Chinese instruction manual for Glasdegib

1. Name:Glasdegib

Product name: Daurismo

Other names: Glasgibb, Glasgibb (transliteration)

2. Indications:

Glasdegib is indicated for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults ≥75 years of age or with comorbidities that preclude the use of intensive induction chemotherapy in combination with low-dose cytarabine.

3. Usage and dosage:

1. Recommended dosage and regimen

In the absence of unacceptable toxicity or loss of disease control, the recommended dose of glasgibe is cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle and 100 mg orally once daily on days 1 to 28. For patients without unacceptable toxicity, treat for at least 6 cycles to allow time for clinical response.

Glasgib can be taken with or without food. Do not split or crush Glasgibb tablets. Take it at about the same time every day. If vomiting occurs after taking this dose, do not use an alternative dose; wait until the next scheduled dose is due. If a dose is missed or not taken at the usual time, take the dose as soon as possible and at least 12 hours before the next scheduled dose. Back to normal schedule the next day. Do not take 2 doses of Glasgib within 12 hours.

2. Monitoring and dose adjustment

Assess complete blood count, electrolytes, renal function, and liver function before starting GLAZIB, at least weekly for the first month. Monitor electrolytes and kidney function monthly during treatment. Monitor to assess for QTc prolongation before initiating glasgibe and as clinically indicated thereafter (e.g., if muscle symptoms are reported, obtain creatine phosphokinase [CPK] levels; monitor electrocardiogram [ECG] before initiating treatment, approximately one week after initiation), and then monthly for the next two months. If abnormal, repeat the ECG. Some patients may require more frequent and continuous ECG monitoring. Handle any abnormal situations promptly.

3. Dose adjustment when combined with moderate CYP3A4 inducers

Avoid concomitant use of glazegib with moderate CYP3A4 inducers. If combined use cannot be avoided, adjust the dosage, for example, adjust the dosage from 100 mg orally once a day to 200 mg orally once a day; adjust the dosage from 50 mg orally once a day to 100 mg orally once a day. Seven days after discontinuation of the moderate CYP3A4 inducer, resume the dose of Glasgib taken before starting the moderate CYP3A4 inducer.

4. Adverse reactions:

In clinical studies at Glasgibb, the most common adverse reactions were anemia, fatigue, bleeding, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.

5. Supply and storage:

Glasgib is available as100 mg and 200 mg tablets and in bottles of 30 and 60 tablets. It can be stored at 20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C (59°F to 86°F).

6. Mechanism of action:

Glasgib is an inhibitor of the Hedgehog pathway. Glasgib binds and inhibits Smoothened, a transmembrane protein involved in hedgehog signaling. In a murine xenograft model of human AML, glazegib combined with low-dose cytarabine inhibited the increase in tumor size and reduced the percentage of CD45+/CD33+ blasts in the bone marrow to a greater extent than glazegib or low-dose cytarabine alone.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=204a6f7e-c9a4-472b-abd2-9527bda64d17##