Idelalisib

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Zydelig: 100 mg [contains fd&c yellow #6 aluminum lake]

Zydelig: 150 mg

Pharmacology

Mechanism of Action

Idelalisib is a potent small molecule inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3Kδ), which is highly expressed in malignant lymphoid B-cells. PI3Kδ inhibition results in apoptosis of malignant tumor cells. In addition, idelalisib inhibits several signaling pathways, including B-cell receptor, CXCR4 and CXCR5 signaling which may play important roles in CLL pathophysiology (Furman 2014).

Pharmacokinetics/Pharmacodynamics

Distribution

23 L

Metabolism

Hepatic; primarily via aldehyde oxidase and CYP3A (to major metabolite GS-563117); minor metabolism via UGT1A4

Excretion

Feces (78%); urine (14%)

Time to Peak

Median: 1.5 hours

Half-Life Elimination

8.2 hours

Protein Binding

≥84%

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Exposure increased 1.7-fold in patients with ALT or AST or bilirubin ≥ULN as compared with patients with normal liver function tests.

Use: Labeled Indications

Chronic lymphocytic leukemia: Treatment of relapsed chronic lymphocytic leukemia (CLL) (in combination with rituximab) when rituximab alone is appropriate therapy due to other comorbidities

Follicular B-cell non-Hodgkin lymphoma: Treatment of relapsed follicular B-cell non-Hodgkin lymphoma (NHL) after at least 2 prior systemic therapies

Small lymphocytic lymphoma: Treatment of relapsed small lymphocytic lymphoma (SLL) after at least 2 prior systemic therapies

Limitations of use: Idelalisib is not indicated or recommended for first-line treatment of CLL, follicular B-cell NHL, or SLL. Idelalisib is not indicated and is not recommended in combination with bendamustine and/or rituximab for the treatment of follicular NHL.

Contraindications

Serious hypersensitivity reactions (including anaphylaxis and toxic epidermal necrolysis) to idelalisib or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Use in first-line chronic lymphocytic leukemia and early-line indolent non-Hodgkin lymphoma outside of a clinical trial

Dosage and Administration

Dosing: Adult

Note: The maximum recommended starting dose is 150 mg twice daily. Optimal duration and safety of therapy beyond several months is currently unknown.

Chronic lymphocytic leukemia, relapsed: Oral: 150 mg twice daily (in combination with rituximab); continue until disease progression or unacceptable toxicity (Furman 2014)

Follicular B-cell non-Hodgkin lymphoma, relapsed: Oral: 150 mg twice daily; continue until disease progression or unacceptable toxicity (Gopal 2014)

Small lymphocytic lymphoma, relapsed: Oral: 150 mg twice daily; continue until disease progression or unacceptable toxicity (Gopal 2014)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Anaphylaxis or other serious allergic reactions: Permanently discontinue.

Dermatologic toxicity:

Severe cutaneous reactions: Discontinue.

Suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): Interrupt therapy; discontinue permanently if SJS or TEN are confirmed.

Gastrointestinal toxicity:

Moderate diarrhea (increase of 4 to 6 stools/day over baseline): Continue current dose; monitor at least weekly until resolved.

Severe diarrhea (increase of ≥7 stools/day over baseline) or hospitalization: Temporarily interrupt therapy; monitor at least weekly until resolved, then may reinitiate therapy at 100 mg twice daily.

Life-threatening diarrhea: Discontinue permanently.

Hematologic toxicity:

Neutropenia:

ANC 1,000 to <1,500 cells/mm³: Continue current dose.

ANC 500 to <1,000 cells/mm³: Continue current dose; monitor blood counts at least weekly.

ANC <500 cells/mm³: Temporarily interrupt therapy; monitor blood counts at least weekly until ANC ≥500 cells/mm³, then may reinitiate therapy at 100 mg twice daily.

Thrombocytopenia:

Platelets 50,000 to <75,000 cells/mm³: Continue current dose.

Platelets 25,000 to <50,000 cells/mm³: Continue current dose; monitor platelet counts at least weekly.

Platelets <25,000 cells/mm³: Temporarily interrupt therapy; monitor platelet counts at least weekly, may reinitiate therapy at 100 mg twice daily when platelets recover to ≥25,000 cells/mm³.

Lymphocytosis: Dosage modification is not required.

Infection:

Sepsis, pneumonia, or other infection (grade 3 or higher): Interrupt therapy until infection has resolved.

Cytomegalovirus (CMV) infection or viremia: Interrupt therapy for evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until viremia has resolved. If idelalisib is reinitiated, monitor for CMV reactivation by PCR or antigen test at least monthly.

Pneumocystis jirovecii pneumonia (PCP) infection: Interrupt therapy for suspected PCP infection of any grade; permanently discontinue if PCP infection is confirmed.

Pulmonary toxicity: If pneumonitis is suspected, interrupt therapy and evaluate; permanently discontinue for symptomatic pneumonitis of any severity thought to be associated with therapy (may also require corticosteroids).

Other toxicity (not listed above): If severe or life-threatening toxicities occur, interrupt therapy until toxicity is resolved. If the decision is made to resume therapy, reduce the dose to 100 mg twice daily. Discontinue permanently if severe or life-threatening toxicities recur upon rechallenge.

Administration

Oral: May be administered with or without food. Swallow tablets whole.

Missed doses: May administer a missed dose if within 6 hours of usual dosing time. If >6 hours, skip the missed dose and resume therapy with the next scheduled dose.

Storage

Store at 20°C to 30°C (68°F to 86°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense in the original container.

Drug Interactions

Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. Avoid combination

Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Avoid combination

Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Avoid combination

Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Consider therapy modification

Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Monitor therapy

Apixaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Avoid combination

Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination

Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Avoid combination

Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Avoid combination

Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. Avoid combination

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bedaquiline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline. Exceptions discussed in separate monographs. Consider therapy modification

Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Monitor therapy

Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Monitor therapy

Bictegravir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. Monitor therapy

Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Avoid combination

Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Bosentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Monitor therapy

Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Avoid combination

Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Monitor therapy

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Monitor therapy

Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Avoid combination

Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification

Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Monitor therapy

Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Monitor therapy

Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Avoid combination

Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). Monitor therapy

Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Idelalisib. Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Idelalisib. Monitor therapy

CYP3A4 Substrates (High risk with Inhibitors): Idelalisib may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Avoid combination

Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Delamanid: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Exceptions discussed separately. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Monitor therapy

Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Dofetilide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. Monitor therapy

Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination

Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy

Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination

Drospirenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors. Consider therapy modification

Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination

Enfortumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Avoid combination

Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. Monitor therapy

Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Avoid combination

Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Avoid combination

Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Avoid combination

Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Avoid combination

Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Monitor therapy

Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. Monitor therapy

Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination

Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Avoid combination

Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Consider therapy modification

Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Monitor therapy

Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. Avoid combination

Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Consider therapy modification

Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Avoid combination

Lacosamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Monitor therapy

Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Avoid combination

Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. Avoid combination

Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Avoid combination

Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Monitor therapy

Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Avoid combination

Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Avoid combination

Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Avoid combination

Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Monitor therapy

Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid combination

Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Avoid combination

MedroxyPROGESTERone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. Monitor therapy

Meperidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Avoid combination

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Avoid combination

NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Avoid combination

Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy

Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Monitor therapy

Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Avoid combination

Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy

Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination

Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Monitor therapy

PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. Consider therapy modification

Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. Monitor therapy

PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Monitor therapy

PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Avoid combination

Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy

Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Avoid combination

Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Avoid combination

Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Avoid combination

Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. Monitor therapy

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. Monitor therapy

Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Monitor therapy

Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. Avoid combination

Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sibutramine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. Monitor therapy

Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Avoid combination

Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Avoid combination

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Avoid combination

SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Monitor therapy

St John's Wort: May decrease the serum concentration of Idelalisib. Avoid combination

Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Avoid combination

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Avoid combination

Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Monitor therapy

Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. Avoid combination

Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Monitor therapy

Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. Consider therapy modification

Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Avoid combination

Toremifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Exceptions are discussed in separate monograph. Consider therapy modification

Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Avoid combination

TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Avoid combination

Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. Avoid combination

Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Avoid combination

Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. Avoid combination

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Vilanterol: May increase the serum concentration of CYP3A4 Inhibitors (Strong). Monitor therapy

Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Monitor therapy

Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Avoid combination

Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Avoid combination

Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Monitor therapy

Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. Consider therapy modification

Adverse Reactions

As reported with monotherapy.

>10%:

Central nervous system: Fatigue (30%), insomnia (12%), headache (11%)

Dermatologic: Skin rash (21%), night sweats (12%)

Gastrointestinal: Diarrhea (47%), nausea (29%), abdominal pain (26%), decreased appetite (16%), vomiting (15%)

Hematologic & oncologic: Decreased hemoglobin (28%; grade 3: 2%), decreased platelet count (26%; grade 3: 3%; grade 4: 3%), neutropenia (25%; grades 3/4)

Hepatic: Increased serum ALT (50%), increased serum AST (41%), severe hepatotoxicity (18%)

Infection: Severe infection (21%; including sepsis, febrile neutropenia)

Neuromuscular & skeletal: Weakness (12%)

Respiratory: Cough (29%), pneumonia (15% to 25%), dyspnea (17%), upper respiratory tract infection (12%)

Miscellaneous: Fever (28%)

1% to 10%:

Cardiovascular: Peripheral edema (10%)

Respiratory: Pneumonitis (4%)

<1%, postmarketing, and/or case reports: Anaphylaxis, cytomegalovirus disease, erythematous rash, exfoliative dermatitis, hypersensitivity reaction, intestinal perforation, macular eruption, maculopapular rash, papular rash, pneumonia due to pneumocystic carinii, progressive multifocal leukoencephalopathy (Raisch 2016), pruritic rash, Stevens-Johnson syndrome, toxic epidermal necrolysis

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Grade 3 or 4 neutropenia occurs commonly; thrombocytopenia and anemia (any grade) have also been reported. Monitor blood counts at least every 2 weeks for the first 6 months and at least weekly in patients with neutropenia (ANC <1,000/mm³). May require treatment interruption and dosage reduction. Lymphocytosis does not require dosage modification.
• Dermatologic toxicity: Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (some fatal). Severe and/or life-threatening cutaneous/mucocutaneous reactions (grade 3 or higher), including exfoliative dermatitis, rash (generalized, erythematous, maculopapular, papular, pruritic, exfoliative), and skin disorder, have been observed. Monitor closely for dermatologic toxicity and discontinue for severe reactions.
• Gastrointestinal events: [US Boxed Warning]: Serious and fatal intestinal perforation may occur; discontinue idelalisib if perforation develops. In some patients, perforation was preceded by moderate to severe diarrhea. Diarrhea and colitis have been reported with single-agent idelalisib, when used in combination with rituximab, and with unapproved combination therapies. Monitor closely for new or worsening abdominal pain, chills, fever, nausea, or vomiting.
• Gastrointestinal perforation: [US Boxed Warning]: Serious and fatal intestinal perforation may occur; discontinue idelalisib if perforation develops. In some patients, perforation was preceded by moderate to severe diarrhea. Diarrhea and colitis have been reported with single-agent idelalisib, when used in combination with rituximab, and with unapproved combination therapies. Monitor closely for new or worsening abdominal pain, chills, fever, nausea, or vomiting.
• Hepatotoxicity: [US Boxed Warning]: Serious hepatotoxicity (some fatal) has been observed. Monitor hepatic function at baseline and during therapy. May require treatment interruption, dosage reduction, and/or discontinuation. Hepatotoxicity has been reported with single-agent idelalisib, when used in combination with rituximab, and with unapproved combination therapies. ALT/AST elevations >5 times ULN have occurred and were generally observed during the first 12 weeks of therapy; transaminase elevations were reversible upon therapy interruption. Hepatotoxicity may recur upon rechallenge, even at a reduced dose; discontinue for recurrent hepatotoxicity. Avoid concomitant use with other hepatotoxic agents. Monitor ALT/AST at baseline and every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1 to 3 months thereafter, or as clinically necessary. Increase monitoring to weekly if ALT or AST >3 times ULN until resolved. Interrupt therapy if ALT/AST >5 times ULN; monitor LFTs weekly until resolved.
• Hypersensitivity reactions: Serious allergic/hypersensitivity reactions, including anaphylaxis, have been reported. Discontinue permanently for serious reactions and manage appropriately.
• Infections: [US Boxed Warning]: Fatal and/or serious infection has occurred in idelalisib-treated patients. Monitor for signs and symptoms of infection. Interrupt idelalisib if infection is suspected or for grade 3 or higher infection. Infections have been reported with single-agent idelalisib, when used in combination with rituximab, and with unapproved combination therapies. Commonly reported infections include pneumonia, sepsis, and febrile neutropenia. Infections should be treated prior to initiating treatment with idelalisib. Serious cases (some fatal) of Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) have been reported rarely. Provide PCP prophylaxis throughout idelalisib treatment (and after discontinuation if infection risk persists). Interrupt treatment if PCP infection of any grade is suspected; permanently discontinue if PCP infection is confirmed. Regular monitoring for CMV infection (clinical and laboratory) is recommended in patients with a history of CMV infection or positive CMV serology at the start of idelalisib treatment. Interrupt idelalisib for positive CMV PCR or antigen test until the infection has resolved. If idelalisib is reinitiated, monitor for CMV reactivation by PCR or antigen test at least monthly.
• Pneumonitis: [US Boxed Warning]: Serious and/or fatal pneumonitis may occur. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. May require therapy interruption or discontinuation. Clinical manifestations include interstitial infiltrates and organizing pneumonia. The time to onset of symptoms ranged from less than 1 month to 15 months after therapy initiation. If symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates, or an oxygen saturation decrease of more than 5% occur, interrupt therapy and promptly evaluate. If symptomatic pneumonitis or organizing pneumonia is diagnosed, initiate appropriate corticosteroids and permanently discontinue idelalisib.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Complete blood counts with differential at least every 2 weeks for the first 6 months, and at least weekly in patients with neutropenia (ANC <1,000/mm³ ), or as clinically necessary; liver function tests at baseline and every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1 to 3 months thereafter, or as clinically necessary; pregnancy test (prior to treatment initiation in females of reproductive potential); monitor for infections (including sepsis, pneumonia, PCP, and CMV); monitor for signs/symptoms of diarrhea/colitis, intestinal perforation, pneumonitis, dermatologic toxicity, and hypersensitivity reactions. Monitor adherence.

Pregnancy

Pregnancy Considerations

Based on findings in animal reproduction studies and the mechanism of action, idelalisib may cause fetal harm if administered during pregnancy. Verify pregnancy status in females of reproductive potential prior to initiating treatment with idelalisib. Females of reproductive potential should use effective contraception during therapy and for at least 1 month after the final idelalisib dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the final idelalisib dose.

Patient Education

What is this drug used for?

• It is used to treat a type of leukemia.
• It is used to treat a type of lymphoma.

Frequently reported side effects of this drug

• Headache
• Heartburn
• Joint pain
• Lack of appetite
• Loss of strength and energy
• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Bowel problems like black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; or diarrhea
• Severe pulmonary disorder like lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse
• Infection
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Severe diarrhea
• Increase in bowel movements by six or more in a day
• Dry skin
• Dry mouth
• Dry eyes
• Increased thirst
• Fast heartbeat
• Dizziness
• Fast breathing
• Confusion
• Mouth sores
• Night sweats
• Swelling of arms or legs
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.