Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 29 June 2018

Indication(s)

1 INDICATIONS AND USAGE Zydelig is a kinase inhibitor indicated for the treatment of patients with: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. (1.1) Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies. (1.2) Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies. (1.3) Limitation of use: Zydelig is not indicated and is not recommended for first-line treatment of any patient. (1.1, 1.2, 1.3) Zydelig is not indicated and is not recommended in combination with bendamustine and/or rituximab for the treatment of FL. (1.2) Accelerated approval was granted for FL and SLL based on overall response rate. Improvement in patient survival or disease related symptoms has not been established. Continued approval for these indications may be contingent upon verification of clinical benefit in confirmatory trials. 1.1 Relapsed Chronic Lymphocytic Leukemia Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Limitation of Use Zydelig is not indicated and is not recommended for first line treatment of patients with CLL. 1.2 Relapsed Follicular B-cell non-Hodgkin Lymphoma Zydelig is indicated for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on Overall Response Rate [see Clinical Studies (14.2)]. An improvement in patient survival or disease related symptoms has not been established. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. Limitation of Use Zydelig is not indicated and is not recommended for first line treatment of patients with FL. Zydelig is not indicated and is not recommended in combination with bendamustine and/or rituximab for the treatment of FL. 1.3 Relapsed Small Lymphocytic Lymphoma Zydelig is indicated for the treatment of patients with relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on Overall Response Rate [see Clinical Studies (14.3)]. An improvement in patient survival or disease related symptoms has not been established. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. Limitation of Use Zydelig is not indicated and is not recommended for first line treatment of patients with SLL.

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Advisory information

contraindications
4 CONTRAINDICATIONS History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis [see Warnings and Precautions (5.6, 5.7)] . History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis. (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions have been associated with Zydelig in clinical trials and are discussed in greater detail in other sections of the prescribing information. Hepatotoxicity [see Warnings and Precautions (5.1)] Severe Diarrhea or Colitis [see Warnings and Precautions (5.2)] Pneumonitis [see Warnings and Precautions (5.3)] Infections [see Warnings and Precautions (5.4)] Intestinal Perforation [see Warnings and Precautions (5.5)] Severe Cutaneous Reactions [see Warnings and Precautions (5.6)] Anaphylaxis [see Warnings and Precautions (5.7)] Neutropenia [see Warnings and Precautions (5.8)] The most common adverse reactions (incidence ≥20%) in patients treated with Zydelig in the monotherapy trial are diarrhea, fatigue, nausea, cough, pyrexia, abdominal pain, pneumonia, and rash. (6.1) The most common adverse reactions (incidence ≥30%) in patients treated with Zydelig in combination trials are diarrhea, pneumonia, pyrexia, fatigue, rash, cough, and nausea. (6.1) Common laboratory abnormalities include neutropenia, ALT elevations and AST elevations. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Summary of Clinical Trials in Chronic Lymphocytic Leukemia The safety data reflect exposure to Zydelig from two randomized, double-blind clinical trials (Studies 312-0116 and 312-0115) in 634 patients with relapsed CLL [see Clinical Studies (14.1)] and one randomized, open-label trial in 259 patients with relapsed CLL (Study 312-0119). Zydelig with Rituximab (Study 312-0116; NCT01539512) Patients with relapsed CLL received up to 8 doses of rituximab (R) with or without Zydelig 150 mg twice daily. The median duration of exposure to Zydelig was 8 months. Serious adverse reactions were reported in 65 (59%) patients treated with Zydelig + R The most frequent serious adverse reactions reported for patients treated with Zydelig + R were pneumonia (23%), diarrhea (10%), pyrexia (9%), sepsis (8%), and febrile neutropenia (5%). Adverse reactions that led to discontinuation of Zydelig occurred in 19 (17%) patients. The most common adverse reactions that led to treatment discontinuations were hepatotoxicity and diarrhea/colitis. Forty-two (38%) patients had dose interruptions and sixteen (15%) patients had dose reductions due to adverse reactions or laboratory abnormalities. The most common reasons for dose interruptions or reductions were pneumonia, diarrhea or colitis, rash, and elevated transaminases. Table 2 and Table 3 summarize common adverse reactions and laboratory abnormalities reported for Zydelig + R and placebo + R arms. Table 2 Adverse Reactions Reported in ≥5% of Patients with CLL and Occurred at ≥2% Higher Incidence in Patients Receiving Zydelig in Study 312-0116 Zydelig + R N=110 (%) Placebo + R N=108 (%) Adverse Reaction Any Grade Grade ≥3 Any Grade Grade ≥3 General disorders and administration site conditions pyrexia 44 (40) 3 (3) 20 (19) 1 (1) chills 27 (25) 2 (2) 17 (16) 0 pain 8 (7) 0 1 (1) 0 Gastrointestinal disorders diarrhea Diarrhea includes the following preferred terms: diarrhea, colitis. 35 (32) 12 (11) 20 (19) 0 nausea 30 (27) 1 (1) 25 (23) 0 abdominal pain Abdominal pain includes the following preferred terms: abdominal pain, abdominal pain upper, abdominal pain lower. 20 (18) 1 (1) 17 (16) 2 (2) vomiting 17 (15) 0 9 (8) 0 gastroesophageal reflux disease 11 (10) 1 (1) 0 0 stomatitis 7 (6) 2 (2) 1 (1) 0 Respiratory, thoracic, and mediastinal disorders pneumonia Pneumonia includes the terms: pneumonia, pneumonitis, lung infection, lung infiltration, pneumocystis jiroveci pneumonia, pneumonia legionella, lung infection pseudomonal, pneumonia fungal, respiratory tract infection, lower respiratory tract infection, and lower respiratory tract infection bacterial. 33 (30) 23 (21) 20 (19) 14 (13) Skin and subcutaneous tissue disorders rash Rash includes the following preferred terms: dermatitis exfoliative, drug eruption, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, rash morbilliform, and exfoliative rash. 27 (25) 4 (4) 7 (6) 1 (1) Metabolism and Nutrition Disorders decreased appetite 18 (16) 2 (2) 12 (11) 2 (2) dehydration 7 (6) 3 (3) 0 0 Infections and infestations sepsis Sepsis includes the terms: sepsis, septic shock, neutropenic sepsis, and sepsis syndrome 10 (9) 10 (9) 4 (4) 4 (4) sinusitis 9 (8) 0 6 (6) 0 urinary tract infection 9 (8) 1 (1) 4 (4) 2 (2) bronchitis 8 (7) 1 (1) 5 (5) 1 (1) oral herpes 6 (5) 1 (1) 3 (3) 0 Psychiatric disorders insomnia 10 (9) 0 7 (6) 0 Musculoskeletal and connective tissue disorders arthralgia 9 (8) 1 (1) 4 (4) 0 Nervous system disorders lethargy 6 (5) 0 2 (2) 0 Table 3 Hematologic and Hepatic Laboratory Abnormalities Reported in ≥10% of Patients with CLL and Occurred at ≥5% Higher Incidence in Patients Receiving Zydelig in Study 312-0116 Zydelig + R N=110 (%) Placebo + R N=108 (%) Laboratory Parameter Any Grade Grade 3–4 Any Grade Grade 3–4 Hematology abnormalities neutropenia 71 (65) 46 (42) 61 (56) 33 (31) leukopenia 34 (31) 9 (8) 25 (23) 9 (8) lymphocytopenia 23 (21) 11 (10) 13 (12) 4 (4) Serum chemistry abnormalities ALT increased 43 (39) 10 (9) 13 (12) 1 (1) AST increased 31 (28) 6 (5) 16 (15) 0 After closure of Study 312-0116, 71 patients continued treatment with Zydelig on an extension study (Study 312-0117; NCT01539291). The median duration of exposure was 18 months. Serious adverse reactions occurred in 48 (68%) patients. The most frequent serious adverse reactions reported were pneumonia (30%), diarrhea (15%), and pyrexia (11%). The most frequent adverse reactions were pneumonia (51%), pyrexia (46%), and cough (45%). The most frequent Grade 3 or greater adverse reactions were pneumonia (30%), diarrhea (15%), and sepsis (10%). Zydelig with Ofatumumab (Study 312-0119; NCT01659021) In Study 312-0119, 259 patients with relapsed CLL received up to 12 doses of ofatumumab with or without Zydelig 150 mg twice daily. The median duration of exposure to Zydelig was 13.9 months. Serious adverse reactions were reported in 133 (77%) patients treated with Zydelig + ofatumumab. The most frequent serious adverse reactions reported were pneumonia (14%), pyrexia (13%), and diarrhea (12%). Adverse reactions that led to discontinuation of Zydelig occurred in 71 (41%) patients. One hundred and ten (64%) patients had dose interruptions and 42 (24%) patients had dose reductions due to adverse reactions or laboratory abnormalities. The most common reasons for dose discontinuations, reductions, or interruptions were diarrhea and colitis. The most common adverse reactions were diarrhea (55%), pyrexia (38%), nausea (34%), and fatigue (34%). Zydelig with Bendamustine and Rituximab (Study 312-0115; NCT01569295) In Study 312-0115, patients with relapsed CLL received up to 6 cycles of bendamustine and rituximab (BR) with or without Zydelig 150 mg twice daily. The median duration of exposure to Zydelig was 18.2 months. Serious adverse reactions were reported in 147 (71%) patients treated with Zydelig + BR. The most frequent serious adverse reactions reported for patients treated with Zydelig + BR were febrile neutropenia (21%), pneumonia (17%), pyrexia (12%), and diarrhea (6%). Adverse reactions that led to discontinuation of Zydelig occurred in 68 (33%) patients. The most common adverse reactions that led to treatment discontinuations were pneumonia, diarrhea, and pyrexia. One hundred twenty-two (59%) patients treated with Zydelig + BR had dose interruptions and 34 (16%) patients had dose reductions due to adverse reactions. The most common reasons for dose interruptions or reductions were increased ALT and diarrhea. The most common adverse reactions were neutropenia (64%), pyrexia (43%), and diarrhea (41%). Summary of Clinical Trials in Indolent Non-Hodgkin Lymphoma The safety data reflect exposure to Zydelig from three open-label clinical trials (Studies 101-09 (NCT01282424), 101-02 (NCT00710528), and 101-10 (NCT01306643) in 146 patients with indolent non-Hodgkin lymphoma (iNHL) treated with Zydelig 150 mg twice daily [see Clinical Studies (14.2, 14.3)]. The median duration of exposure was 6.1 months (range 0.3 to 26.4 months). Serious adverse reactions were reported in 73 (50%) patients. The most frequent serious adverse reactions that occurred were pneumonia (15%), diarrhea (11%), and pyrexia (9%). Adverse reactions resulted in interruption or discontinuation for 78 (53%) patients. The most common reasons for interruption or discontinuations were diarrhea (11%), pneumonia (11%), and elevated transaminases (10%). Table 4 provides the adverse reactions occurring in at least 10% of patients receiving Zydelig monotherapy, and Table 5 provides the hematologic and hepatic laboratory abnormalities. Table 4 Adverse Reactions Reported in ≥ 10% of Patients with Indolent NHL Treated with Zydelig 150 mg BID Zydelig Monotherapy N=146 (%) Adverse Reaction Any Grade Grade ≥3 Gastrointestinal disorders diarrhea Diarrhea includes the following preferred terms: diarrhea, colitis, enterocolitis, and gastrointestinal inflammation. 68 (47) 20 (14) nausea 42 (29) 2 (1) abdominal pain Abdominal pain includes the following preferred terms: abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort. 38 (26) 3 (2) vomiting 22 (15) 2 (1) General disorders and administration site conditions fatigue 44 (30) 2 (1) pyrexia 41 (28) 3 (2) asthenia 17 (12) 3 (2) peripheral edema 15 (10) 3 (2) Respiratory, thoracic, and mediastinal disorders cough 42 (29) 1 (1) pneumonia Pneumonia includes the terms: pneumonia, pneumonitis, interstitial lung disease, lung infiltration, pneumonia aspiration, respiratory tract infection, atypical pneumonia, lung infection, pneumocystis jiroveci pneumonia, bronchopneumonia, pneumonia necrotizing, lower respiratory tract infection, pneumonia pneumococcal, pneumonia staphylococcal, pneumonia streptococcal, pneumonia cytomegaloviral, and respiratory syncytial virus infection. 37 (25) 23 (16) dyspnea 25 (17) 6 (4) Skin and subcutaneous disorders rash Rash includes the following preferred terms: dermatitis exfoliative, rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic, and exfoliative rash. 31 (21) 4 (3) night sweats 18 (12) 0 Metabolism and nutrition disorders decreased appetite 24 (16) 1 (1) Infections and infestations upper respiratory tract infection 18 (12) 0 Psychiatric disorders insomnia 17 (12) 0 Nervous system disorders headache 16 (11) 1 (1) Table 5 Hematologic and Hepatic Laboratory Abnormalities in Patients with Indolent non-Hodgkin Lymphoma Treated with Zydelig 150 mg BID Zydelig Monotherapy N=146 (%) Laboratory Abnormality Any Grade Grade 3 Grade 4 Grades were obtained per CTCAE version 4.03. Serum chemistry abnormalities ALT increased 73 (50) 20 (14) 7 (5) AST increased 60 (41) 12 (8) 6 (4) Hematology abnormalities neutrophils decreased 78 (53) 20 (14) 16 (11) hemoglobin decreased 41 (28) 3 (2) 0 platelets decreased 38 (26) 4 (3) 5 (3) Summary of Discontinued Clinical Trials in First-Line CLL and Early Line iNHL Safety data described below reflect exposure to Zydelig in three randomized, double-blind clinical trials (Studies 312-0123, 313-0124, and 313-0125) in patients with CLL and iNHL. In Study 312-0123 (NCT01980888), 311 patients with previously untreated CLL received up to 6 cycles of BR with or without Zydelig 150 mg twice daily. In Study 313-0124 (NCT01732913), 295 patients with previously treated iNHL received 8 doses of R with or without Zydelig 150 mg twice daily. Patients had a median of one prior therapy. In Study 313-0125 (NCT01732926), 475 patients with previously treated iNHL received up to 6 cycles of BR with or without Zydelig 150 mg twice daily. Patients had a median of two prior therapies. These three studies were terminated early due to a higher incidence of fatal and/or serious adverse reactions observed in patients treated with Zydelig in combination with R or BR. The most frequent serious adverse reactions were in the system organ classes of infections and infestations, blood and lymphatic system disorders, and gastrointestinal disorders. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Zydelig. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Disorders - Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Recommended starting dose: 150 mg orally, twice daily. (2.1) 2.1 Recommended Dosage The recommended maximum starting dose of Zydelig is 150 mg administered orally twice daily. Zydelig can be taken with or without food. Tablets should be swallowed whole. Continue treatment until disease progression or unacceptable toxicity. The optimal and safe dosing regimen for patients who receive treatment longer than several months is unknown. 2.2 Dose Modification See Table 1 for dose modification instructions for specific toxicities related to Zydelig. 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. Table 1 Dose Modifications for Toxicities Due to Zydelig Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal; CMV, cytomegalovirus; PCR: polymerase chain reaction; PJP: Pneumocystis jirovecii pneumonia Pneumonitis Any symptomatic pneumonitis Discontinue Zydelig in patients with any severity of symptomatic pneumonitis ALT/AST >3–5 × ULN >5–20 × ULN >20 × ULN Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. Withhold Zydelig. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume Zydelig at 100 mg BID. Discontinue Zydelig permanently. Bilirubin >1.5–3 × ULN >3–10 × ULN >10 × ULN Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. Withhold Zydelig. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume Zydelig at 100 mg BID. Discontinue Zydelig permanently. DiarrheaModerate diarrhea: increase of 4–6 stools per day over baseline; severe diarrhea: increase of ≥7 stools per day over baseline. Moderate diarrhea Severe diarrhea or hospitalization Life-threatening diarrhea Maintain Zydelig dose. Monitor at least weekly until resolved. Withhold Zydelig. Monitor at least weekly until resolved, then may resume Zydelig at 100 mg BID. Discontinue Zydelig permanently. Neutropenia ANC 1.0 to <1.5 Gi/L ANC 0.5 to <1.0 Gi/L ANC <0.5 Gi/L Maintain Zydelig dose. Maintain Zydelig dose. Monitor ANC at least weekly. Interrupt Zydelig. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then may resume Zydelig at 100 mg BID. Thrombocytopenia Platelets 50 to <75 Gi/L Platelets 25 to <50 Gi/L Platelets <25 Gi/L Maintain Zydelig dose. Maintain Zydelig dose. Monitor platelet counts at least weekly. Interrupt Zydelig. Monitor platelet count at least weekly. May resume Zydelig at 100 mg BID when platelets ≥25 Gi/L. Infections 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. Permanently discontinue Zydelig if PJP infection is confirmed. No dose modification is required for lymphocytosis, which has been observed in some patients taking Zydelig. This observed lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed. (8.2) 8.1 Pregnancy Risk Summary Based on findings in animal studies (see Data) and the mechanism of action [see Clinical Pharmacology (12.1)], Zydelig may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. 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 (see Data). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2–4% and of miscarriage is 15–20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In an embryo-fetal development study in rats, pregnant animals receiving oral doses of idelalisib during the period of organogenesis (implantation to closure of the hard palate), embryo-fetal toxicities were observed at the mid- and high-doses that also resulted in maternal toxicity, based on reductions in maternal body weight gain. Adverse findings at idelalisib doses ≥ 75 mg/kg/day included decreased fetal weights, external malformations (short tail), and skeletal variations (delayed ossification and/or unossification of the skull, vertebrae, and sternebrae). Additional findings were observed at 150 mg/kg/day dose of idelalisib and included urogenital blood loss, complete resorption, increased post-implantation loss, and malformations (vertebral agenesis with anury, hydrocephaly, and microphthalmia/anophthalmia). The dose of 75 and 150 mg/kg/day of idelalisib in rats resulted in exposures (AUC) of approximately 12 and 30 times, respectively, the human exposure at the recommended dose of 150 mg twice daily. 8.2 Lactation Risk Summary No data are available regarding the presence of idelalisib or its metabolites in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions from Zydelig in a breastfed child, advise lactating women not to breastfeed while taking Zydelig and for at least 1 month after the last dose. 8.3 Females and Males of Reproductive Potential Pregnancy Based on animal studies, Zydelig may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Females of reproductive potential should have a pregnancy test prior to starting treatment with Zydelig. Contraception Females Based on animal studies, Zydelig can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Zydelig and for at least 1 month after the last dose. Males Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of Zydelig [see Use in Specific Populations (8.1)]. 8.4 Pediatric Use Safety and effectiveness of Zydelig in children less than 18 years of age have not been established. 8.5 Geriatric Use In clinical trials of Zydelig in 615 patients with FL, SLL, and CLL, 327 (53%) patients were age 65 and older. No major differences in effectiveness were observed. When comparing patients 65 years of age or older to younger patients with indolent non-Hodgkin lymphoma, older patients had a higher incidence of discontinuation due to an adverse reaction (28% vs 20%), higher incidence of serious adverse reactions (64% vs 37%), and higher incidence of death (11% vs 5%). When comparing patients 65 years of age or older to younger patients with CLL, older patients had a higher incidence of discontinuation due to an adverse reaction (36% vs 28%), higher incidence of serious adverse reactions (73% vs 67%), and higher incidence of death (13% vs 9%). 8.6 Hepatic Impairment Dose adjustment is not recommended for patients with ALT or AST or bilirubin > upper limit of normal (ULN); however, limited safety and efficacy data are available for patients with baseline AST or ALT > 2.5 × ULN or bilirubin > 1.5 × ULN. Monitor patients with baseline hepatic impairment for signs of Zydelig toxicity [see Warnings and Precautions (5)]. Follow dose modifications for adverse reactions [see Dosage and Administration (2.2)].

Interactions

7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Additional monitoring required if alternative therapy is not available. (7.1) Strong CYP3A inducers: Avoid coadministration of strong CYP3A inducers. (7.1) CYP3A substrates: Avoid coadministration of sensitive CYP3A substrates. (7.2) 7.1 Effects of Other Drugs on Zydelig Table 6 Drug Interactions with Zydelig that affect Idelalisib Concentrations Strong CYP3A Inhibitors Clinical Impact Coadministration with strong CYP3A inhibitors may increase idelalisib concentrations [see Clinical Pharmacology (12.3)]. Increased idelalisib concentrations may increase the risk of exposure related adverse reactions. Prevention or Management Use other drugs that are not strong CYP3A inhibitors. If unable to use alternative drugs, monitor patients more frequently for Zydelig adverse reactions [see Warnings and Precautions (5)]. Strong CYP3A Inducers Clinical Impact Coadministration with strong CYP3A inducers may decrease idelalisib concentrations [see Clinical Pharmacology (12.3)]. Decreased idelalisib concentrations may reduce efficacy. Prevention or Management Avoid coadministration of Zydelig with strong CYP3A4 inducers. 7.2 Effects of Zydelig on Other Drugs The coadministration of Zydelig with a CYP3A substrate may increase the concentrations of this CYP3A substrate. Avoid coadministration of Zydelig with sensitive CYP3A substrates [see Clinical Pharmacology (12.3)].

More information

Category Value
Authorisation number NDA205858
Agency product number YG57I8T5M0
Orphan designation No
Product NDC 61958-1702,61958-1701
Date Last Revised 08-02-2018
Type HUMAN PRESCRIPTION DRUG
Storage and handling Store between 20–30 °C (68–86 °F) with excursions permitted 15–30 °C (59–86 °F). Dispense only in original container. Do not use if seal over bottle opening is broken or missing.
Marketing authorisation holder Gilead Sciences, Inc.
Warnings WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, INFECTIONS, and INTESTINAL PERFORATION Fatal and/or serious hepatotoxicity occurred in 16% to 18% 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 (2.2), Warnings and Precautions (5.1)]. Fatal and/or serious and severe diarrhea or colitis occurred in 14% to 20% 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 (2.2), Warnings and Precautions (5.2)]. Fatal and/or serious pneumonitis occurred in 4% of Zydelig-treated patients. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig as recommended [see Dosage and Administration (2.2), Warnings and Precautions (5.3)]. Fatal and/or serious infections occurred in 21% to 48% of Zydelig-treated patients. Monitor for signs and symptoms of infection. Interrupt Zydelig if infection is suspected [see Dosage and Administration (2.2), Warnings and Precautions (5.4)]. Fatal and serious intestinal perforation can occur in Zydelig-treated patients across clinical trials. Discontinue Zydelig for intestinal perforation [see Warnings and Precautions (5.5)]. WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, INFECTIONS, and INTESTINAL PERFORATION See full prescribing information for complete boxed warning. Fatal and/or serious hepatotoxicity occurred in 16% to 18% of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig. (5.1) Fatal and/or serious and severe diarrhea or colitis occurred in 14% to 20% of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig. (5.2) Fatal and/or serious pneumonitis occurred in 4% of Zydelig-treated patients. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig. (5.3) Fatal and/or serious infections occurred in 21% to 48% of Zydelig-treated patients. Monitor for signs and symptoms of infection. Interrupt Zydelig if infection is suspected. (5.4) Fatal and serious intestinal perforation can occur in Zydelig-treated patients across clinical trials. Discontinue Zydelig if intestinal perforation is suspected. (5.5)