Asciminib is a BCR-ABL1 inhibitor specifically targeting the ABL myristoyl pocket (STAMP). It is indicated for the treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adult patients who had previously received 2 or more tyrosine kinase inhibitors and in adult patients with chronic phase Ph+ CML with the T315I mutation. Myelosuppression, pancreatitis, and hypertension have been reported with asciminib therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Take asciminib on an empty stomach; avoid eating for at least 2 hours before and 1 hour after taking it.
-Swallow tablets whole; do not break, crush, or chew tablets.
-Skip the missed dose and take the next dose at the regular time if a dose is missed by more than 12 hours for once-daily dosing or more than 6 hours with twice-daily dosing.
Hematologic toxicity was reported with asciminib therapy. Monitor patients for signs and symptoms of myelosuppression and obtain complete blood counts every 2 weeks for the first 3 months of treatment and then monthly thereafter or as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe hematologic toxicity. Anemia (13%; grade 3, 5%), neutropenia (19%; grade 3, 7%; grade 4, 8%), and thrombocytopenia (28%; grade 3, 7%; grade 4, 12%) were reported in patients with chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib (dose range, 10 mg to 200 mg twice daily) in a pooled safety population (n = 356) from clinical trials. In patients with grade 3 or 4 anemia, neutropenia, and thrombocytopenia, the median times to first event occurrence were 30 (range, 0.4 to 207) weeks, 6 (range, 0.1 to 180) weeks, and 6 (range, 0.1 to 64) weeks, respectively. Decreased platelet count (46% and 25%; grade 3 or 4, 24% and 15%), neutrophil count (43% and 44%; grade 3 or 4, 22% and 15%), hemoglobin concentration (37% and 44%; grade 3 or 4, 2% and 4.2%), and lymphocyte count/lymphopenia (20% and 42%; grade 3 or 4, 3.3% and 4.2%) that worsened from baseline occurred in patients with previously treated chronic phase Ph+ CML who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Febrile neutropenia occurred in less than 10% of patients with previously treated chronic phase Ph+ CML.
Pancreatic toxicity was reported with asciminib therapy. Monitor patients for signs and symptoms of pancreatic toxicity; increase the frequency of monitoring in patients with a history of pancreatitis. Obtain serum amylase and lipase levels monthly or as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop elevated pancreatic enzymes. Asymptomatic elevation of amylase and lipase levels (21%; grade 3, 10%; grade 4, 2.2%) and pancreatitis (2.5%; grade 3, 1.1%) were reported in patients with chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib (dose range, 10 mg to 200 mg twice daily) in a pooled safety population (n = 356) from clinical trials. All 9 patients who developed pancreatitis had chronic phase Ph+ CML with the T315I mutation and received asciminib 200 mg twice daily. Increased lipase level occurred in 15% (grade 3 or 4, 4.5%) and 46% (grade 3 or 4, 21%) of patients with previously treated chronic phase Ph+ CML who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Hyperamylasemia was reported in less than 13% (grade 3 or 4, 1.3%) and 29% (grade 3 or 4, 10%) of patients, respectively.
Increased blood pressure was reported with asciminib therapy. Monitor patients for signs of high blood pressure; manage patients per standard clinical guidelines. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe hypertension. Hypertension was reported in 19% (grade 3, 9%; grade 4, 0.3%) of patients with chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib (dose range, 10 mg to 200 mg twice daily) in a pooled safety population (n = 356) from clinical trials. The median time to first onset of hypertension was 14 (range, 0.1 to 156) weeks. Hypertension including hypertensive crisis occurred in 14% (grade 3 or 4, 7%) and 13% (grade 3 or 4, 8%) of patients with previously treated chronic phase Ph+ CML who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials.
Cardiovascular toxicity (i.e., ischemic cardiac and central nervous system conditions, arterial thrombotic and embolic conditions/thromboembolism) (13%; grade 3, 3.4%; grade 4, 0.6%; grade 5, 0.8%), cardiac arrhythmias (7%; grade 3, 2%) including QT prolongation (0.8%; grade 3, 0.3%), and heart failure (2.5%; grade 3, 1.4%) were reported in patients with chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib (dose range, 10 mg to 200 mg twice daily) in a pooled safety population (n = 356) from clinical trials. Fatal mesenteric artery thrombosis and ischemic stroke were each reported in 1 patient with previously treated chronic phase Ph+ CML. Additionally, palpitations occurred in less than 10% of patients. Monitor patients with a history of cardiac disease or cardiac risk factors for signs or symptoms of cardiotoxicity; initiate appropriate treatment as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe cardiovascular toxicity.
Upper respiratory tract infection occurred in 26% (grade 3 or 4, 0.6%) and 13% of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Urinary tract infection and influenza were each reported in less than 10% of patients with previously treated chronic phase Ph+ CML. Additionally, lower respiratory tract infection and pneumonia each occurred in less than 10% of patients with chronic phase Ph+ CML. The term upper respiratory tract infection included nasopharyngitis, rhinitis, pharyngitis, and pharyngotonsillitis.
Musculoskeletal pain occurred in 24% (grade 3 or 4, 2.6%) and 42% (grade 3 or 4, 4.2%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Arthralgia was reported in 13% (grade 3 or 4, 0.6%) and 17% of these patients, respectively. Additionally, increased creatine kinase level that worsened from baseline was reported in 30% (grade 3 or 4, 2.6%) of patients with previously treated chronic phase Ph+ CML. The term musculoskeletal pain included pain in extremity, back pain, myalgia, non-cardiac/musculoskeletal chest pain, bone pain, and arthritis.
Headache including migraine occurred in 21% (grade 3 or 4, 1.9%) and 19% (grade 3 or 4, 2.1%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Additionally, dizziness and peripheral neuropathy each occurred in less than 10% of patients with chronic phase Ph+ CML.
Fatigue including asthenia occurred in 20% (grade 3 or 4, 0.6%) and 31% (grade 3 or 4, 2.1%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials.
Rash occurred in 18% (grade 3 or 4, 0.6%) and 27% of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Pruritus was reported in less than 10% and 13% of patients, respectively. Additionally, urticaria occurred in less than 10% of patients with chronic phase Ph+ CML. The term rash included maculopapular rash, acneiform rash/dermatitis, eczema, skin exfoliation, morbilliform rash, and erythema multiforme.
Gastrointestinal toxicity including diarrhea including colitis (12% and 21%; grade 3 or 4, 0% and 2.1%), nausea (12% and 27%; grade 3 or 4, 0.6% and 0%), and abdominal pain (10% and 17%; grade 3 or 4, 0% and 8%) occurred in patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Vomiting was reported in less than 10% and 19% (grade 3 or 4, 6%) of patients, respectively. Additionally, constipation and decreased appetite/anorexia each occurred in less than 10% of patients with chronic phase Ph+ CML. The term abdominal pain included abdominal tenderness, epigastric discomfort, and hepatic pain.
Edema occurred in less than 10% and 10% (grade 3 or 4, 4.2%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials.
Cough occurred in less than 10% and 15% of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Additionally, dyspnea and pleural effusion each occurred in less than 10% of patients with chronic phase Ph+ CML.
Bleeding occurred in less than 10% and 15% (grade 3 or 4, 2.1%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. The term bleeding included epistaxis, ear hemorrhage, mouth hemorrhage, post procedural hemorrhage, skin hemorrhage, and vaginal bleeding.
Fever occurred in less than 10% of patients with Philadelphia chromosome-positive chronic myeloid leukemia who received asciminib in clinical trials.
Xerophthalmia/dry eye and blurred vision each occurred in less than 10% of patients with Philadelphia chromosome-positive chronic myeloid leukemia who received asciminib in clinical trials.
Hypertriglyceridemia that worsened from baseline occurred in 44% (grade 3 or 4, 5%) and 46% (grade 3 or 4, 2.1%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Hypercholesterolemia that worsened from baseline was reported in 12% and 15% of patients, respectively. Additionally, hyperlipidemia/dyslipidemia occurred in less than 10% of patients with chronic phase Ph+ CML who received asciminib in clinical trials.
Hypothyroidism occurred in less than 10% of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia who received asciminib 40 mg twice daily (n = 156) in a randomized trial.
Hypersensitivity reactions were reported with asciminib therapy. Monitor for signs and symptoms of hypersensitivity; initiate appropriate treatment as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop a severe hypersensitivity reaction. Hypersensitivity including rash, edema, and bronchospasm occurred in 32% (grade 3 or 4, 1.7%) of patients with chronic phase Philadelphia chromosome-positive chronic myeloid leukemia who received asciminib (dose range, 10 mg to 200 mg twice daily) in a pooled safety population (n = 356) from 2 clinical trials.
Hyperuricemia that worsened from baseline occurred in 21% (grade 3 or 4, 6%) and 40% (grade 3 or 4, 4.2%) of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials.
Nephrotoxicity, specifically increase serum creatinine level, that worsened from baseline occurred in 15% and 31% of patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials.
Hypophosphatemia/decreased phosphate level (18% and 40%; grade 3 or 4, 6% and 6%) and hypocalcemia/decreased corrected calcium level (14% and 33%; grade 3 or 4, 0.6% and 0%) that worsened from baseline occurred in patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Hypokalemia/decreased potassium level that worsened from baseline was reported in 11% of patients with previously treated chronic phase Ph+ CML. Hyperkalemia/increased potassium level that worsened from baseline occurred in 48% (grade 3 or 4, 2.1%) of patients with chronic phase Ph+ CML with the T315I mutation.
Elevated hepatic enzymes including increased ALT (26% and 48%; grade 3 or 4, 0.6% and 6%), AST (21% and 35%; grade 3 or 4, 1.9% and 2.1%), and alkaline phosphatase (13% and 13%) levels and hyperbilirubinemia (12% and 23%) that worsened from baseline occurred in patients with previously treated chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) who received asciminib 40 mg twice daily (n = 156) and chronic phase Ph+ CML with the T315I mutation who received asciminib 200 mg twice daily (n = 48), respectively, in 2 clinical trials. Increased alkaline phosphatase level was reported in 13% of patients with chronic phase Ph+ CML with the T315I mutation.
Hematologic toxicity has been reported with asciminib therapy. Monitor patients for signs and symptoms of myelosuppression (e.g., unusual bleeding, infection). Obtain complete blood counts every 2 weeks for the first 3 months of treatment and then monthly thereafter or as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe neutropenia or thrombocytopenia.
Pancreatic toxicity has been reported with asciminib therapy; patients with a history of pancreatitis may be at increased risk. Monitor patients for signs and symptoms of pancreatic toxicity. Obtain serum amylase and lipase levels monthly or as clinically indicated. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop elevated pancreatic enzymes.
Hypertension has been reported with asciminib therapy. Monitor patients for signs of hypertension (e.g., blood pressure); manage patients who develop hypertension per standard clinical guidelines. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe hypertension.
Cardiovascular toxicity (e.g., ischemic cardiac and central nervous system conditions, arterial thrombotic and embolic conditions, cardiac arrhythmias, heart failure) has been reported with asciminib therapy. Monitor patients with a history of cardiac disease or cardiac risk factors because they may be at increased risk for cardiotoxicity. Therapy interruption, a dosage adjustment, or discontinuation may be necessary in patients who develop severe cardiovascular toxicity.
Asciminib may cause fetal harm in pregnant women based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid pregnancy while taking asciminib. Patients who become pregnant while receiving asciminib should be apprised of the potential hazard to the fetus. Embryo-fetal toxicity (e.g., increased resorptions/post implantation loss, cleft palate, anasarca, cardiac abnormalities and malformations, increased fetal weight due to increased ossification, and urinary tract and skeletal variations) occurred in the offspring of rats and rabbits when asciminib was administered during organogenesis.
Counsel patients about the reproductive risk and contraception requirements during asciminib treatment. Pregnancy testing should be performed prior to starting asciminib in female patients of reproductive potential. These patients should avoid pregnancy and use effective contraception during and for 1 week after the last asciminib dose. Women who become pregnant while receiving asciminib should be apprised of the potential hazard to the fetus. Infertility may occur with asciminib use in females based on animal data. It is not known whether fertility effects are reversible.
Due to the risk of serious adverse reactions in breast-fed children, women should discontinue breast-feeding during asciminib therapy and for 1 week after the last dose. It is not known if asciminib is secreted in human milk or if it has effects on the breast-fed child or on milk production.
For the treatment of chronic myelogenous leukemia (CML):
NOTE: Asciminib has been designated by the FDA as an orphan drug for the treatment of CML.
-for the treatment of chronic phase Philadelphia chromosome-positive CML (Ph+ CML) with the T315I mutation:
Oral dosage:
Adults: 200 mg orally twice daily (approximately 12 hours apart) until loss of response (treatment failure) or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, a dosage reduction, or permanent discontinuation may be necessary in patients who develop toxicity. A major molecular response (MMR) by week 24 was achieved in 42% of patients with chronic phase Ph+ CML with a T315I mutation (n = 45) who received asciminib in a phase 1 trial (CABL001X2101 trial). Additionally, 49% of patients achieved a MMR by week 96. The median duration of treatment was 108 (range, 2 to 215) weeks.
-for the treatment of chronic phase Ph+ CML in patients who had previously received 2 or more tyrosine kinase inhibitors:
Oral dosage:
Adults: 80 mg orally once daily OR 40 mg orally twice daily (approximately 12 hours apart) until loss of response (treatment failure) or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, a dosage reduction, or permanent discontinuation may be necessary in patients who develop toxicity. A major molecular response (MMR) by week 24 was achieved in 25.5% of patients with chronic phase Ph+ CML resistant or intolerant to 2 or more tyrosine kinase inhibitors who received asciminib 40 mg PO twice daily (n = 157) compared with 13.2% of patients who received bosutinib 500 mg PO once daily (n = 76) in a randomized (2:1) phase 3 trial (ASCEMBL trial). The 24-week MMR risk difference significantly favored asciminib treatment (12.3%; 95% CI, 2.1% to 22.5%); the odds ratio also favored asciminib (OR = 2.38; 95% CI, 1.06 to 5.35) in a multivariate analysis. At a median follow-up time of 2.3 years, the MMR rate continued to be significantly higher at week 96 in patients who received asciminib compared with bosutinib (37.6% vs. 15.8%; risk difference, 21.74%; 95% CI, 10.53 to 32.95; p = 0.001) in the ASCEMBL trial. The median duration of asciminib treatment was 23.7 (range, 0 to 46.2) months.
Therapeutic Drug Monitoring:
Dosage Guidance for Treatment-Related Toxicity
Dosage Adjustments
Chronic phase Ph+ CML with the T315I mutation:
First reduction: 160 mg PO twice daily.
Subsequent reductions: Permanently discontinue therapy in patients unable to tolerate 160 mg PO twice daily.
Previously treated chronic phase Ph+ CML:
First reduction: once-daily dosing, 40 mg PO once daily; twice-daily dosing, 20 mg PO twice daily.
Subsequent reductions: Permanently discontinue therapy in patients unable to tolerate 40 mg PO once daily or 20 mg PO twice daily.
Hematologic Toxicity
Absolute neutrophil count (ANC) less than 1 X 109 cells/L OR platelet count less than 50 X 109 cells/L: Hold asciminib therapy until toxicity is resolved to ANC of 1 X 109 cells/L or more or platelet count of 50 X 109 cells/L or more. If the toxicity resolves within 2 weeks, resume therapy at the starting dosage. If the toxicity resolves after more than 2 weeks, resume therapy at a reduced dosage. For recurrent severe myelosuppression, resume at a reduced dosage after toxicity resolves.
Pancreatic Toxicity
Elevated amylase and/or lipase level to more than 2 times the ULN and asymptomatic: Hold asciminib therapy until toxicity is resolved to amylase or lipase level less than 1.5 times the ULN. If the toxicity resolves, resume therapy at a reduced dosage; permanently discontinue therapy if the toxicity recurs at a reduced dosage. If the toxicity does not resolve, permanently discontinue therapy and evaluate the patient for pancreatitis.
Elevated amylase and lipase levels and symptomatic (e.g., abdominal pain): Hold asciminib therapy and evaluate the patient for pancreatitis.
Other Non-Hematologic Toxicity (including hypertension, hypersensitivity, and cardiovascular toxicity)
Grade 3 or higher toxicity: Hold asciminib therapy until toxicity recovers to grade 1 or less. If the toxicity resolves, resume therapy at a reduced dosage. If the toxicity does not resolve, permanently discontinue therapy.
Maximum Dosage Limits:
-Adults
80 mg/day PO for previously treated chronic phase Ph+ CML; 400 mg/day PO for chronic phase Ph+ CML with the T315I mutation.
-Geriatric
80 mg/day PO for previously treated chronic phase Ph+ CML; 400 mg/day PO for chronic phase Ph+ CML with the T315I mutation.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
An asciminib dosage adjustment is not necessary in patients with mild (total bilirubin level at or below the ULN and AST level greater than the ULN OR total bilirubin level of 1 to 1.5 times the ULN and any AST level) to severe (total bilirubin level more than 3 times the ULN and any AST level) hepatic impairment.
Patients with Renal Impairment Dosing
An asciminib dosage adjustment is not necessary in patients with mild to severe renal impairment (estimated glomerular filtration rate of 15 to 89 mL/min/1.73 m2).
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with asciminib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and asciminib is a BCRP inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with asciminib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Asciminib is a weak inhibitor of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like asciminib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If asciminib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with adagrasib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If asciminib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alpelisib: (Major) Avoid coadministration of alpelisib with asciminib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and asciminib is a BCRP inhibitor.
Alprazolam: (Major) Avoid coadministration of alprazolam and asciminib due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with asciminib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a BCRP and OATP1B1/3 substrate; asciminib is a BCRP and OATP1B1/3 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with clarithromycin is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin increased asciminib exposure by 36%.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of asciminib. Patients receiving both a CYP2D6 inhibitor plus asciminib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; asciminib is a weak CYP3A inhibitor.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like asciminib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If asciminib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with atazanavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with atazanavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with asciminib. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and asciminib is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a BCRP and OATP1B1/3 substrate; asciminib is a BCRP and OATP1B1/3 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Consider a reduced dose of benzhydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of benzhydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to benzhydrocodone.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Bosentan: (Moderate) Monitor for an increase in bosentan-related adverse reactions if concomitant use of asciminib is necessary. Concomitant use may increase bosentan exposure. Administration of bosentan with both asciminib 200 mg twice daily and a strong or moderate CYP3A inhibitor is not recommended. Bosentan is a CYP2C9 and CYP3A substrate; asciminib is a moderate CYP2C9 inhibitor at a dose of 200 mg twice daily, and a weak CYP2C9 inhibitor at doses less than 200 mg twice daily.
Brincidofovir: (Moderate) Postpone the administration of asciminib for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and asciminib is necessary. Brincidofovir is an OATP1B1/3 substrate and asciminib is an OATP1B1/3 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1/3 inhibitor.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with asciminib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and asciminib is a CYP2C9 inhibitor.
Buprenorphine: (Moderate) Concomitant use of buprenorphine and asciminib can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when asciminib is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping asciminib, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If asciminib is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and asciminib is a CYP3A inhibitor.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine and asciminib can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when asciminib is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping asciminib, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If asciminib is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and asciminib is a CYP3A inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of asciminib; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and asciminib is a CYP3A inhibitor.
Carvedilol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of carvedilol with asciminib 200 mg twice daily is necessary. Carvedilol is a CYP2C9 substrate and asciminib 200 mg twice daily is a CYP2C9 inhibitor. Concomitant use may enhance the beta-blocking properties of carvedilol resulting in further slowing of the heart rate or cardiac conduction. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with asciminib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of asciminib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Ceritinib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ceritinib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Chloramphenicol: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with chloramphenicol is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with clarithromycin is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin increased asciminib exposure by 36%.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with asciminib and monitor for adverse reactions. If asciminib is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A. Asciminib is a weak CYP3A inhibitor.
Cobicistat: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Codeine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with asciminib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of asciminib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If asciminib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Asciminib is a weak inhibitor of CYP3A.
Colchicine: (Major) Avoid concomitant use of colchicine and asciminib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and asciminib is a P-gp inhibitor.
Cyclosporine: (Moderate) Closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with asciminib is necessary. The dose of cyclosporine may need to be adjusted. Concurrent use may increase cyclosporine exposure causing an increased risk for cyclosporine-related adverse events. Cyclosporine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Darunavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with darunavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with darunavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with darunavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Delavirdine: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with delavirdine is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with asciminib is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A substrate and asciminib is a CYP3A inhibitor.
Disopyramide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with asciminib is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with asciminib is necessary as concurrent use may increase dofetilide exposure. Asciminib is a weak CYP3A inhibitor. Dofetilide is a minor CYP3A substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A inhibitors may increase the risk of arrhythmia (torsade de pointes).
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with asciminib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and asciminib is a BCRP inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with asciminib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and asciminib is a BCRP inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with asciminib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and asciminib is a BCRP inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Dronabinol: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with asciminib 200 mg twice daily. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP2C9 substrate; asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Elagolix: (Contraindicated) Coadministration of elagolix with asciminib is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and asciminib is a strong OATP1B1 inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Coadministration of elagolix with asciminib is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and asciminib is a strong OATP1B1 inhibitor.
Elbasvir; Grazoprevir: (Contraindicated) Concomitant use of grazoprevir and asciminib is contraindicated due to the potential for increased grazoprevir exposure. Grazoprevir is a substrate of OATP1B1/3; asciminib is an inhibitor of OATP1B1/3.
Eliglustat: (Major) Coadministration of eliglustat and asciminib is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Asciminib is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Eluxadoline: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with asciminib. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and asciminib is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with cobicistat is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and asciminib 200 mg bid due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and asciminib 200 mg bid is a moderate CYP2C9 inhibitor.
Etravirine: (Moderate) Monitor for an increase in etravirine-related adverse reactions if concomitant use of asciminib 200 mg twice daily is necessary. Etravirine is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
Felodipine: (Moderate) Concurrent use of felodipine and asciminib should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A substrate and asciminib is a weak CYP3A inhibitor. Concurrent use of another weak CYP3A inhibitor increased felodipine AUC and Cmax by approximately 50%.
Fentanyl: (Minor) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If asciminib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or asciminib; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including asciminib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Fluvastatin: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; asciminib is an inhibitor of OATP1B3.
Food: (Major) Advise patients to avoid cannabis use during asciminib treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoid delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP2C9 substrates and asciminib is a CYP2C9 inhibitor.
Glecaprevir; Pibrentasvir: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase glecaprevir exposure. Glecaprevir is a BCRP and OATP1B1/3 substrate; asciminib is a BCRP and OATP1B1/3 inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of asciminib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of BCRP and asciminib is a BCRP inhibitor.
Glimepiride: (Moderate) Monitor for an increase in glimepiride-related adverse reactions, such as hypoglycemia, if coadministration with asciminib 200 mg twice daily is necessary. Concomitant use may increase glimepiride exposure. Glimepiride is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Glipizide: (Moderate) Monitor for an increase in glipizide-related adverse reactions, such as hypoglycemia, if coadministration with asciminib 200 mg twice daily is necessary. Concomitant use may increase glipizide exposure. Glipizide is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Glipizide; Metformin: (Moderate) Monitor for an increase in glipizide-related adverse reactions, such as hypoglycemia, if coadministration with asciminib 200 mg twice daily is necessary. Concomitant use may increase glipizide exposure. Glipizide is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Glyburide: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with asciminib is necessary. Concomitant use may increase glyburide exposure. Glyburide is a CYP2C9 and OATP1B1/3 substrate and asciminib is a CYP2C9 and OATP1B1/3 inhibitor.
Glyburide; Metformin: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with asciminib is necessary. Concomitant use may increase glyburide exposure. Glyburide is a CYP2C9 and OATP1B1/3 substrate and asciminib is a CYP2C9 and OATP1B1/3 inhibitor.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during asciminib treatment due to the risk of increased asciminib exposure and adverse reactions. Asciminib is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like asciminib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If asciminib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like asciminib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If asciminib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with idelalisib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Indinavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with indinavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor.
Isradipine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with asciminib is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Itraconazole: (Major) Avoid concurrent use of asciminib with itraconazole oral solution containing hydroxypropyl-beta-cyclodextrin as asciminib exposure may decrease which may reduce its efficacy; an interaction is not expected with other formulations of itraconazole. Coadministration of multiple doses of itraconazole oral solution containing hydroxypropyl-beta-cyclodextrin with a single 40-mg asciminib dose decreased asciminib exposure by 40%.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of asciminib is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Ketoconazole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ketoconazole is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with clarithromycin is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin increased asciminib exposure by 36%.
Lemborexant: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with asciminib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; asciminib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Letermovir: (Moderate) Monitor for an increase in letermovir-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase letermovir exposure. Letermovir is a substrate of OATP1B1/3; asciminib is an OATP1B1/3 inhibitor.
Levoketoconazole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ketoconazole is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Lomitapide: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with asciminib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Asciminib is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and asciminib; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing asciminib. Additionally, closely monitor for asciminib-related adverse reactions if using asciminib 200 mg twice daily with lonafarnib as asciminib exposure may increase. Lonafarnib is a CYP2C9 and CYP3A substrate and strong CYP3A inhibitor; asciminib is a CYP3A substrate and CYP2C9 and CYP3A inhibitor.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with asciminib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with asciminib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ritonavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Losartan: (Moderate) Closely monitor blood pressure during coadministration of losartan and asciminib at doses greater than or equal to 200 mg BID; adjust the dose of losartan as clinically appropriate. Concomitant use may decrease exposure to the active metabolite of losartan and decrease losartan efficacy. Losartan is a CYP2C9 substrate; asciminib at doses greater than or equal to 200 mg BID is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9 inhibitor in two pharmacokinetic studies with healthy volunteers decreased concentrations of the active metabolite of losartan by 30% to 56%.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure during coadministration of losartan and asciminib at doses greater than or equal to 200 mg BID; adjust the dose of losartan as clinically appropriate. Concomitant use may decrease exposure to the active metabolite of losartan and decrease losartan efficacy. Losartan is a CYP2C9 substrate; asciminib at doses greater than or equal to 200 mg BID is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9 inhibitor in two pharmacokinetic studies with healthy volunteers decreased concentrations of the active metabolite of losartan by 30% to 56%.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with asciminib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and asciminib is a weak CYP3A inhibitor.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with asciminib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and asciminib is a CYP2C9 inhibitor.
Meperidine: (Moderate) Consider a reduced dose of meperidine with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, meperidine plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to meperidine. Meperidine is a substrate of CYP3A and asciminib is a weak CYP3A inhibitor. Concomitant use with asciminib can increase meperidine exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of meperidine.
Metformin; Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with asciminib is necessary. Repaglinide is a CYP2C8 and CYP3A substrate and asciminib is a weak CYP2C8 and CYP3A inhibitor. Coadministration of repaglinide with asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily increased the exposure of repaglinide by 8%, 12% and 42%, respectively.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; asciminib is a CYP2C9 and CYP3A inhibitor. Concomitant use with asciminib can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Midazolam: (Moderate) Use caution when midazolam is coadministered with asciminib. Concurrent use may increase midazolam exposure leading to prolonged sedation. Midazolam is a sensitive CYP3A substrate and asciminib is a weak CYP3A inhibitor. Coadministration of midazolam with asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily increased the exposure of midazolam by 28%, 24%, and 88%, respectively.
Mifepristone: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with mifepristone is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Momelotinib: (Moderate) Monitor for an increase in momelotinib-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase momelotinib exposure. Momelotinib is an OATP1B1/3 substrate; asciminib is an OATP1B1/3 inhibitor. Coadministration with another OATP1B1/1B3 inhibitor increased momelotinib exposure by 57%; exposure of its active M21 metabolite increased by 12%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of asciminib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and asciminib is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and asciminib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and asciminib is a weak CYP3A and P-gp inhibitor.
Nateglinide: (Moderate) Monitor for an increase in nateglinide-related adverse effects, such as hypoglycemia, if concomitant use with asciminib is necessary; a nateglinide dosage reduction may be required. Concomitant use may increase nateglinide exposure. Nateglinide is a CYP2C9 substrate and asciminib is a CYP2C9 inhibitor.
Nefazodone: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with nefazodone is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with nelfinavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor.
Nimodipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with asciminib is necessary. Concurrent use may increase nimodipine exposure. Nimodipine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Nintedanib: (Moderate) Monitor for nintedanib-related adverse reactions if concomitant use of asciminib is necessary. Concomitant use may increase nintedanib exposure. Nintedanib is a P-gp substrate, and a minor substrate of CYP3A and asciminib is a dual P-gp and CYP3A inhibitor. Coadministration with another dual P-gp and CYP3A inhibitor increased nintedanib AUC by 60%.
Nirmatrelvir; Ritonavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ritonavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with asciminib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and asciminib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like asciminib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If asciminib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of asciminib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and asciminib is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Pazopanib: (Major) Avoid coadministration of pazopanib and asciminib due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; asciminib is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP.
Pimozide: (Major) Avoid concomitant use of pimozide and asciminib. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and asciminib is a weak CYP3A inhibitor.
Pioglitazone; Glimepiride: (Moderate) Monitor for an increase in glimepiride-related adverse reactions, such as hypoglycemia, if coadministration with asciminib 200 mg twice daily is necessary. Concomitant use may increase glimepiride exposure. Glimepiride is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
Posaconazole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with posaconazole is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Pralsetinib: (Major) Avoid concomitant use of asciminib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pravastatin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; asciminib is an OATP1B1/3 inhibitor.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and asciminib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and asciminib is a P-gp inhibitor.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with asciminib; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and asciminib with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A and CYP2D6 substrate; asciminib is a weak CYP3A inhibitor.
Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with asciminib is necessary. Repaglinide is a CYP2C8 and CYP3A substrate and asciminib is a weak CYP2C8 and CYP3A inhibitor. Coadministration of repaglinide with asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily increased the exposure of repaglinide by 8%, 12% and 42%, respectively.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with asciminib due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and asciminib is a P-gp inhibitor.
Resmetirom: (Major) Avoid concomitant use of resmetirom and asciminib due to the risk for increased resmetirom exposure which may increase the risk for resmetirom-related adverse effects. Resmetirom is an OATP1B1/3 substrate and asciminib is an OATP1B1/3 inhibitor.
Revefenacin: (Major) Avoid concomitant use of revefenacin and asciminib. Concomitant use may increase exposure to the active metabolite of revefenacin and the risk for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1/3; asciminib is an inhibitor of OATP1B1/3.
Ribociclib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ribociclib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ribociclib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Ritonavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ritonavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with asciminib; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 and CYP2C9 substrate and asciminib is a CYP2C8 and CYP2C9 inhibitor. Coadministration of rosiglitazone with asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily increased the exposure of rosiglitazone by 20%, 24% and 66%, respectively.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with asciminib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP and OATP1B1/3 substrate and asciminib is a BCRP and OATP1B1/3 inhibitor.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with asciminib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP and OATP1B1/3 substrate and asciminib is a BCRP and OATP1B1/3 inhibitor.
Saquinavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with saquinavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with asciminib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
Siponimod: (Moderate) Concomitant use of siponimod and asciminib 200 mg twice daily may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate or strong CYP3A inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A substrate; asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9/CYP3A dual inhibitor led to a 2-fold increase in the AUC of siponimod. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of asciminib. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and asciminib is a weak CYP3A and P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Avoid coadministration of sodium phenylbutyrate; taurursodiol and asciminib. Concomitant use may increase plasma concentrations of sodium phenylbutyrate; taurursodiol. Sodium phenylbutyrate; taurursodiol is an OATP1B3 substrate and asciminib is an OATP1B3 inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of voxilaprevir and asciminib. Concomitant use may increase voxilaprevir exposure and the risk of voxilaprevir-related adverse reactions. Voxilaprevir is a substrate of OATP1B1/3; asciminib is an OATP1B1/3 inhibitor.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if asciminib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of asciminib is necessary. If asciminib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like asciminib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If asciminib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with asciminib is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; asciminib is a weak CYP3A inhibitor.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of asciminib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate and asciminib is a P-gp and BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and asciminib is a BCRP inhibitor.
Terbinafine: (Moderate) Monitor for an increase in terbinafine-related adverse reactions if coadministration with asciminib is necessary. Terbinafine is a CYP2C9 and CYP3A substrate; asciminib is a dual CYP2C9 and CYP3A inhibitor. Coadministration with a moderate CYP2C9 and CYP3A inhibitor increased the Cmax and AUC of terbinafine by 52% and 69%, respectively.
Tipranavir: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with tipranavir is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor.
Topotecan: (Major) Avoid coadministration of asciminib with oral topotecan due to increased topotecan exposure; asciminib may be administered with intravenous topotecan. Coadministration increases the risk of topotecan-related adverse reactions. Oral topotecan is a BCRP substrate and asciminib is a BCRP inhibitor.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with asciminib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of asciminib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with asciminib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of asciminib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with asciminib and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Tucatinib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with tucatinib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with asciminib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A and BCRP substrate; asciminib is a weak CYP3A and BCRP inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with asciminib is necessary. Vinorelbine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with clarithromycin is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin increased asciminib exposure by 36%.
Voriconazole: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with voriconazole is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with asciminib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The active metabolite of warfarin, the S-enantiomer, is a CYP2C9 substrate and asciminib is a CYP2C9 inhibitor. Coadministration of warfarin with asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily increased the exposure of S-warfarin by 41%,52% and 314%, respectively. Additionally, the R-enantiomer of warfarin is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zafirlukast: (Moderate) Monitor for an increase in zafirlukast-related adverse reactions if concomitant use of asciminib 200 mg twice daily is necessary. Concomitant use may increase zafirlukast exposure. Zafirlukast is a CYP2C9 substrate and asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9 inhibitor increased the exposure of zafirlukast by approximately 58%. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Zavegepant: (Major) Avoid concomitant use of zavegepant and asciminib. Concomitant use may increase zavegepant exposure and the risk for zavegepant-related adverse effects. Zavegepant is an OATP1B3 substrate and asciminib is an OATP1B3 inhibitor. Concomitant use with another OATP1B3 inhibitor increased zavegepant overall exposure by 2.3-fold.
Asciminib is an oral ABL/BCR-ABL1 tyrosine kinase inhibitor (TKI) specifically targeting the ABL myristoyl pocket (STAMP). It inhibits the ABL1 kinase activity of the BCR-ABL1 fusion protein by binding to the ABL myristoyl pocket. Asciminib has demonstrated activity against wild-type and some mutant forms of BCR-ABL including T315I. By binding in the myristoyl pocket, asciminib mimics myristate and stabilizes the inactive state of ABL kinase. Asciminib inhibits BCR-ABL1 proliferation in leukemia cell lines at IC50 values between 1 and 25 nanomolar. Its anti-proliferative activity is reduced by 10-fold on T315I mutant (mean, IC50 concentration,7.64 nanomolar) compared with wild-type (mean, IC50 concentration, 0.61 nanomolar) BCR-ABL1-expressing cells. Asciminib demonstrated resistance to overexpression of ABCB1/ABCG2 and p-STAT5 in human BCR-ABL1 cell lines.
Asciminib is administered orally. It is 97% bound to plasma proteins in vitro. The mean apparent steady-state volume of distribution is 151 L (coefficient of variation (CV), 135%); asciminib is the main component in plasma (93% of the dose). At a dosage of 40 mg twice daily or 80 mg once daily, the terminal elimination half-life is 5.5 hours (CV, 38%) and the apparent clearance is 6.7 L/hour (CV, 48%). At a dosage of 200 mg twice daily, the terminal elimination half-life is 9 hours (CV, 33%) and the apparent clearance is 4.1 L/hour (CV, 38%). Asciminib is metabolized by the CYP3A4 isoenzyme and by UGT2B7-and UGT2B17-mediated glucuronidation; elimination occurs by biliary secretion via the breast cancer resistant protein (BCRP). Following a single oral 80-mg dose of radiolabeled asciminib, 80% of the total radioactivity was recovered in the feces (unchanged, 57%) and 11% was recovered in the urine (unchanged, 2.5%).
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C8, CYP2C9, P-gp, BCRP, OATP1B1
Asciminib is substrate and a weak inhibitor of CYP3A4; it is also a weak CYP2C8 inhibitor, a P-glycoprotein (P-gp) inhibitor, a weak CYP2C9 inhibitor at 40 mg twice daily or 80 mg once daily dosing, and a moderate CYP2C9 inhibitor at 200 mg twice daily dosing. Although asciminib is a P-gp substrate in vitro, no clinically relevant pharmacokinetic differences were observed when asciminib was administered with a P-gp inhibitor (quinidine). In vitro, asciminib is a reversible inhibitor UGT1A1 (at 80 mg/day and 200 mg twice daily) and CYP2C19 (at 200 mg twice daily); it is also a substrate of BCRP and an inhibitor of BCRP, OATP1B1, OATP1B3, and OCT1. Although the effect of concomitant use of asciminib with OATP1B and BCRP substrates has not been established in clinical studies, concomitant use may increase the Cmax and AUC values of OATP1B and BCRP substrates based on a mechanistic understanding of the elimination of asciminib and its in vitro inhibitory potential. Asciminib may increase the exposure of OATP1B and BCRP substrates in a dose dependent manner.
-Route-Specific Pharmacokinetics
Oral Route
At a dosage of 40 mg twice daily, the steady-state asciminib Cmax and AUC(0 to 12h) values were 793 nanograms/mL (coefficient of variation (CV), 49%) and 5,262 nanograms x hour/mL (CV, 48%), respectively; the accumulation ratio was 1.65. At a dosage of 80 mg once daily, the steady-state asciminib Cmax and AUC(0 to 24h) values were 1,781 nanograms/mL (CV, 23%) and 15,112 nanograms x hour/mL (CV, 28%), respectively; the accumulation ratio was 1.3. At a dosage of 200 mg twice daily, the steady-state asciminib Cmax and AUC(0 to 12h) values were 5,642 nanograms/mL (CV, 40%) and 37,547 nanograms x hour/mL (CV, 41%), respectively; the accumulation ratio was 1.92. Steady state was achieved within 3 days. The median Tmax is 2.5 hours (range, 2 to 3 hours). Asciminib exhibits slightly more than dose-proportional increases in steady-state Cmax and AUC values over a dose range of 10 to 200 mg given once or twice daily.
Effects of Food: The AUC and Cmax values decreased by 62% and 68%, respectively, when asciminib was administered with a high-fat (1,000 calories with 50% from fat) and by 30% and 35%, respectively, when asciminib was administered with a low-fat meal (400 calories with 25% from fat) compared with fasting conditions.
-Special Populations
Hepatic Impairment
Mild (total bilirubin level at or below the ULN and AST level greater than the ULN OR total bilirubin level of 1 to 1.5 times the ULN and any AST level) or moderate (total bilirubin level of 1.5 to 3 times the ULN and any AST level) hepatic impairment does not have a clinically significant impact on the pharmacokinetic parameters of asciminib. Following a single 40-mg dose of asciminib, the Cmax and AUC(inf) values were increased by 4% and 33%, respectively, in subjects with severe hepatic impairment (total bilirubin level more than 3 times the ULN and any AST level) compared with subjects who had normal hepatic function.
Renal Impairment
Mild to moderate renal impairment (estimated glomerular filtration rate (eGFR) of 30 to 89 mL/min/1.73 m2) does not have a clinically significant impact on the pharmacokinetic parameters of asciminib. Following a single 40-mg dose of asciminib, the Cmax and AUC(inf) values were increased by 6% and 57%, respectively, in subjects with severe renal impairment (eGFR of 14 to less than 30 mL/min/1.73 m2) who were not receiving dialysis compared with subjects who had normal renal function.
Geriatric
Age (range, 20 to 88 years) does not have a clinically significant impact on the pharmacokinetic parameters of asciminib.
Gender Differences
Sex does not have a clinically significant impact on the pharmacokinetic parameters of asciminib.
Ethnic Differences
Race (Asian 20%, White 70%, Black/African American 4%) does not have a clinically significant impact on the pharmacokinetic parameters of asciminib.
Obesity
Body weight (range, 42 kg to 184 kg) does not have a clinically significant impact on the pharmacokinetic parameters of asciminib.