Scemblix

Treatment should be initiated by a physician experienced in the diagnosis and treatment of patients with leukaemia. Posology Ph+ CML-CP The recommended total daily dose of asciminib is 80 mg. 4). Patients switching from 40 mg twice daily to 80 mg once daily should start taking asciminib once daily approximately 12 hours after the last twice-daily dose, and then continue at 80 mg once daily.

Patients switching from 80 mg once daily to 40 mg twice daily should start taking asciminib twice daily approximately 24 hours after the last once-daily dose, and then continue at 40 mg twice daily at approximately 12-hour intervals.

The decision on the appropriate dosage regimen should be taken at the prescriber’s discretion as necessary for the benefit of the patient. Ph+ CML-CP with the T315I mutation in patients resistant to, intolerant to or ineligible for ponatinib The recommended dose is 200 mg twice daily at approximately 12-hour intervals.

Use of the 100 mg film-coated tablets is restricted to patients with Ph+ CML-CP with the T315I mutation.

Missed dose Once-daily dosage regimen:

If a dose is missed by less than 12 hours, it should be taken and the next dose should be taken as scheduled. If a dose is missed by more than approximately 12 hours, it should be skipped and the next dose should be taken as scheduled.

4 Twice-daily dosage regimen: If a dose is missed by less than 6 hours, it should be taken and the next dose should be taken as scheduled. If a dose is missed by more than approximately 6 hours, it should be skipped and the next dose should be taken as scheduled.

Treatment duration Treatment with asciminib should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs. Dose adjustments for adverse reactions Ph+ CML-CP The starting dose is 80 mg once daily or 40 mg twice daily, while the reduced dose is 40 mg once daily or 20 mg twice daily, respectively.

The dose can be modified based on individual safety and tolerability as shown in Table 1. Asciminib should be permanently discontinued in patients unable to tolerate a dose of 40 mg once daily or 20 mg twice daily. Ph+ CML-CP with the T315I mutation in patients resistant to, intolerant to or ineligible for ponatinib The starting dose is 200 mg twice daily, while the reduced dose is 160 mg twice daily.

7%). 2%). 9% of patients receiving asciminib. 1%). Ph+ CML-CP with the T315I mutation in patients resistant to, intolerant to or ineligible for ponatinib (X2101 study) The safety dataset for the 200 mg twice-daily dose is limited to 48 patients, of whom 34 had a treatment intensity of >90%.

8%). 3%). 5% of patients receiving asciminib. 1%). Tabulated list of adverse reactions The overall safety profile of asciminib has been evaluated in 556 patients with Ph+ CML in chronic (CP) and accelerated (AP) phases in the pivotal phase III study A2301 (ASCEMBL) and the phase I study X2101, and with newly diagnosed Ph+ CML-CP in the pivotal phase III study J12301 (ASC4FIRST).

In ASCEMBL (N=156), patients received asciminib as monotherapy at a dose of 40 mg twice daily. In X2101 (N=200), patients received asciminib as monotherapy at doses ranging from 10 to 200 mg twice daily and 80 to 200 mg once daily. Of these patients, 48 with the T315I mutation received asciminib 200 mg twice daily.

In ASC4FIRST (N=200), patients received asciminib as monotherapy at a dose of 80 mg once daily. 1 to 439 weeks). Adverse reactions from clinical studies (Table 2) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000).

11 Table 2 Adverse reactions observed with asciminib in clinical studies System organ class Frequency category Adverse reaction Infections and infestations Very common Upper respiratory tract infection1 Common Lower respiratory tract infection2, influenza Blood and lymphatic system disorders Very common Thrombocytopenia3, neutropenia4, anaemia5 Uncommon Febrile neutropenia, pancytopenia Immune system disorders Uncommon Hypersensitivity Endocrine disorders Common Hypothyroidism6 Metabolism and nutrition disorders Very common Dyslipidaemia7 Common Decreased appetite, hyperglycaemia Nervous system disorders Very common Headache, dizziness Eye disorders Common Dry eye, vision blurred Cardiac disorders Common Palpitations Vascular disorders Very common Hypertension8 Respiratory, thoracic and mediastinal disorders Very common Cough Common Pleural effusion, dyspnoea, non-cardiac chest pain Gastrointestinal disorders Very common Pancreatic enzymes increased9, vomiting, diarrhoea, nausea, abdominal pain10, constipation Common Pancreatitis11 Hepatobiliary disorders Very common Hepatic enzyme increased12 Common Blood bilirubin increased13 Skin and subcutaneous tissue disorders Very common Rash14, pruritus Common Urticaria Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain15, arthralgia General disorders and administration site conditions Very common Fatigue16 Common Oedema17, pyrexia18 Investigations Common Blood creatine phosphokinase increased Uncommon Electrocardiogram QT prolonged 1 Upper respiratory tract infection includes: upper respiratory tract infection, nasopharyngitis, pharyngitis and rhinitis.

Ph+ CML-CP with the T315I mutation in patients resistant to, intolerant to or ineligible for ponatinib In patients with Ph+ CML-CP with the T315I mutation treated with the 200 mg twice-daily dose, close monitoring should be considered since there are uncertainties regarding a potential increase of safety risks compared to the 80 mg total daily dose due to the small dataset of 48 patients, of whom 34 had a treatment intensity of >90%.

Myelosuppression Thrombocytopenia, neutropenia and anaemia occurred in patients receiving asciminib. 8). Myelosuppression was generally reversible and managed by temporarily withholding treatment. Complete blood counts should be performed every two weeks for the first 3 months of treatment and then monthly thereafter, or as clinically indicated.

Patients should be monitored for signs and symptoms of myelosuppression. 2). 8). Serum lipase and amylase levels should be assessed monthly during treatment with asciminib, or as clinically indicated. Patients should be monitored for signs and symptoms of pancreatic toxicity.

More frequent monitoring should be performed in patients with a history of pancreatitis. 2). 2). 8). It is recommended that an electrocardiogram is performed prior to the start of treatment with asciminib, and monitored during treatment as clinically indicated.

Hypokalaemia and hypomagnesaemia should be corrected prior to asciminib administration and monitored during treatment as clinically indicated. Caution should be exercised when administering asciminib at a total daily dose of 80 mg concomitantly with medicinal products with known risk of torsades de pointes.

1). 8). Hypertension and other cardiovascular risk factors should be monitored regularly and managed using the standard therapies during treatment with asciminib. 7 Hepatitis B reactivation Reactivation of hepatitis B virus (HBV) has occurred in patients who are chronic carriers of this virus following administration of other BCR::ABL1 tyrosine kinase inhibitors (TKIs).

1.