Scemblix Adverse Reactions

The following clinically significant adverse reactions can occur with SCEMBLIX and are discussed in greater detail in Precautions: Myelosuppression, Pancreatic Toxicity, Hypertension, Hypersensitivity, Cardiovascular Toxicity.
Clinical Trials 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 pooled safety population described in the Precautions reflects exposure to SCEMBLIX at 10 mg to 200 mg orally twice daily (between 0.25 to 5 times the recommended dosage for the 80 mg daily dosage and between 0.05 times and up to the recommended dosage for the 200 mg twice daily dosage) in 356 patients enrolled in one of two clinical trials, including patients with Ph+ CML in CP receiving SCEMBLIX as monotherapy: study CABL001A2301 (ASCEMBL) and study CABL001X2101 [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Among the 356 patients receiving SCEMBLIX, the median duration of exposure to SCEMBLIX was 116 weeks (range, 0.1 to 342 weeks).
Adverse Reactions in Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs: The clinical trial randomized and treated 232 patients with Ph+ CML-CP, previously treated with two or more TKIs to receive SCEMBLIX 40 mg twice daily or bosutinib 500 mg once daily (ASCEMBL) [see Pharmacology: Pharmacodynamics: Clinical Studies: Ph+ CML-CP, Previously Treated with Two or More TKIs under Actions]. The safety population (received at least 1 dose of SCEMBLIX) included 156 patients with Ph+ CML-CP, previously treated with two or more TKIs. Among patients who received SCEMBLIX, 83% were exposed for 24 weeks or longer and 56% were exposed for 96 weeks or longer.
Serious adverse reactions occurred in 18% of patients who received SCEMBLIX. Serious adverse reactions in ≥1% included cardiac failure congestive (1.9%), pyrexia (1.9%), urinary tract infection (1.9%), headache (1.3%), and thrombocytopenia (1.3%). Two patients (1.3%) had a fatal adverse reaction, one each for mesenteric artery thrombosis and ischemic stroke.
Permanent discontinuation of SCEMBLIX due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of SCEMBLIX in >2% of patients included thrombocytopenia (3.2%) and neutropenia (2.6%).
Dosage interruptions of SCEMBLIX due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption in >5% of patients included thrombocytopenia (19%) and neutropenia (18%).
Dose reductions of SCEMBLIX due to an adverse reaction occurred in 6% of patients. Adverse reactions which required dose reductions in >1% of patients included thrombocytopenia (4.5%) and neutropenia (1.3%).
The most common (≥20%) adverse reactions in patients who received SCEMBLIX were upper respiratory tract infections, musculoskeletal pain, headache, and fatigue.
The most common select laboratory abnormalities that worsened from baseline in ≥20% of patients who received SCEMBLIX were platelet count decreased, triglycerides increased, neutrophil count decreased, hemoglobin decreased, creatine kinase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, uric acid increased, and lymphocyte count decreased.
Table 5 summarizes the adverse reactions in ASCEMBL. (See Table 5.)

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Clinically relevant adverse reactions in <10% of patients treated with SCEMBLIX in ASCEMBL included: cough, dyspnea, pleural effusion, dizziness, neuropathy peripheral, edema, pyrexia, vomiting, constipation, dyslipidemia, decreased appetite, pruritus, urticaria, lower respiratory tract infection, influenza, urinary tract infection, pneumonia, hemorrhage, arrhythmia (including electrocardiogram QT prolonged), palpitations, cardiac failure congestive, vision blurred, dry eye, hypothyroidism, and febrile neutropenia.
Table 6 summarizes the laboratory abnormalities in ASCEMBL. (See Table 6.)

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Adverse Reactions in Patients with Ph+ CML-CP with the T315I Mutation: The single-arm clinical trial enrolled patients with Ph+ CML-CP with the T315I mutation [see Pharmacology: Pharmacodynamics: Clinical Studies: Ph+ CML-CP with the T315I Mutation under Actions]. The safety population (received at least 1 dose of SCEMBLIX) included 48 patients with Ph+ CML-CP with the T315I mutation who received 200 mg of SCEMBLIX twice daily. Among these patients, 83% were exposed for 24 weeks or longer, and 75% were exposed for 48 weeks or longer.
Serious adverse reactions occurred in 23% of patients who received SCEMBLIX. Serious adverse reactions in >1% included abdominal pain (4.2%), vomiting (4.2%), pneumonia (4.2%), musculoskeletal pain (2.1%), headache (2.1%), hemorrhage (2.1%), constipation (2.1%), arrhythmia (2.1%), and pleural effusion (2.1%).
Permanent discontinuation of SCEMBLIX due to an adverse reaction occurred in 10% of patients. Adverse reactions which resulted in permanent discontinuation of SCEMBLIX in >2% of patients included pancreatic enzymes increased (2.1%).
Dosage interruptions of SCEMBLIX due to an adverse reaction occurred in 31% of patients. Adverse reactions which required dosage interruption in >5% of patients included pancreatic enzymes increased (17%) and thrombocytopenia (8%).
Dose reductions of SCEMBLIX due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reductions in >1% of patients included pancreatic enzymes increased (10%), abdominal pain (4.2%), anemia (2.1%), blood bilirubin increased (2.1%), dizziness (2.1%), fatigue (2.1%), hepatic enzymes increased (2.1%), musculoskeletal pain (2.1%), nausea (2.1%), neutropenia (2.1%), pruritus (2.1%), and thrombocytopenia (2.1%).
The most common (≥20%) adverse reactions in patients who received SCEMBLIX were musculoskeletal pain, fatigue, nausea, rash, and diarrhea.
The most common select laboratory abnormalities that worsened from baseline in ≥20% of patients who received SCEMBLIX were alanine aminotransferase (ALT) increased, lipase increased, triglycerides increased, hemoglobin decreased, neutrophil count decreased, lymphocyte count decreased, phosphate decreased, aspartate aminotransferase (AST) increased, amylase increased, platelet count decreased, and bilirubin increased.
Table 7 summarizes adverse reactions in study X2101. (See Table 7.)

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Clinically relevant adverse reactions in <10% of patients treated with SCEMBLIX in X2101 included: constipation, pancreatitis, pyrexia, dizziness, neuropathy peripheral, pneumonia, lower respiratory tract infection, dyspnea, pleural effusion, dry eye, vision blurred, arrhythmia, palpitations, cardiac failure congestive, decreased appetite, dyslipidemia, hypersensitivity, and urticaria.
Table 8 summarizes laboratory abnormalities in X2101. (See Table 8.)

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