Upon the meeting of its Pharmacovigilance Risk Assessment Committee (PRAC) held from 7 to 10 June 2022, the European Medicines Agency (EMA) issued Direct Healthcare Professional Communications (DHPC) to inform healthcare professionals of the risk of ocular toxicity, severe visual loss and the need for monitoring in paediatric patients treated with crizotinib (Xalkori).

Crizotinib is a cancer medicine used to treat adults with advanced ALK-positive non-small cell lung cancer. It has been studied in children from 6 to 18 years of age as a monotherapy for the treatment of relapsed or refractory systemic anaplastic large cell lymphoma that is ALK-positive or patients with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumour.

Vision disorders have been reported in 61% of paediatric patients treated with crizotinib in clinical trials for these indications.

Vision disorders and ocular toxicity are more challenging to detect in children. Young patients may not report or notice changes in vision without specific questioning of symptoms and examinations. Paediatric patients should be monitored for ocular toxicity, including the risk of severe vision loss. They should receive a baseline ophthalmologic examination prior to starting crizotinib with follow-up examinations. Healthcare professionals are advised to inform patients and caregivers of the symptoms and remind them to contact their doctor if any of these symptoms develop. Any visual symptoms should be referred to an eye specialist.

Healthcare professionals are also advised to consider a dose reduction of crizotinib for patients who develop Grade 2 ocular disorders. If Grade 3 and 4 ocular disorders occur, treatment with the medicine should be discontinued permanently, unless another cause is identified.

The product information and the educational material for patients and caregivers have been updated with instructions/recommendations in children about the risk of ocular toxicity, including severe vision loss.

The DHPC for Xalkori will be forwarded to EMA’s Committee for Medicinal Products for Human use (CHMP). Following the CHMP decision, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registries in EU Member States.