openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Diarrhea: VERZENIO can cause severe cases of diarrhea, associated with dehydration and infection. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. ( 2.2 , 5.1 ) Neutropenia: Monitor complete blood counts prior to the start of VERZENIO therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. ( 2.2 , 5.2 ) Interstitial Lung Disease (ILD)/Pneumonitis: Severe and fatal cases of ILD/pneumonitis have been reported. Monitor for clinical symptoms or radiological changes indicative of ILD/pneumonitis. Permanently discontinue VERZENIO in all patients with Grade 3 or 4 ILD or pneumonitis. ( 2.2 , 5.3 ) Hepatotoxicity: Increases in serum transaminase levels have been observed. Perform liver function tests (LFTs) before initiating treatment with VERZENIO. Monitor LFTs every two weeks for the first two months, monthly for the next 2 months, and as clinically indicated. ( 2.2 , 5.4 ) Venous Thromboembolism: Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. ( 2.2 , 5.5 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Diarrhea Severe diarrhea associated with dehydration and infection occurred in patients treated with VERZENIO. Across four clinical trials in 3691 patients, diarrhea occurred in 81% to 90% of patients who received VERZENIO. Grade 3 diarrhea occurred in 8% to 20% of patients receiving VERZENIO [see Adverse Reactions ( 6.1 )]. Most patients experienced diarrhea during the first month of VERZENIO treatment. The median time to onset of the first diarrhea event ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19% to 26% of patients with diarrhea required a VERZENIO dose interruption and 13% to 23% required a dose reduction. Instruct patients to start antidiarrheal therapy such as loperamide at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow up [see Patient Counseling Information ( 17 )]. For Grade 3 or 4 diarrhea, or diarrhea that require...
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea [see Warnings and Precautions ( 5.1 )] . Neutropenia [see Warnings and Precautions ( 5.2 )] . Interstitial Lung Disease (ILD) or Pneumonitis [see Warnings and Precautions ( 5.3 )] . Hepatotoxicity [see Warnings and Precautions ( 5.4 )] . Venous Thromboembolism [see Warnings and Precautions ( 5.5 )] . Most common adverse reactions (incidence ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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. The safety population described in the Warnings and Precautions reflect exposure to VERZENIO in 3691 patients from four clinical trials: monarchE, MONARCH 1, MONARCH 2, and MONARCH 3. The safety population includes exposure to VERZENIO as a single agent at 200 mg twice daily in 132 patients in MONARCH 1 and to VERZENIO at 150 mg twice daily in 3559 patients administered in combination with fulvestrant, tamoxifen, or an aromatase inhibitor in monarchE, MONARCH 2, and MONARCH 3. The median duration of exposure ranged from 4.5 months in MONARCH 1 to 24 months in monarchE. The most common adverse reactions (incidence ≥20%) across clinical trials were: diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia. Early Breast Cancer monarchE: VERZENIO in Combination with Tamoxifen or an Aromatase Inhibitor as Adjuvant Treatment Adult patients with HR-positive, HER2-negative, node-positive early breast cancer at a high risk of recurrence The safety of VERZENIO was evaluated in monarchE, a study of 5591 adult patients receiving VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor) or endocrine therapy (tamoxifen or an aromatase inhibitor) alone [see Clinical Studies ( 14.1 )...
adverse reactions table
Table 8: Adverse Reactions (≥10%) of Patients Receiving VERZENIO Plus Tamoxifen or an Aromatase Inhibitor [with a Difference between Arms of ≥2%] in monarchE a Includes the following fatal adverse reactions: diarrhea (n=1), and infections (n=4) b Includes the following fatal adverse reactions: infections (n=5) c Includes mouth ulceration, mucosal inflammation, oropharyngeal pain, stomatitis. d Includes all reported preferred terms that are part of the Infections and Infestations system organ class. Most common infections (>5%) include upper respiratory tract infection, urinary tract infection, and nasopharyngitis. e Includes asthenia, fatigue. f Includes exfoliative rash, mucocutaneous rash, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash maculovesicular, rash morbilliform, rash papular, rash papulosquamous, rash pruritic, rash vesicular, vulvovaginal rash. VERZENIO Plus Tamoxifen or an Aromatase Inhibitor N=2791Tamoxifen or an Aromatase Inhibitor N=2800All Gradesa %Grade 3 %Grade 4 %All Gradesb %Grade 3 %Grade 4 %Gastrointestinal Disorders Diarrhea 84 8 0 9 0.2 0 Nausea 30 0.5 0 9 <0.1 0 Vomiting 18 0.5 0 4.6 0.1 0 Stomatitisc14 0.1 0 5 0 0 Infections and Infestations Infectionsd51 4.9 0.6 39 2.7 0.1 General Disorders and Administration Site Conditions Fatiguee41 2.9 0 18 0.1 0 Nervous System Disorders Headache 20 0.3 0 15 0.2 0 Dizziness 11 0.1 0 7 <0.1 0 Metabolism and Nutrition Disorders Decreased appetite 12 0.6 0 2.4 <0.1 0 Skin and Subcutaneous Tissue Disorders Rashf11 0.4 0 4.5 0 0 Alopecia 11 0 0 2.7 0 0