Drug Safety-related Labeling Changes (SrLC)

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ZYDELIG (NDA-205858)

(IDELALISIB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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10/19/2020 (SUPPL-14)

Approved Drug Label (PDF)

4 Contraindications


(Additions underlined)

Zydelig is contraindicated in patients with a history of serious hypersensitivity reactions to idelalisib, including anaphylaxis, or patients with a history of toxic epidermal necrolysis with any drug [see Warnings and Precautions (5.6, 5.7)].


5 Warnings and Precautions

5.6 Severe Cutaneous Reactions


(Additions underlined)

Fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have occurred in patients treated with Zydelig. Cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have also occurred. Zydelig is contraindicated in patients with a history of toxic epidermal necrolysis [see Contraindications (4)]. If SJS, TEN, or DRESS is suspected, interrupt Zydelig until the etiology of the reaction has been determined. If SJS, TEN, or DRESS is confirmed, permanently discontinue Zydelig [see Dosage and Administration (2.2)].

Other severe or life-threatening (Grade greater than or equal to3) cutaneous reactions, including dermatitis exfoliative, rash, rash erythematous, rash generalized, rash macular, rash maculo- papular, rash papular, rash pruritic, exfoliative rash, and skin disorder, have been reported in patients treated with Zydelig. Monitor patients for the development of other severe or life-threatening cutaneous reactions and permanently discontinue Zydelig [see Dosage and Administration (2.2)].


5.7 Hypersensitivity Reactions


(Additions underlined)

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients on Zydelig. Zydelig is contraindicated in patients with a history of serious hypersensitivity reactions to idelalisib, including anaphylaxis [see Contraindications (4)]. In patients who develop serious hypersensitivity reactions, permanently discontinue Zydelig [see Dosage and Administration (2.2)] and institute appropriate supportive measures.


5.8 Neutropenia


(Additions underlined)

Grade 3 or 4 neutropenia occurred in 25% of patients treated with Zydelig monotherapy and 58% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies. Monitor blood counts at least every 2 weeks for the first 6 months of therapy, and at least weekly in patients while neutrophil counts are less than 1.0 Gi/L. Interrupt Zydelig until resolution and resume at reduced dose [see Dosage and Administration (2.2)].


6 Adverse Reactions

6.2 Postmarketing Experience


(Additions underlined)

Skin and Subcutaneous Disorders - Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS).


17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE


(Additions underlined)

Do not take Zydelig if you:

·         have had a serious allergic reaction to idelalisib.

·         have had a severe skin reaction called toxic epidermal necrolysis (TEN) to any drug.


PATIENT COUNSELING INFORMATION


(Additions underlined)

Advise males with female partners of reproductive potential to use effective contraception during treatment with Zydelig and for 3 months after receiving the last dose [see Use in Specific Populations (8.3)].


10/10/2018 (SUPPL-13)

Approved Drug Label (PDF)

7 Drug Interactions

7.1 Effects of Other Drugs on Zydelig

(additions underlined)

Table 6 lists the potential effects of the coadministration of strong CYP3A modulators on Zydelig.

Table 6         Drug Interactions with Zydelig that affect Idelalisib Concentrations

(please refer to label to view Table 6)

01/26/2018 (SUPPL-9)

Approved Drug Label (PDF)

Boxed Warning

(Additions and/or revisions are underlined)

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…

Fatal and/or serious and severe diarrhea or colitis occurred in 14% to 20% of Zydelig-treated patients…

Fatal and/or serious infections occurred in 21% to 48% of Zydelig-treated patients…

5 Warnings and Precautions

5.1 Hepatotoxicity

(Additions and/or revisions are underlined)

Fatal and/or serious hepatotoxicity occurred in 18% of patients treated with Zydelig monotherapy and 16% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies

5.2 Severe Diarrhea or Colitis

(Additions and/or revisions are underlined)

Severe diarrhea or colitis (Grade 3 or higher) occurred in 14% of patients treated with Zydelig monotherapy and 20% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies

5.3 Pneumonitis

(Additions and/or revisions are underlined)

Fatal and serious pneumonitis occurred in patients treated with Zydelig. Clinical manifestations included interstitial infiltrates and organizing pneumonia. In randomized clinical trials of combination therapies, pneumonitis occurred in 4% of patients treated with Zydelig compared to 1% on the comparator arms. Time to onset of pneumonitis ranged from <1 to 15 months. Monitor patients on Zydelig for pulmonary symptoms. In patients taking Zydelig who present with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic exam, or a decline by more than 5% in oxygen saturation, interrupt Zydelig until the etiology has been determined. If symptomatic pneumonitis or organizing pneumonia is diagnosed, initiate appropriate treatment with corticosteroids and permanently discontinue Zydelig.

5.4 Infections

(Additions and/or revisions are underlined)

Fatal and/or serious infections occurred in 21% of patients treated with Zydelig monotherapy and 48% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies. The most common infections were pneumonia, sepsis, and febrile neutropenia. Treat infections prior to initiation of Zydelig therapy. Monitor patients on Zydelig for signs and symptoms of infection, and interrupt Zydelig for Grade 3 or higher infection.

Serious or fatal Pneumocystis jirovecii pneumonia (PJP) or cytomegalovirus (CMV) occurred in <1% of patients treated with Zydelig. Provide PJP prophylaxis during treatment with Zydelig. Interrupt Zydelig in patients with suspected PJP infection of any grade, and permanently discontinue Zydelig if PJP infection of any grade is confirmed. Regular clinical and laboratory monitoring for CMV infection is recommended in patients with history of CMV infection or positive CMV serology at the start of treatment with Zydelig. Interrupt Zydelig in the setting of positive CMV PCR or antigen test until the viremia has resolved…

5.8 Neutropenia

(Additions and/or revisions are underlined)

Treatment-emergent Grade 3 or 4 neutropenia occurred in 25% of patients treated with Zydelig monotherapy and 58% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies...

5.9 Embryo-fetal Toxicity

(Additions and/or revisions are underlined)

Based on findings in animals and its mechanism of action, Zydelig may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of idelalisib to pregnant rats during organogenesis caused decreased fetal weight and congenital malformations at systemic exposures 12 times those reported in patients at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose.

6 Adverse Reactions

6.1 Clinical Trial Experience

(Additions and/or revisions are underlined)

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 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

Forty-two (38%) patients had dose interruptions and sixteen (15%) patients had dose reductions due to adverse reactions or laboratory abnormalities…

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 Greater than or Equal to 5% of Patients with CLL and Occurred at Greater than or Equal to 2% Higher Incidence in Patients Receiving Zydelig in Study 312-0116

Table 3 Hematologic and Hepatic Laboratory Abnormalities Reported in Greater than or Equal to 10% of Patients with CLL and Occurred at Greater than or Equal to 5% Higher Incidence in Patients Receiving Zydelig in Study 312-0116

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

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 146patients with indolent non-Hodgkin lymphoma (iNHL) treated with Zydelig 150 mg twice daily. 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

Adverse reactions resulted in interruption or discontinuation for 78 (53%) patients

Table 6 provides the adverse reactions occurring in at least 10% of patients receiving Zydelig monotherapy, and Table 7 provides the hematologic and hepatic laboratory abnormalities.

Table 6 Adverse Reactions Reported in Greater than or Equal to 10% of Patients with Indolent NHL Treated with Zydelig 150 mg BID

Table 7 Hematologic and Hepatic Laboratory Abnormalities in Patients with Indolent non-Hodgkin Lymphoma Treated with Zydelig 150 mg BID

 

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.

7 Drug Interactions

7.1 Effects of Other Drugs on Zydelig

(Additions and/or revisions are underlined)

Table 8 Drug Interactions with Zydelig that affect Idelalisib Concentrations (Table has been added; please refer to label)

7.2 Effects of Zydelig on Other Drugs

(Additions and/or revisions are underlined)

The coadministration of Zydelig with a CYP3A substrate may increase the concentrations of this CYP3A substrate. Avoid coadministration of Zydelig with sensitive CYP3A substrates.

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

Risk Summary

Based on findings in animal studies and the mechanism of action, 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.

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…

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

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 and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

Pregnancy

Based on animal studies, Zydelig may cause fetal harm when administered to a pregnant woman. 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. 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.

8.5 Geriatric Use

(Additions and/or revisions are underlined)

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

(Additions and/or revisions are underlined)

Dose adjustment is not recommended for patients with ALT or AST or bilirubin greater than or equal to upper limit of normal (ULN); however, limited safety and efficacy data are available for patients with baseline AST or ALT greater than or equal to 2.5 x ULN or bilirubin greater than or equal to 1.5 x ULN…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

  • Embryo-Fetal Toxicity - Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for 1 month after receiving the last dose of Zydelig. Advise lactating women not to breastfeed during treatment with Zydelig and for at least 1 month after the last dose.

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What is the most important information I should know about Zydelig?

Zydelig can cause serious side effects that can lead to death, including:

  • Lung problems (pneumonitis)… Your doctor may treat you with a corticosteroid medicine if you develop lung problems.

What is Zydelig?

Zydelig should not be used in combination with bendamustine and/or rituximab to treat people with FL.

Before taking Zydelig, tell your doctor about all of your medical conditions, including if you:

  • are pregnant or plan to become pregnant. Zydelig may harm your unborn baby. Females who are able to become pregnant should have a pregnancy test before starting treatment with Zydelig.

    • Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Zydelig and for 3 months after the last dose.

  • are breastfeeding or plan to breastfeed. It is not known if Zydelig passes into your breast milk. Do not breastfeed during your treatment with Zydelig and for at least 1 month after the last dose.

What are the possible side effects of Zydelig?

The most common side effects of Zydelig when used in combination with rituximab or with bendamustine and rituximab include:…

What are the ingredients in Zydelig?

Inactive ingredients: microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, sodium starch glycolate, and magnesium stearate. The tablet coating contains polyethylene glycol, talc, polyvinyl alcohol, titanium dioxide and FD&C Yellow #6 or Sunset Yellow FCF Aluminum Lake (for the 100 mg tablet) and red iron oxide (for the 150 mg tablet).

09/21/2016 (SUPPL-4)

Approved Drug Label (PDF)

Boxed Warning

WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, INFECTIONS, and INTESTINAL PERFORATION (additions and revisions are underlined)

See full prescribing information for complete boxed warning.

  • Fatal and/or serious hepatotoxicity occurred in 11% to 18% of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig.

  • Fatal and/or serious and severe diarrhea or colitis occurred in 14% to 19% of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig.

  • Fatal and/or serious pneumonitis occurred in 4% Zydelig-treated patients. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig.

  • Fatal and/or serious infections occurred in 21% to 36% of Zydelig-treated patients. Monitor for signs and symptoms of infection. Interrupt Zydelig if infection is suspected.

5 Warnings and Precautions

5.1 Hepatotoxicity

  • Fatal and/or serious hepatotoxicity occurred in 18% of patients treated with Zydelig monotherapy and 11% of patients treated with Zydelig in combination trials.

5.2 Severe Diarrhea or Colitis

  • Severe diarrhea or colitis (Grade 3 or higher) occurred in 14% of patients treated with Zydelig monotherapy and 19% of patients treated with Zydelig in combination trials  Zydelig and other drugs that cause diarrhea…Diarrhea due to Zydelig responds poorly to antimotility agents

5.3 Pneumonitis

  • Fatal and serious pneumonitis occurred in patients treated with Zydelig... In randomized clinical trials of combination therapies, pneumonitis occurred in 4% of patients treated with Zydelig compared to 1% on the comparator arms. Time to onset of pneumonitis ranged from <1 to 15 months.

5.4 Infections

  • Fatal and/or serious infections occurred in 21% of patients treated with Zydelig monotherapy and 36% of patients treated with Zydelig in combination trials. The most common infections were pneumonia, sepsis, and febrile neutropenia. Monitor patients for signs and symptoms of infection and interrupt Zydelig for Grade 3 or higher infection.

  • Serious or fatal Pneumocystis jirovecii pneumonia (PJP) or cytomegalovirus (CMV) occurred in less than1% of patients treated with Zydelig. Consider prophylaxis for PJP. Interrupt Zydelig in patients with suspected PJP infection of any grade, and permanently discontinue Zydelig if PJP infection of any grade is confirmed. Interrupt Zydelig in the setting of positive CMV PCR or antigen test until the infection has resolved. If Zydelig is subsequently resumed, patients should be monitored (by PCR or antigen test) for CMV reactivation at least monthly.

5.6 Severe Cutaneous Reactions

  • Fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have occurred in patients treated with Zydelig. If SJS or TEN is suspected, interrupt Zydelig until the etiology of the reaction has been determined. If SJS or TEN is confirmed, permanently discontinue Zydelig.

  • Other severe or life-threatening (Grade greater than or equal to 3) cutaneous reactions…

5.8 Neutropenia

  • Treatment-emergent Grade 3 or 4 neutropenia occurred in 25% of patients treated with Zydelig monotherapy and 46% of patients treated with Zydelig in combination trials. Monitor blood counts at least every 2 weeks for the first 6 months of therapy, and at least weekly in patients while neutrophil counts are less than 1.0 Gi/L.

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.

Addition of:

  • Infections

6.1 Clinical Trial Experience

Summary of Clinical Trials in Chronic Lymphocytic Leukemia

  • … 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%) subjects treated with Zydelig + rituximab. The most frequent serious adverse reactions reported for subjects treated with Zydelig 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%) subjects…

  • Forty-two subjects (38%) had dose interruptions… reasons for dose interruptions or reductions were pneumonia, diarrhea or colitis, rash, and elevated transamines.

  • Table 2: Adverse Reactions Reported in greater than or equal to 5% of Patients with CLL and which Occurred at greater than or equal to 2% Higher Incidence in Subjects Receiving Zydelig

    • Data in table has extensively changed; please refer to label.

  • Table 3: Treatment-emergent Laboratory Abnormalities Reported in greater than or equal to 10% of CLL Patients Occurring at a greater than or equal to 5% Higher Incidence in Subjects Receiving Zydelig

    • Data in table has extensively changed; please refer to label.

  • The following has been added following Table 3:

    • After closure of Study 1, 71 patients continued treatment with Zydelig on an extension study. The median duration of exposure was 18 months. Serious adverse reactions occurred in 48 (68%) subjects. 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%).

6.2 Postmarketing Experience (additional section)

  • 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)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

What is the most important information I should know about Zydelig?

Zydelig can cause serious side effects that can lead to death, including:

  • Liver problems. Abnormal liver blood test results are common during treatment with Zydelig. Zydelig can cause severe liver problems. Your doctor will do blood tests …

  • Infections. Zydelig can cause serious infections that may lead to death. Tell your doctor right away if you have a fever or any signs of an infection while taking Zydelig.

  • Severe diarrhea. Diarrhea is common during treatment with Zydelig …

  • Severe skin reactions. Tell your doctor right away if you get any of the following symptoms during treatment with Zydelig:

    • painful sores or ulcers on your skin, lips, or in your mouth

    • severe rash with blisters or peeling skin

    • rash with itching

What is Zydelig? (additions)

  • Chronic Lymphocytic Leukemia (CLL) in combination with rituximab when CLL comes back after prior cancer treatment and when rituximab treatment …

  • Zydelig should not be used as the first medicine to treat people who have been diagnosed with CLL, FL, or SLL.

  • Do not take Zydelig if you have a history of serious allergic reactions including a severe skin reaction called toxic epidermal necrolysis (TEN).

What should I tell my doctor before taking Zydelig?

  • Before taking Zydelig, tell your doctor about all of your medical conditions, including if you:

    • have an infection (addition)

    • are pregnant or plan to become pregnant. Zydelig may harm your unborn baby. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Zydelig and for at least 1 month after the last dose of Zydelig. Talk to your doctor about birth control methods that may be right for you. Tell your doctor right away if you become pregnant or think you are pregnant during treatment with Zydelig.

What are the possible side effects of Zydelig:

Low white blood cell count (neutropenia). Neutropenia is common during treatment with Zydelig and can sometimes be severe.

  • The most common side effects of Zydelig when used alone include:

    • tiredness

    • nausea

    • cough

    • fever

    • stomach area (abdomen) pain

    • pneumonia

    • rash

  • The most common side effects of Zydelig when used in combination with rituximab include:

    • pneumonia

    • fever

    • tiredness

    • rash

    • cough

    • nausea

Patient Counseling Information

  • Physicians and health care professionals are advised to discuss the following with patients prior to treatment with Zydelig:

    • Infections. Advise patients that Zydelig can cause serious infections that may be fatal. Advise patients to immediately report symptoms of infection (e.g. pyrexia).

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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