Monitoring requirements for crizotinib have been revised following a review conducted by the MHRA and other EU regulators. Healthcare professionals should be vigilant for signs and symptoms of cardiac failure, including dyspnoea, oedema and rapid weight gain from fluid retention. If such symptoms occur, appropriate measures such as dosing interruption, dose reduction or treatment discontinuation should be considered.
Forty cases of cardiac failure were reported during post-marketing surveillance of crizotinib to February 25, 2015. In most cases cardiac failure occurred within the first month of starting therapy. A fatal outcome was reported for 15 of these cases.
In seven cases, symptoms of cardiac failure resolved after discontinuation of crizotinib, three of which saw patients experience a recurrence of symptoms when crizotinib was re-introduced. Of the seven cases, three showed no pre-existing cardiac disorders, comorbid conditions or concurrent medications.
Cardiac failure is now listed as a common adverse effect in the Xalkori Summary of Product Characteristics.