asciminib hydrochloride: clinical use

Prescribing considerations

• Initiation should be supervised by a clinician experienced in diagnosing and treating CML.
• Confirm chronic-phase Philadelphia chromosome-positive disease, previous exposure to at least two TKIs and absence of a known T315I mutation.
• Review cardiac disease, QT-prolonging medicines, electrolytes, hypertension, previous pancreatitis and hepatic impairment.
• Test for hepatitis B before treatment; monitor carriers during treatment and for several months afterwards.
• Account for the clinically important reduction in exposure caused by food.

Contraindications and cautions

• Hypersensitivity to asciminib or any excipient.
• The lactose-containing tablets should not be used in rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Monitoring

• Complete blood count at baseline and regularly during treatment.
• Amylase and lipase, with more frequent assessment after previous pancreatitis or with suggestive abdominal pain.
• Blood pressure and clinical cardiovascular status.
• Baseline ECG and subsequent ECGs when clinically indicated; correct and monitor potassium and magnesium.
• Hepatitis B status and signs of reactivation.
• Clinical response, tolerability, hepatic tests and relevant interacting medicines.

Clinical pharmacology

Asciminib is an oral allosteric ABL/BCR::ABL1 inhibitor that binds the ABL myristoyl pocket. It is metabolised through CYP3A4, UGT2B7 and UGT2B17 pathways, is a BCRP and P-glycoprotein substrate and inhibitor, and is eliminated mainly in faeces.

Formulation and product differences

• The film-coated tablet strengths differ in size, colour, lactose content and iron-oxide colourants.
• Both tablet presentations are unscored and must be swallowed whole.

Tablet

Route: Oral

Strengths: 20 mg, 40 mg