Managing Adverse Events

Managing Nonhaematologic Adverse Events in Clinical Trials¹

Fluid retention and pleural effusion¹

• Fluid retention events were typically managed by supportive care measures that included diuretics and short courses of steroids
• Severe pleural effusion may require thoracentesis and/or oxygen medical treatment

Bleeding¹

Drug-related bleeding events were managed by:

• Drug interruption
• Transfusion

QT prolongation¹

Caution should be used in patients who may have or may develop prolongation of QT interval, including:

• Patients with hypokalemia
• Patients with hypomagnesemia
• Patients with congenital long QT syndrome
• Patients taking anti-arrhythmic medicines
• Patients taking other products leading to QT prolongation
• Patients on cumulative anthracycline medical treatment

Hypokalemia or hypomagnesemia should be corrected prior to SPRYCEL administration.
Approximately half to two thirds of the dasatinib-treated subjects who had normal baseline levels experienced transient hypocalcemia at some time during the course of the study. In general, there was no association of decreased calcium with clinical symptoms. Patients developing grade 3 or 4 hypocalcemia often had recovery with oral supplementation.¹

Other adverse events¹

The most frequently reported adverse reactions were fluid retention, diarrhoea, skin rash and headache, haemorrhage, fatigue, nausea, and dyspnoea.

Grade 3 or 4 elevations of transaminases or bilirubin were reported in ≤5% of patients with chronic or accelerated phase chronic myeloid leukaemia (CML), but elevations were reported with an increased frequency of 5% to 11% in patients with myeloid or lymphoid blast phase CML or Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). These were usually managed with dose reduction or interruption.

If a severe non-haematologic adverse reaction develops with SPRYCEL, treatment must be withheld until the event has resolved. Thereafter, treatment can be resumed as appropriate at a reduced dose, depending on the initial severity of the event.¹

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Managing Haematologic Adverse Events in Clinical Trials¹

• If a severe non-haematologic adverse reaction develops with SPRYCEL, treatment must be withheld until the event has resolved¹
• Thereafter, treatment can be resumed as appropriate at a reduced dose, depending on the initial severity of the event¹

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Dose adjustments: chronic phase CML patients resistant or intolerant to imatinib

Dose adjustments: Chronic Phase CML Patients

In patients who experienced severe myelosuppression, recovery generally occurred following brief dose interruptions and/or reductions, and permanent discontinuation of treatment occurred in 1% of patients.¹

• Myelosuppression was generally reversible and usually managed by withholding SPRYCEL temporarily or by dose reduction¹
  • Most patients continued treatment without further evidence of myelosuppression¹

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Dose adjustments: Advanced Phase CML or Ph+ ALL patients resistant or intolerant to prior therapy including imatinib

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Drug interactions

Certain drugs may increase or decrease exposure to SPRYCEL¹

CYP3A4 inhibitors may increase exposure to SPRYCEL and are not recommended for concomitant use.

CYP3A4 inducers may reduce exposure to SPRYCEL and potentially lead to therapeutic failure. Other agents with less potential for CYP3A4 induction should be selected.

For more information about drug interactions and special populations, please see the European Summary of Product Characteristics.

• H₂ blockers or protein pump inhibitors are not recommended¹
• Aluminium hydroxyde/magnesium hydroxyde products should be taken 2 hours before or 2 hours after SPRYCEL¹
• Caution should be exercised if patients are prescribed a medicinal product that inhibits platelet formation or anticoagulants¹

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