Asciminib

Asciminib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra

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Overview

Asciminib is a kinase inhibitor that is FDA approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia with disease that meets certain criteria. Common adverse reactions include include fatigue, nausea, diarrhea, rash, musculoskeletal pain, and upper respiratory tract infections.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

For Patients with Ph+ CML-CP, previously treated with two or more TKIs: Recommended dosage is 80 mg taken once a day orally or 40 mg twice a day in 12 hour intervals orally.

For Patients with Ph+ CML-CP with the T315I mutation: Recommended dosage is 200 mg twice a day in 12 hour intervals orally.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Asciminib in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Asciminib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Asciminib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Asciminib in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Asciminib in pediatric patients.

Contraindications

There are no contraindications associated with Asciminib.

Warnings

•Myelosuppression: Studies conducted show evidence of thrombocytopenia, neutropenia, and anemia. Thrombocytopenia was found in 28% of patients taking Asciminib. Of those patients, Grade 3 thrombocytopenia occurred in 7% of patients and Grade 4 thrombocytopenia occurred in 12% of patients. Neutropenia was found in 19% of patients taking Asciminib. Of those patients, Grade 3 neutropenia occurred in 8% of patients and Grade 4 neutropenia occurred in 8% of patients. Anemia was found in 13% of patients taking Asciminib. Of those patients, Grade 3 anemia occurred in 5% of patients. To monitor symptoms, blood counts should be conducted every 2 weeks of initial start to monthly checks after 3 months of treatment. Alter dosage or permanently discontinue Asciminib based on severity of symptoms.

•Pancreatic Toxicity: Serum lipase and amylase should be monitored monthly in patients using Asciminib and frequently in patients that have a history of pancreatitis. Studies showed Pancreatitis in 2.5% of patients with Grade 3 Pancreatitis occurring in 1.1% of patients. Increase in lipase and amylase occurred in 21% of patients. Of those patients, Grade 3 pancreatic enzyme elevation occurred in 10% of patients and Grade 4 pancreatic enzyme elevation occurred in 2.2% of patients. Alter or discontinue the use of Asciminib when levels of serum lipase and amylase change.

•Hypertension: Hypertension should be monitored and treated appropriately. Studies conducted show that hypertension occurred in 19% patients. Of those patients, Grade 3 hypertension was found in 9% of patients and Grade 4 hypertension was found in 0.3% of patients. Advise patients who have symptoms of Grade 3 and higher hypertensions should either reduce, temporarily withold, or permanently discontinue the use of Asciminib depending on the severity of the symptoms.

•Hypersensitivity: Hypersensitivity including rash, edema, and bronchospasm have been reported in patients using Asciminib. Studies conducted show that hypersensitivity occurred in 32% patients. Of those patients, Grade 3 or Grade 4 hypersensitivity was found in 1.7% of patients and. Patients with symptoms of Grade 3 and higher hypersensitivity should either reduce, temporarily withold, or permanently discontinue the use of Asciminib depending on the severity of the symptoms.

•Cardiovascular Toxicity: Cardiovascular toxicity including ischemic cardiac, arterial thrombotic and embolic conditions have been reported in patients using Asciminib. Studies conducted show that cardiovascular toxicity occurred in 13% patients while 2.2% of patients had cardiac failure. Of those patients, Grade 3 cardiovascular toxicity occurred in 3.4% of patients and Grade 3 cardiac failure occurred in 1.1% of patients. The study also showed Grade 4 cardiovascular toxicity occurred in 0.6% of patients. Monitor patients regularly who have a history of cardiovascular risks when taking Asciminib. Patients with symptoms of Grade 3 and higher cardiovascular toxicity should either reduce, temporarily withold, or permanently discontinue the use of Asciminib depending on the severity of the symptoms.

•Embryo-Fetal Toxicity: Based on animal data, Asciminib potentially can cause harm to females fetus during pregnancy. Animal studies show mortality and malformations in rats and rabbits occurred during organogenesis. Advise females about potential risks to a fetus when taking Asciminib. Advise females of reproductive potential to use effective contraception during treatment with Asciminib and for at least 1 week after the last dose.

Adverse Reactions

Clinical Trials Experience

Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Asciminib has been evaluated for safety in 356 patients who were observed in one of two clinical trial with one trial including patients with Ph+ CML-CP, previously treated with two or more TKIs and the other trial including patients with Ph+ CML-CP with the T315I mutation. Both trials are discussed below that compared Asciminib to Bosutinib for a median duration of 89 weeks.

Patients with Ph+ CML-CP, previously treated with two or more TKIs: 15% of patients taking Asciminib received adverse reactions such as pyrexia (1.9%), cardiac failure congestive (1.3%), thrombocytopenia (1.3%), and urinary tract infection (1.3%). Studies showed that 7% of patients who had adverse reactions had to permanently discontinue Asciminib with reactions including thrombocytopenia (3.2%) and neutropenia (2.6%). 38% of patients had interruptions in their dosage due to adverse reactions that included thrombocytopenia (19%) and neutropenia (18%). Dosage reductions occurred due to adverse reactions in 38% of patients that showed thrombocytopenia (19%) and neutropenia (18%). Upper respiratory tract infections and musculoskeletal pain were the most common adverse reactions (≥ 20%) in patients.

Table 3 shows the overall adverse reactions in Patients with Ph+ CML-CP, previously treated with two or more TKIs taking Asciminib compared to Bosutinib.

Insert Table 3

Patients with Ph+ CML-CP with the T315I mutation: 23% of the patients taking Asciminib displayed adverse reactions such as abdominal pain (4.2%), vomiting (4.2%), pneumonia (4.2%), musculoskeletal pain (2.1%), headache (2.1%), hemorrhage (2.1%), constipation (2.1%), arrhythmia (2.1%), and pleural effusion (2.1%). Studies showed that 10% of patients who had adverse reactions had to permanently discontinue Asciminib with reactions including pancreatic enzymes increase (2.1%). 31% of patients had interruptions in their dosage due to adverse reactions that included thrombocytopenia (19%) and pancreatic enzymes increase (17%). Dosage reductions occurred due to adverse reactions in 23% of patients that showed pancreatic enzymes increase (10%), abdominal pain (4.2%), anemia (2.1%), blood bilirubin increase (2.1%), dizziness (2.1%), fatigue (2.1%), hepatic enzymes increase (2.1%), musculoskeletal pain (2.1%), nausea (2.1%), neutropenia (2.1%), pruritus (2.1%), and thrombocytopenia (2.1%). Musculoskeletal pain, fatigue, nausea, rash, and diarrhea were the most common adverse reactions (≥ 20%) in patients.

Table 5 shows the overall adverse reactions in Patients with Ph+ CML-CP with the T315I mutation taking Asciminib compared to Bosutinib.

Insert Table 5

Postmarketing Experience

There is limited information about "Postmarketing Experiance" in the drug label.

Drug Interactions

•Strong CYP3A4 Inhibitors: Concomitant use of these drugs potentially increases the likelihood of adverse effects in patients because of the inhibitory effect that Asciminib plays on CYP3A4.

•Itraconazole Oral Use containing Hydroxypropyl-β-cyclodextrin: Concomitant use of these drugs may decrease Asciminib efficacy in patients.

•Certain CYP3A4: Concomitant use of these drugs potentially increases the likelihood of adverse effects in patients.

•CYP2C9 Substrates: Concomitant use of these drugs potentially increases the likelihood of adverse effects in patients because of the inhibitory effect that Asciminib plays on CYP2C9.

•Certain P-gp Substrates: Concomitant use of these drugs potentially increases the likelihood of adverse effects in patients because of the increase in plasma membrane concentration of these substrates.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Reproduction studies done on rats and rabbits at doses up to 600 mg/kg/day and 300 mg/kg/day, respectively, revealed both maternal toxicity at the highest doses and malformations in different areas of the body. These studies display the potential harms and risks in the embryo of pregnant woman when taking Asciminib.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Asciminib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Asciminib during labor and delivery.

Nursing Mothers

No data has been conducted on nursing in human when taking Asciminib. Based on studies done on rats and rabbits, it is recommended not to lactate when taking Asciminib.

Pediatric Use

Safety and effectiveness in pediatric populations have not been established.

Geriatic Use

Of the total number of subjects in the ASCEMBL clinical studies, around 19% of the patients were 65 years or older in age, and 2.6% were 75 years or older in age. In X2101 that tested patients with T315I mutation, around 33% of the patients were 65 years or older in age, and 8% were 75 years or older in age. No differences among young patients compared to patients 65 years or older in age were found when looking at safety and efficacy of Asciminib. More data is required to assess safety and efficacy between young patients and patients 75 year or older in age.

Gender

There is no FDA guidance on the use of Asciminib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Asciminib with respect to specific racial populations.

Renal Impairment

Patients with mild and severe renal impairment require no change to dosage usage.

Hepatic Impairment

Patients with mild and severe hepatic impairment require no change to dosage usage.

Females of Reproductive Potential and Males

Infertility can be impaired in females based on studies done on rats and rabbits. Asciminib has shown signs of harm in the embryo of pregnant women. There has been no effects recorded in males on their reproductive potential.

Immunocompromised Patients

There is no FDA guidance on the use of Asciminib with respect to immunocompromised populations.

Administration and Monitoring

Administration

Swallow Asciminib tablets whole. Do not chew, crush, or break tablets. Do not eat 2 hours before taking tablet and 1 hour after taking tablet. Follow recommended dosage as prescribed by a doctor.

Monitoring

There is limited information regarding Asciminib monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Asciminib and IV administrations.

Overdosage

There is limited information regarding Asciminib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Asciminib Pharmacology in the drug label.

Mechanism of Action

Asciminib is a tyrosine kinase inhibitor that has an inhibitory effect on the ABL1 kinase protein.

Structure

There is limited information regarding Asciminib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Asciminib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Asciminib Pharmacokinetics in the drug label.

Nonclinical Toxicology

No research has been conducted on the carcinogenicity when dealing with Asciminib. When looking at fertility, studies conducted on male rats have shown evidence of a decrease in sperm count and motility when dosed with 200 mg/kg/day of Asciminib. Studies on female mice showed evidence of decreased living embryos when dosed with 200 mg/kg/day of Asciminib. Mutagenicity studies have shown that Asciminib is not genotoxic.

Clinical Studies

Two clinical trials were conducted on Patients with Ph+ CML-CP, previously treated with two or more TKIs and Patients with Ph+ CML-CP with the T315I mutation.

Patients with Ph+ CML-CP, previously treated with two or more TKIs: The efficacy of Asciminib was tested on 233 patients that either received 40 mg of Asciminib twice daily or bosutinib 500 mg once daily. The patient population was largely Caucasian (75%), and included 52% women, and 19% were 65 years or older. Patients in the study took Asciminib for an average duration of 67 weeks and Bosutinib for an average duration 30 weeks. The results of the study are summarized in table 8. The study showed that MMR rate was at 29% for patients taking Asciminib and 13% for patients taking Bosutinib.

Insert Table 8

Patients with Ph+ CML-CP with the T315I mutation: The efficacy of Asciminib was tested on 45 patients that received 200 mg of Asciminib twice daily. The patient population was largely Caucasian (47%), and included 80% male, and 31% were 65 years or older. Patients in the study took Asciminib for an average duration of 108 weeks. The study showed MMR rate at 24 weeks (42%) and 96 weeks (49%) of the patients taking Asciminib.

How Supplied

Asciminib is supplied either as a 20 mg or 40 mg coated tablet. The 20 mg are "pale yellow, unscored, round, biconvex, with beveled edges, film-coated tablet". The 40 mg are "violet white, unscored, round, biconvex, with beveled edges, film-coated tablet".

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. To protect from moisture, store in original container.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Asciminib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Asciminib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Scemblix

Look-Alike Drug Names

There is limited information regarding Asciminib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.