Scemblix Special Precautions

Myelosuppression: Thrombocytopenia, neutropenia, and anemia have occurred in patients receiving SCEMBLIX. Thrombocytopenia occurred in 98 of 356 (28%) patients receiving SCEMBLIX, with Grade 3 or 4 thrombocytopenia reported in 24 (7%) and 42 (12%) of patients, respectively. Among the patients with Grade 3 or 4 thrombocytopenia, median time to first occurrence of events was 6 weeks (range, 0.1 to 64 weeks). Of the 98 patients with thrombocytopenia, 7 (2%) patients permanently discontinued SCEMBLIX, while SCEMBLIX was temporarily withheld in 45 (13%) patients due to the adverse reaction.
Neutropenia occurred in 69 (19%) patients receiving SCEMBLIX, with Grade 3 and 4 neutropenia reported in 26 (7%) and 30 (8%) patients, respectively. Among the patients with Grade 3 or 4 neutropenia, median time to first occurrence of events was 6 weeks (range, 0.1 to 180 weeks). Of the 69 patients with neutropenia, 4 (1.1%) patients permanently discontinued SCEMBLIX, while SCEMBLIX was temporarily withheld in 34 (10%) patients due to the adverse reaction.
Anemia occurred in 46 (13%) patients receiving SCEMBLIX, with Grade 3 anemia occurring in 19 (5%) patients. Among the patients with Grade 3 or 4 anemia, median time to first occurrence of events was 30 weeks (range, 0.4 to 207 weeks). Of the 46 patients with anemia, SCEMBLIX was temporarily withheld in 2 (0.6%) patients due to the adverse reaction [see Clinical Trials Experience under Adverse Reactions].
Perform complete blood counts every two weeks for the first 3 months of treatment and monthly thereafter or as clinically indicated. Monitor patients for signs and symptoms of myelosuppression.
Based on the severity of thrombocytopenia and/or neutropenia, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX [see Dosage Modifications under Dosage & Administration].
Pancreatic Toxicity: Pancreatitis occurred in 9 of 356 (2.5%) patients receiving SCEMBLIX, with Grade 3 pancreatitis occurring in 4 (1.1%) patients. All cases of pancreatitis occurred in the Phase I study (X2101). Of the 9 patients with pancreatitis, two (0.6%) patients permanently discontinued SCEMBLIX, while SCEMBLIX was temporarily withheld in 4 (1.1%) patients due to the adverse reaction. Asymptomatic elevation of serum lipase and amylase occurred in 76 of 356 (21%) patients receiving SCEMBLIX, with Grade 3 and Grade 4 pancreatic enzyme elevations occurring in 36 (10%) and 8 (2.2%) patients, respectively. Of the 76 patients with pancreatic enzymes elevated, SCEMBLIX was permanently discontinued in 8 (2.2%) patients due to the adverse reaction [see Clinical Trials Experience under Adverse Reactions].
Assess serum lipase and amylase levels monthly during treatment with SCEMBLIX, or as clinically indicated. Monitor patients for signs and symptoms of pancreatic toxicity. Perform more frequent monitoring in patients with a history of pancreatitis. If lipase and amylase elevation are accompanied by abdominal symptoms, temporarily withhold SCEMBLIX and consider appropriate diagnostic tests to exclude pancreatitis [see Dosage Modifications under Dosage & Administration].
Based on the severity of lipase and amylase elevation, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX [see Dosage Modifications under Dosage & Administration].
Hypertension: Hypertension occurred in 68 of 356 (19%) patients receiving SCEMBLIX, with Grade 3 or 4 hypertension reported in 32 (9%) and 1 (0.3%) patients, respectively. Among the patients with Grade 3 or 4 hypertension, median time to first occurrence was 14 weeks (range, 0.1 to 156 weeks). Of the 68 patients with hypertension, SCEMBLIX was temporarily withheld in 3 (0.8%) patients due to the adverse reaction [see Clinical Trials Experience under Adverse Reactions].
Monitor and manage hypertension using standard antihypertensive therapy during treatment with SCEMBLIX as clinically indicated; for Grade 3 or higher hypertension, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of hypertension [see Dosage Modifications under Dosage & Administration].
Hypersensitivity: Hypersensitivity occurred in 115 of 356 (32%) patients receiving SCEMBLIX, with Grade 3 or 4 hypersensitivity reported in 6 (1.7%) patients [see Clinical Trials Experience under Adverse Reactions]. Reactions included rash, edema, and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity and initiate appropriate treatment as clinically indicated; for Grade 3 or higher hypersensitivity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of hypersensitivity [see Dosage Modifications under Dosage & Administration].
Cardiovascular Toxicity: Cardiovascular toxicity (including ischemic cardiac and CNS conditions, arterial thrombotic and embolic conditions) and cardiac failure occurred in 46 (13%) and in 9 (2.5%) of 356 patients receiving SCEMBLIX, respectively [see Clinical Trials Experience under Adverse Reactions]. Grade 3 cardiovascular toxicity was reported in 12 (3.4%) patients, while Grade 3 cardiac failure was observed in 5 (1.4%) patients. Grade 4 cardiovascular toxicity occurred in 2 (0.6%) patients, with fatalities occurring in 3 (0.8%) patients. Permanent discontinuation of SCEMBLIX occurred in 3 (0.8%) patients due to cardiovascular toxicity and in 1 (0.3%) patient due to cardiac failure, respectively. Cardiovascular toxicity occurred in patients with pre-existing cardiovascular conditions or risk factors, and/or prior exposure to multiple TKIs.
Arrhythmia, including QTc prolongation, occurred in 24 of 356 (7%) patients receiving SCEMBLIX, with Grade 3 arrhythmia reported in 8 (2%) patients. QTc prolongation occurred in 3 of 356 (0.8%) patients receiving SCEMBLIX, with Grade 3 QTc prolongation reported in 1 (0.3%) patient [see Clinical Trials Experience under Adverse Reactions].
Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated; for Grade 3 or higher cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of cardiovascular toxicity [see Dosage Modifications under Dosage & Administration].
Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, SCEMBLIX can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of asciminib to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes, including embryo-fetal mortality and malformations at maternal exposures (AUC) equivalent to or less than those in patients at the recommended doses. Advise pregnant women and females of reproductive potential of the potential risk to a fetus if SCEMBLIX is used during pregnancy or if the patient becomes pregnant while taking SCEMBLIX. Verify the pregnancy status of females of reproductive potential prior to starting treatment with SCEMBLIX. Females of reproductive potential should use effective contraception during treatment with SCEMBLIX and for 1 week after the last dose [see Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Renal Impairment: No dose adjustment is required for patients with mild to severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 89 mL/min/1.73 m²) and not requiring dialysis receiving SCEMBLIX [see Pharmacology: Pharmacokinetics under Actions].
Hepatic Impairment: No dose adjustment is required for patients with mild [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) >ULN or total bilirubin >1 to 1.5 times ULN and any AST] to severe hepatic impairment (total bilirubin >3 times ULN and any AST) receiving SCEMBLIX [see Pharmacology: Pharmacokinetics under Actions].
Use in Children: The safety and efficacy of SCEMBLIX in pediatric patients have not been established.
Use in the Elderly: In the ASCEMBL study, 44 of the 233 (19%) patients were 65 years of age or older and 6 (2.6%) were 75 years of age or older.
In the X2101 study, 16 of the 48 (33%) patients with the T315I mutation were 65 years of age or older and 4 (8%) were 75 years of age or older.
Overall, no differences in safety or efficacy of SCEMBLIX were observed between patients 65 years of age or older compared to younger patients. There is an insufficient number of patients 75 years of age or older to assess whether there are differences in safety or efficacy.