Ascimib Tablet

Ascimib Tablet is used for: Chronic Myeloid Leukemia

Oral Tablet Chronic Myeloid Leukemia Newly diagnosed Indicated in adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) 80 mg orally once daily or 40 mg orally twice daily. Continue for as long as clinical benefit is observed or until unacceptable toxicity Previously treated Indicated in adults with previously treated Ph+ CML in CP 80 mg orally once daily or 40 mg orally twice daily. Continue for as long as clinical benefit is observed or until unacceptable toxicity With T315I mutation Indicated in adults with Ph+ CML in CP with T315I mutation 200 mg orally twice daily. Continue for as long as clinical benefit is observed or until unacceptable toxicity

Renal impairment Mild-to-severe (eGFR 15-89 mL/min/1.73 m2, not requiring dialysis): No dosage adjustment necessary

Take without food Avoid eating for at least 2 hr before and 1 hr after taking a dose Once-daily dosing: Administer orally about the same time each day Swallow tablets whole; do NOT break, crush, or chew

Myelosuppression Severe thrombocytopenia, neutropenia, and anemia reported Median time to Grade 3 or 4 thrombocytopenia, neutropenia, and anemia: 6 weeks, 7 weeks, and 22 weeks, respectively Perform complete blood counts every 2 weeks for first 3 months and monthly thereafter or as clinically indicated Monitor for signs and symptoms of myelosuppression Hold, reduce dose, or permanently discontinue based on severity Pancreatic toxicity Pancreatitis reported Assess serum lipase and amylase monthly during therapy or as clinically indicated Monitor for signs and symptoms of pancreatic toxicity Hold, reduce dose, or permanently discontinue based on severity of lipase or amylase elevation Increase monitoring frequency in patients with history of pancreatitis Hold and consider appropriate diagnostic tests to exclude pancreatitis if lipase or amylase elevation accompanied by abdominal symptoms Hypertension Severe hypertension can occur Median time to Grade 3 or 4 hypertension: 32 weeks Monitor and manage using standard antihypertensive therapy as clinically indicated Hold, reduce dose, or permanently discontinue for Grade 3 or higher hypertension depending on persistence Hypersensitivity Hypersensitivity reactions (eg, rash, edema, and bronchospasm) can occur Monitor for signs and symptoms of hypersensitivity; initiate appropriate treatment as clinically indicated Hold, reduce dose, or permanently discontinue for Grade 3 or higher hypersensitivity reactions depending on persistence Cardiovascular toxicity Cardiovascular toxicity (eg, ischemic cardiac and CNS conditions, arterial thrombotic and embolic conditions) and heart failure reported, including fatal cases Arrhythmia, including QTc prolongation may also occur Most cases of cardiovascular toxicity occurred in patients with preexisting cardiovascular conditions or risk factors and/or prior exposure to multiple tyrosine kinase inhibitors Monitor patients with history of cardiovascular risk factors for signs and symptoms of cardiovascular toxicity; initiate appropriate treatment as clinically indicated Hold, reduce dose, or permanently discontinue for Grade 3 or higher cardiovascular toxicity depending on persistence Embryo-fetal toxicity May cause fetal harm when administered during pregnancy Advise pregnant patients and females of reproductive potential of potential fetal risks Verify the pregnancy status of females of reproductive potential prior to initiating therapy Females of reproductive potential should use effective contraception

Pregnancy Based on animal studies and the mechanism of action, embryofetal harm may occur when administered to pregnant females There are no available data on use in pregnant females to evaluate any drug-associated risks Verify the pregnancy status of females of reproductive potential before initiating therapy Contraception Females of reproductive potential: Use effective contraception during treatment and for 1 week after last dose Infertility Based on animal studies, fertility may be impaired in females of reproductive potential; reversibility on the effect on fertility is unknown Animal data Pregnant rats Maternal toxicity occurred at 600 mg/kg/day, resulting in early termination of the dose group Adverse embryofetal findings were observed at 25 and 150 mg/kg; no maternal toxicities occurred Increases in fetal weights at 25 and 150 mg/kg/day were observed Malformations were evident at 150 mg/kg and included cleft palate, anasarca (edema), and cardiac abnormalities Pregnant rabbits Maternal toxicity occurred at 300 mg/kg/day, resulting in early termination of the dose group Adverse embryofetal findings were observed at 50 mg/kg; no maternal toxicities occurred; findings include increases in early resorptions and postimplantation loss, decreases in number of live fetuses, and cardiac malformations Lactation There are no data on presence of asciminib or its metabolites in human milk, effects on breastfed infants, or effects on milk production Advise females not to breastfeed during treatment and for 1 week after last dose

CYP3A4 substrate Inhibitor of CYP3A4, CYP2C9, and P-glycoprotein (P-gp) Strong CYP3A4 inhibitors Closely monitor for adverse reactions, especially in patients treated at 200 mg q12hr Strong CYP3A4 inhibitor increases both plasma concentrations and risk of toxicities of asciminib Itraconazole oral solution containing hydroxypropyl-beta-cyclodextrin Avoid coadministration Itraconazole oral solution containing hydroxypropyl-beta-cyclodextrin decreases asciminib plasma concentration and efficacy Sensitive CYP3A4 substrates 80 mg/day dosing: Closely monitor for adverse reactions 200 mg q12hr dosing: Avoid coadministration Asciminib increases plasma levels of sensitive CYP3A4 substrates and risk of adverse reactions of these substrates Sensitive CYP2C9 substrates Avoid coadministration 80 mg/day-dosing: If coadministration unavoidable, consider reducing CYP2C9 substrate dosage as recommended in its prescribing information 200 mg q12hr-dosing: If coadministration unavoidable, consider alternative therapy with non-CYP2C9 substrate Asciminib increases plasma levels and risk of adverse reactions of sensitive CYP2C9 substrates Sensitive P-gp substrates Closely monitor for adverse reactions of P-gp substrates Asciminib increases the plasma concentrations and risk of adverse reactions of P-gp substrates Contraindicated (1) deuruxolitinib Serious (3) atrasentan etrasimod resmetirom

Side effects of Asciminib : >50% All grades Lymphocyte count decreased (20-71%) Leukocyte count decreased (54%) >10-50% All grades Potassium increased (48%) ALT increased (26-48%) Platelet count decreased (25-48%) Neutrophil count decreased (43-46%) Triglycerides increased (20-46%) Lipase increased (15-46%) Hemoglobin decreased (24-44%) Musculoskeletal pain (24-42%) Calcium corrected decreased (16-42%) Uric acid increased (21-40%) Phosphate decreased (18-40%) AST increased (21-35%) Cholesterol increased (12-34%) Fatigue (18-31%) Creatinine increased (15-31%) Creatine kinase increased (30%) Hypersensitivity (30%) Amylase increased (13-29%) Thrombocytopenia (28%) Rash (18-27%) Infection (26%) Alkaline phosphatase increased (13-25%) Bilirubin increased (12-23%) Neutropenia (22%) Headache (14-21%) Diarrhea (13-21%) Vomiting (<19%) Abdominal pain (14-17%) Arthralgia (<17%) Hypertension (16%) Upper respiratory tract infection (13-15%) Hemorrhage (<15%) Cough (<15%) Dyslipidemia (≤14%) Anemia (13%) Pruritus (<13%) Potassium decreased (11%) Cardiovascular toxicity (11%) Grade 3 or 4 Nausea (<27%) Platelet count decreased (12-24%) Neutrophil count decreased (12-22%) Lipase increased (4.5-21%) Thrombocytopenia (17%) Neutropenia (13%) 1-10% All grades Edema (<10%) Constipation (<10%) Decreased appetite (<10%) Dizziness (<10%) Dry eye (<10%) Dyspnea (<10%) Febrile neutropenia (<10%) Hypothyroidism (<10%) Influenza (<10%) Lower respiratory tract infection (<10%) Palpitations (<10%) Peripheral neuropathy (<10%) Pleural effusion (<10%) Pneumonia (<10%) Pyrexia (<10%) Urinary tract infection (<10%) Urticaria (<10%) Vision blurred (<10%) Arrhythmia including QTc prolongation (6%) Heart failure (2.3%) Pancreatitis (2%) Grade 3 or 4 Amylase increased (1.3-10%) Hypertension (9.2%) Abdominal pain (<8%) Phosphate decreased (6%) Vomiting (6%) Uric acid increased (4.2-6%) ALT increased (<6%) Leukocyte count decreased (5%) Triglycerides increased (1-5%) Edema (4.2%) Lymphocyte count decreased (3-4.2%) Hemoglobin decreased (2-4.2%) Musculoskeletal pain (1.5-4.2%) Anemia (4%) Cardiovascular toxicity (3.2%) Creatine kinase increased (2.6%) Arrhythmia including QTc prolongation (2.2%) Diarrhea (2.1%) Hemorrhage (2.1%) Potassium increased (2.1%) AST increased (1.9-2.1%) Headache (<2.1%) Fatigue (<2.1%) Hypersensitivity (1.3%) Heart failure (1.1%) Pancreatitis (1.1%) Dyslipidemia (1%)

ABL/BCR-ABL1 tyrosine kinase inhibitor Binds to ABL myristoyl pockets, which inhibits the ABL1 kinase activity of the BCR-ABL1 fusion protein

Ascimib 40 mg Tablet manufactured by Everest Pharmaceuticals Ltd.. Its generic name is Asciminib. Ascimib is availble in Bangladesh. Farmaco BD drug index information on Ascimib Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.