SCEMBLIX

/ Novartis

Ph+ CML-CP, Previously Treated with Two or More TKIs
The recommended dose is 80 mg taken orally once daily at approximately the same time each day or 40 mg orally twice daily at approximately 12-hour intervals. The recommended dose is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after.
Ph+ CML-CP with the T315I Mutation
The recommended dose is 200 mg taken orally twice daily at approximately 12-hour intervals. The recommended dose is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after.
Missed Dose
Once Daily Dosage Regimen: If dose is missed by more than approximately 12 hours, skip the dose and take the next dose as scheduled.
Twice Daily Dosage Regimens: If dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled.
See prescribing information for full details.

* Treatment of adult patients with: Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs).
* Ph+ CML in CP with the T315I mutation

Hypersensitivity to the active substance or to any of the excipients

Myelosuppression
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.
Thrombocytopenia, neutropenia, and anemia have occurred in patients receiving asciminib. Thrombocytopenia occurred in 98 of 356 (28%) patients, 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).
Neutropenia occurred in 69 (19%) patients, 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).
Anemia occurred in 46 (13%) patients, 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).
Pancreatic Toxicity
Pancreatitis occurred in 9 of 356 (2.5%) patients receiving asciminib, with Grade 3 pancreatitis occurring in 4 (1.1%) patients. Asymptomatic elevation of serum lipase and amylase occurred in 76 of 356 (21%) patients, with Grade 3 and Grade 4 pancreatic enzyme elevations occurring in 36 (10%) and 8 (2.2%) patients, respectively.
Assess serum lipase and amylase levels monthly during treatment, 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 asciminib and consider appropriate diagnostic tests to exclude pancreatitis.
Based on the severity of lipase and amylase elevation, reduce dose, temporarily withhold, or permanently discontinue.
Hypertension
Hypertension occurred in 68 of 356 (19%) patients receiving asciminib, 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).
Monitor and manage hypertension using standard antihypertensive therapy during treatment as clinically indicated; for Grade 3 or higher hypertension, temporarily withhold, reduce dose, or permanently discontinue depending on persistence of hypertension.
Hypersensitivity
Hypersensitivity occurred in 115 of 356 (32%) patients receiving asciminib, with Grade 3 or 4 hypersensitivity reported in 6 (1.7%) patients. 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 depending on persistence of hypersensitivity.
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 asciminib, respectively. 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. 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 asciminib, with Grade 3 arrhythmia reported in 8 (2%) patients. QTc prolongation occurred in 3 of 356 (0.8%) patients receiving asciminib, with Grade 3 QTc prolongation reported in 1 (0.3%) patient.
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 depending on persistence of cardiovascular toxicity.
Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, asciminib can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to starting treatment. Females of reproductive potential should use effective contraception during treatment and for 1 week after the last dose.

Adverse Reactions in Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs
The most common (≥ 20%) adverse reactions in patients who received asciminib 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 asciminib 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.
Adverse Reactions in Patients with Ph+ CML-CP with the T315I Mutation
The most common (≥ 20%) adverse reactions in patients who received asciminib were musculoskeletal pain, fatigue, nausea, rash, and diarrhea.
The most common select laboratory abnormalities that worsened from baseline in ≥ 20% of patients who received asciminib 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.
See prescribing information for full details.

Effect of Other Drugs on Asciminib
Strong CYP3A4 Inhibitors
Asciminib is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases both the asciminib Cmax and AUC, which may increase the risk of adverse reactions. Closely monitor for adverse reactions in patients treated with asciminib at 200 mg twice daily with concomitant use of strong CYP3A4 inhibitors.
Itraconazole Oral Solution Containing Hydroxypropyl-β-cyclodextrin
Concomitant use of asciminib with itraconazole oral solution containing hydroxypropyl-β-cyclodextrin decreases asciminib Cmax and AUC, which may reduce this medical product efficacy. Avoid coadministration of asciminib at all recommended doses with itraconazole oral solution containing hydroxypropyl-β-cyclodextrin.
Strong CYP3A4 Inducers
Concomitant use of asciminib with strong CYP3A4 inducers decreases both the asciminib Cmax and AUC.
Effect of Asciminib on Other Drugs
Certain CYP3A4 Substrates
Asciminib is a CYP3A4 inhibitor. Concomitant use of asciminib increases the Cmax and AUC of CYP3A4 substrates, which may increase the risk of adverse reactions of these substrates.
Closely monitor for adverse reactions in patients treated with asciminib at 80 mg total daily dose with concomitant use of certain CYP3A4 substrates, where minimal concentration changes may lead to serious adverse reactions. Avoid coadministration of asciminib at 200 mg twice daily with certain CYP3A4 substrates, where minimal concentration changes may lead to serious adverse reactions.
CYP2C9 Substrates
Asciminib is a CYP2C9 inhibitor. Concomitant use of asciminib increases the Cmax and AUC of CYP2C9 substrates, which may increase the risk of adverse reactions of these substrates.
Avoid coadministration of asciminib at 80 mg total daily dose with certain CYP2C9 substrates, where minimal concentration changes may lead to serious adverse reactions. If coadministration is unavoidable, reduce the CYP2C9 substrate dosage as recommended in its prescribing information.
Avoid coadministration of asciminib at 200 mg twice daily with sensitive CYP2C9 substrates and certain CYP2C9 substrates, where minimal concentration changes may lead to serious adverse reactions. If coadministration is unavoidable, consider alternative therapy with a non-CYP2C9 substrate.
Certain P-gp Substrates
Asciminib is a P-gp inhibitor. Concomitant use of asciminib increases the plasma concentrations of P-gp substrates, which may increase the risk of adverse reactions of these substrates.
Closely monitor for adverse reactions in patients treated with asciminib at all recommended doses with concomitant use of P-gp substrates, where minimal concentration changes may lead to serious toxicities.
Substrates of BCRP
Asciminib is a BCRP inhibitor. Concomitant use of asciminib may increase the plasma concentration of BCRP substrates, which may increase the risk of adverse reactions associated with these substrates.
Avoid coadministration of asciminib at all recommended doses with rosuvastatin . Closely monitor for adverse reactions in patients treated with asciminib at all recommended doses with concomitant use of other BCRP substrates. Reduce the dosage of the other BCRP substrates as recommended in their Prescribing Information when used concomitantly with asciminib at all recommended doses.

Pregnancy: Based on findings from animal studies and the mechanism of action, asciminib can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on this medical product use in pregnant women to evaluate a drug associated risk. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment and for 1 week after the last dose.
Lactation: There are no data on the presence of asciminib or its metabolites in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 1 week after the last dose.