • No major differences in effectiveness were observed
  • Indolent non-Hodgkin lymphoma: Older patients (65 years and older) had a higher incidence of discontinuation due to an adverse reaction (28% vs 20%), higher incidence of serious adverse reactions (64% vs 37%), and a higher incidence of death (11% vs 5%)
  • CLL: Older patients (65 years and older) had a higher incidence of discontinuation due to an adverse reaction (11% vs 5%), higher incidence of serious adverse reactions (51% vs 43%), and higher incidence of death (3% vs 0%)

Limitation of use

• Not indicated or recommended for first-line treatment of any patients with CLL, FL, or SLL
• Not indicated or recommended in combination with bendamustine and/or rituximab for the treatment of FL

Side effects of Idelalisib may include:

• Decreased ANC, Grade 3-4
• Fever
• Low white blood cells (neutropenia), Grade 3 or 4
• Nausea
• Pneumonia
• Chills
• Diarrhea or colitis
• Increased lymphocyte count, Grade 3-4
• Rash
• Vomiting
• Hypoglycemia, any grade

Less common side effects of idelalisib (with rituximab for CLL) include:

• Headache
• Decreased lymphocyte count, Grade 3-4
• ALT increased, Grade 3-
• Sinusitis
• Sepsis
• Pain
• Joint pain
• GERD
• Inflammation of the mouth and lips
• Bronchitis
• AST increased, Grade 3-4

Common side effects of idelalisib (monotherapy for indolent non-Hodgkin lymphoma) include:

• Pneumonia, Grade 3 or greater
• Diarrhea, Grade 3 or greater
• ANC decreased, Grade 3-4
• ALT increased, Grade 3-4

Serious side effects of idelalisib include:

• Liver toxicity, fatal/serious

Postmarketing side effects of idelalisib reported include:

• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Severe interactions of idelalisib include:
  • alfuzosin
  • cisapride
  • cobimetinib
  • conivaptan
  • dihydroergotamine
  • dihydroergotamine intranasal
  • eliglustat
  • flibanserin
  • ivabradine
  • lovastatin
  • lurasidone
  • naloxegol
  • simvastatin
  • venetoclax
• Idelalisib has serious interactions with at least 274 different drugs.
• Idelalisib has moderate interactions with at least 49 different drugs.
• Mild interactions of idelalisib include:
  • ixazomib

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains idelalisib. Do not take Zydelig if you are allergic to idelalisib or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Black Box Warnings

• Fatal and/or serious hepatotoxicity occurred in 16-18% of treated patients; monitor hepatic function before and during treatment; interrupt and then reduce or discontinue as recommended
• Fatal and/or serious diarrhea, or colitis occurred in 14-20% of treated patients; monitor before and during treatment; interrupt and then reduce or discontinue idelalisib if symptoms/laboratory evidence appears
• Fatal and serious pneumonitis reported in 4% of treated patients; monitor for pulmonary symptoms and bilateral interstitial infiltrates; interrupt or discontinue idelalisib if pneumonitis suspected
• Fatal and/or serious infections occurred in 21-48% of treated patients; monitor for signs and symptoms of an infection; interrupt if the infection is suspected
• Fatal and serious intestinal perforation reported; discontinue if intestinal perforation is suspected

Contraindications

• History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Idelalisib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Idelalisib?"

Cautions

• Fatal and/or serious hepatotoxicity reported
• Avoid concurrent use with other drugs that may cause hepatotoxicity
• Severe diarrhea or colitis reported
• Fatal and serious pneumonitis reported; evaluate patients with pulmonary symptoms (e.g., cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic examination, or oxygen saturation decline of greater than 5%); if symptomatic pneumonitis or organizing pneumonia is diagnosed, initiate appropriate treatment with corticosteroids and permanently discontinue therapy
• Fatal and/or serious infections occurred in 21% of patients treated with monotherapy and 36% of patients treated in combination trials; the most common infections were pneumonia, sepsis, and febrile neutropenia; monitor for signs and symptoms of infection and interrupt for Grade 3 or higher infection; serious or fatal Pneumocystis jirovecii pneumonia (PJP) or cytomegalovirus (CMV) occurred in less than 1% of patients treated; regular clinical and laboratory monitoring for CMV infection is recommended in patients with a history of CMV infection or positive CMV serology at start of treatment
• Fatal and serious intestinal perforation reported; advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting
• Severe cutaneous reactions occurred in clinical trials, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS); other severe or life-threatening (Grade 3 or higher) cutaneous reactions reported include dermatitis, exfoliative rash, erythematous rash, generalized rash, macular rash, maculopapular rash, papular rash, pruritic rash, and skin disorder
• Serious allergic reactions, including anaphylaxis, reported; discontinue permanently if allergic reaction occurs
• Neutropenia requiring treatment (Grade 3 or 4) reported; monitor blood counts at least every 2 weeks for first 3 months of treatment and at least weekly if neutrophil count less than 1 Gi/L
• May cause fetal harm when administered to pregnant women

Drug interactions overview

• Idelalisib is predominantly metabolized by CYP3A; avoid coadministration with strong CYP3A inducers
• Strong CYP3A inhibitors are known to increase idelalisib AUC; monitor for signs of idelalisib toxicity (see Dosage Modifications)
• Idelalisib is a strong CYP3A inhibitor; avoid coadministration with CYP3A substrates

Pregnancy and Lactation

• There are no available data in pregnant women to inform the drug-associated risk of the use of idelalisib during pregnancy. In animal reproduction studies, administration of idelalisib to pregnant rats during organogenesis resulted in decreased fetal weight and congenital malformations in rats at maternal exposures (AUC) 12 times those reported in patients at the recommended dose of 150 mg twice daily.
• Females of reproductive potential should have a pregnancy test before starting treatment.
• Contraception
  • Females
    • Based on animal studies, idelalisib can cause fetal harm when administered to a pregnant woman
    • Females of reproductive potential are advised to use effective contraception during treatment with idelalisib and for at least 1 month after the last dose
  • Males
    • Based on findings in animal reproduction studies, male patients with female partners of reproductive potential are advised to use effective contraception during treatment and for 3 months after the last dose
• No data are available regarding the presence of idelalisib or its metabolites in human milk or its effects on the breastfed child or milk production. Owing to the potential for serious adverse reactions from idelalisib in a breastfed child, lactating women are advised not to breastfeed while taking idelalisib and for at least 1 month after the last dose.