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Daurismo is a brand name for Glasdegib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Daurismo is indicated, in combination with low-dose cytarabine, for the treatment of newly diagnosed de novo or secondary acute myeloid leukaemia (AML) in adult patients who are not candidates for standard induction chemotherapy.
Verbatim from this product's EMA label. Tap a section to expand.
Daurismo should only be prescribed by or under the supervision of a physician experienced in the use of anticancer medicinal products. 1). Glasdegib should be continued as long as the patient is deriving clinical benefit. Delayed or missed doses of glasdegib If a dose is vomited, a replacement dose should not be administered; patients should wait until the next scheduled dose is due.
If a dose is missed or not taken at the usual time, then it should be taken as soon as the patient remembers unless more than 10 hours have passed since the scheduled dosing time, in which case the patient should not take the missed dose.
Patients should not take 2 doses at the same time to make up for a missed dose. Dose modifications Dose modifications may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose of glasdegib should be reduced to 50 mg taken orally once daily.
Dose modification and management guidelines for specific adverse reactions are provided in Tables 1, 2, 3 and 4. 2). 4). 4). 4). Table 1. Dose modification and management for adverse reactions – QT interval prolongation (corrected QT interval prolongation on at least 2 separate electrocardiograms (ECGs)) Adverse reaction: ECG QT Prolonged Dose modification and management recommendations Corrected QT interval 480 msec to 500 msec Assess electrolyte levels and supplement as clinically indicated.
5). Monitor ECGs at least weekly for 2 weeks following resolution of QT prolongation to less than or equal to 480 msec. Corrected QT interval greater than 500 msec Assess electrolyte levels and supplement as clinically indicated. 5). Interrupt Daurismo.
Resume Daurismo at a reduced dose of 50 mg once daily when corrected QT interval returns to within 30 msec of baseline or less than or equal to 480 msec. 4 Monitor ECGs at least weekly for 2 weeks following resolution of QT prolongation.
Consider re-escalating the dose of Daurismo to 100 mg daily if an alternative aetiology for the QT prolongation can be identified. Corrected QT interval prolongation and life-threatening arrhythmia Discontinue Daurismo permanently. Table 2.
5 x ULN] Continue Daurismo at the same dose and monitor CK levels weekly until resolution to baseline and then monthly. Monitor muscle symptoms for changes until resolution to baseline. Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated.
Summary of the safety profile The overall safety profile of Daurismo is based on data from clinical studies, including Study 1 in 84 patients with AML (N=75) and high-risk MDS (N=9). 5 days. 2%). 3%). 3%). Tabulated list of adverse reactions Table 6 presents adverse reactions reported with Daurismo.
The adverse reactions are listed by system organ class and frequency category. Frequency categories are defined as: very common (≥ 1/10) and common (≥ 1/100 to < 1/10). Within each frequency grouping, adverse reactions are presented in decreasing order of all grade frequencies.
6 13 13 a. Dysgeusia includes the following preferred terms: dysgeusia, ageusia. b. Electrocardiogram QT prolonged includes the following preferred terms: electrocardiogram QT prolonged, ventricular tachycardia. c. Haemorrhages includes the following preferred terms: petechiae, epistaxis, contusion, haematoma, haemorrhage intracranial, purpura, rectal haemorrhage, anal haemorrhage, ecchymosis, gastrointestinal haemorrhage, gingival bleeding, haematuria, haemorrhage, mouth haemorrhage, cerebral haemorrhage, conjunctival haemorrhage, eye contusion, eye haemorrhage, gastric haemorrhage, haematemesis, haemoptysis, haemorrhoidal haemorrhage, implant site haematoma, injection site bruising, retroperitoneal haematoma, subarachnoid haemorrhage, thrombotic thrombocytopenic purpura, tracheal haemorrhage, urethral haemorrhage.
d. Abdominal pain includes the following preferred terms: abdominal pain, abdominal pain upper, abdominal pain lower. 12 e. Rash includes the following preferred terms: erythema, pruritus, rash, rash macular, rash maculo-papular, rash pruritic.
f. Muscle spasms includes the following preferred terms: muscle contractions involuntary, muscle spasms, muscle tightness, musculoskeletal pain, myalgia. 8% in the low-dose cytarabine alone arm. 7% of patients in the Daurismo with low-dose cytarabine arm compared to none in the low-dose cytarabine alone arm.
Embryo-foetal toxicity Based on its mechanism of action and findings from animal embryo-foetal developmental toxicity studies, Daurismo can cause embryo-foetal death or severe birth defects when administered to a pregnant woman. 6).
Daurismo should not be used during pregnancy and in women of childbearing potential not using contraception. The pregnancy status of female patients of childbearing potential should be verified prior to initiating treatment with Daurismo.
6). Males Glasdegib may be present in semen. 6). 6). Based on non-clinical safety findings, glasdegib has the potential to impair reproductive function in males. 6). 4% of the patients treated with low-dose cytarabine alone. Electrolytes should be assessed prior to initiation of Daurismo, at least once weekly for the first month, and then once monthly for the duration of therapy.
Electrolyte abnormalities should be corrected. Concomitant medicinal products should be assessed. For medicinal products that have known QT prolonging effects and/or strong CYP3A4 inhibitor potential, alternatives should be considered.
ECGs should be monitored prior to the initiation of Daurismo, approximately one week after initiation, and then once monthly for the next two months to assess for QTc prolongation. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medicinal products with known QT prolonging effects, more frequent ECG monitoring is recommended.
ECG should be repeated if abnormal. 5). Blood cell counts and hepatic function monitoring Complete blood counts and hepatic function should be assessed prior to the initiation of therapy and at least once weekly for the first month. Thereafter, hepatic function and blood cell counts should be monitored as clinically indicated but at least monthly.
2). 8% of the patients treated with low-dose cytarabine alone. All patients starting therapy with Daurismo must be informed of the risk of muscle-related adverse events. They must be instructed to report promptly any unexplained muscle pain, tenderness or weakness occurring during treatment with Daurismo or if symptoms persist after discontinuing treatment.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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5 x ULN - 5 x ULN] Interrupt Daurismo and monitor CK levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. Upon resolution, resume Daurismo at the same dose level and measure CK monthly thereafter.
Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. If symptoms re-occur, interrupt Daurismo until resolution to baseline. Re-introduce Daurismo at 50 mg daily and follow the same monitoring recommendations.
If symptoms persist, consider discontinuing Daurismo. Grade 3 or 4 without renal impairment (serum Cr ≤ ULN) [Grade 3 (CK elevation > 5 x ULN - 10 x ULN)] [Grade 4 (CK elevation > 10 x ULN)] Interrupt Daurismo and monitor CK levels weekly until resolution to baseline.
Monitor muscle symptoms for changes until resolution to baseline. Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. If renal function is not impaired and CK resolves to baseline, consider resuming Daurismo at 50 mg daily.
CK levels should be measured weekly for 2 months after re-administration of Daurismo and monthly thereafter. 0) If renal function is impaired, interrupt Daurismo and ensure that the patient is adequately hydrated and evaluate other secondary causes of renal impairment.
Monitor CK and serum creatinine levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. 5 If CK and serum creatinine levels return to baseline, consider resuming Daurismo at 50 mg daily and measure CK levels weekly for 2 months and monthly thereafter; otherwise discontinue treatment permanently.
Abbreviations:
CK=creatine kinase; Cr=creatinine; ULN=upper limit of normal; CTCAE=Common Terminology Criteria for Adverse Events. Table 3. Dose modification and management for adverse reactions – Haematologic toxicity Adverse reaction: Haematologic toxicity Dose modification and management recommendations Platelets less than 10 x 109/L for more than 42 days in the absence of disease Discontinue Daurismo and low-dose cytarabine […]
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
g. if muscle signs and symptoms are reported). Management of high-grade CK elevation based on current standards of medical practice and following appropriate treatment guidelines is recommended. 2). Renal impairment Patients with pre-existing renal impairment or risk factors for renal dysfunction should be monitored closely.
Renal function should be assessed prior to initiation of therapy and at least once weekly for 8 the first month of therapy with Daurismo. 2). Excipients Lactose intolerance Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium-free”.