Scemblix Special Precautions

Myelosuppression: Thrombocytopenia, neutropenia and anaemia have occurred in patients receiving Scemblix. Severe (NCI CTCAE grade 3 or 4) thrombocytopenia and neutropenia have been reported during treatment with Scemblix (see Adverse Reactions). Myelosuppression was generally reversible and was managed by temporarily withholding Scemblix.
A complete blood count should be performed every 2 weeks in the first 3 months of treatment and then monthly thereafter or as clinically indicated. Patients should be monitored for signs and symptoms of myelosuppression.
Based on the severity of thrombocytopenia and/or neutropenia, the Scemblix dose should be reduced, temporarily withheld or permanently discontinued as described in Table 4 (see Dosage & Administration).
Pancreatic toxicity: Pancreatitis occurred in 11 of 556 (2%) patients receiving Scemblix, with grade 3 adverse drug reactions occurring in 6 (1.1%) patients. Scemblix was permanently discontinued in 3 (0.5%) patients, while it was temporarily withheld in 5 (1.1%) patients due to pancreatitis. Asymptomatic elevations of serum lipase and amylase occurred in 107 of 556 (19.2%) patients receiving Scemblix treatment, with grade 3 and 4 adverse drug reactions occurring in 41 (7.4%) and 11 (2%) patients, respectively. Scemblix was permanently discontinued in 11 (2%) patients due to asymptomatic elevation of serum lipase and amylase.
Serum lipase and amylase levels should be assessed monthly during treatment with Scemblix 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. If serum lipase and amylase elevation is accompanied by abdominal symptoms, treatment should be temporarily withheld and appropriate diagnostic tests should be considered to exclude pancreatitis (see Dosage & Administration).
Based on the severity of the serum lipase and amylase elevation, the Scemblix dose should be reduced, temporarily withheld or permanently discontinued as described in Table 4 (see Dosage & Administration).
QT prolongation: Electrocardiogram QT prolongation occurred in 5 of 556 (0.9%) patients receiving Scemblix treatment (see Adverse Reactions). In the ASCEMBL clinical study one patient had a prolonged QTcF greater than 500 ms together with a more than 60 ms QTcF increase from baseline and one patient had a prolonged QTcF with a more than 60 ms QTcF increase from baseline.
It is recommended that an electrocardiogram is performed prior to the start of treatment with Scemblix and that ECG monitoring is carried out during treatment as clinically indicated. Hypokalaemia and hypomagnesaemia should be corrected prior to Scemblix administration and monitored during treatment as clinically indicated.
Caution is required when co-administering Scemblix at a total daily dose of 80 mg with medicinal products with a known risk of torsades de pointes. Co-administration of Scemblix 200 mg twice daily with medicinal products with a known risk of torsades de pointes should be avoided (see Interactions and Pharmacology: Pharmacokinetics under Actions).
Hypertension: Hypertension occurred in 88 of 556 (15.8%) patients receiving Scemblix treatment, with grade 3 and 4 adverse drug reactions reported in 47 (8.5%) and 1 (0.2%) patients, respectively. Among the patients with ≥ grade 3 hypertension, the median time to first occurrence of adverse drug reactions was 21.29 weeks (range: 0.14 to 365 weeks). Scemblix was temporarily withheld in 5 (0.9%) patients due to hypertension.
Hypertension should be monitored and managed with standard antihypertensive therapy during treatment with Scemblix as clinically indicated.
Hypersensitivity: Hypersensitivity events occurred in 169 of 556 (30.4%) patients receiving Scemblix, with ≥ grade 3 events reported in 8 (1.4%) patients. Patients should be monitored for signs and symptoms of hypersensitivity and appropriate treatment should be initiated as clinically indicated.
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). Patients should be tested for HBV infection before the start of treatment with Scemblix. HBV carriers who require treatment with Scemblix should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy.
Embryo-foetal toxicity: Based on findings from animal studies, Scemblix can cause foetal harm when administered to a pregnant woman. Pregnant women and women of child-bearing potential should be advised of the potential risk to the foetus if Scemblix is used during pregnancy or if the patient becomes pregnant while taking Scemblix. The pregnancy status of women of child-bearing potential should be verified prior to starting treatment with Scemblix. Sexually active women of childbearing potential should use effective contraception during treatment with Scemblix and for at least 3 days after the last dose (see Use in Pregnancy & Lactation).
Other components: The tablets contain lactose. Patients with the rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product contains less than 1 mmol (23 mg) of sodium per tablet, making it practically "sodium-free".
Patients excluded from clinical studies: Patients with severe or uncontrolled medical conditions, including any bleeding disorders, with a history of or risk factors for pancreatitis, or with clinically significant cardiac impairment or cardiac repolarisation abnormalities were not included in clinical studies for asciminib.
Effects on ability to drive and use machines: No relevant studies have been performed. Patients experiencing dizziness, fatigue, nausea, visual impairment or other adverse effects with a potential impact on the ability to drive or use machines should refrain from these activities as long as the adverse effects persist (see Adverse Reactions).