Xalkori: Ocular Toxicity and Severe Visual Loss in Children

Last Updated on June 26, 2022 by Joseph Gut – thasso

25 June 2022 – Xalkori (Crizotinib)-related ocular toxicity and severe visual loss are difficult to detect in children. This comes out of a Dear Healthcare Professional Communication (DHPC) letter from the European Medicine Agency (EMA) following it’s June 2022 Pharmacovigilance Risk Assessment Committee (PRAC) Meeting which informs healthcare professionals of the risk of ocular toxicity, severe visual loss and the need for monitoring in paediatric patients with Xalkori (Crizotinib.

Xalkori (Crizotinib) is a cancer medicine used to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC), when the disease is advanced. Xalkori (Crizotinib) 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 (ALCL) that is ALK positive or patients with unresectable, recurrent, or refractory ALK positive inflammatory myofibroblastic tumour (IMT). Vision disorders have been reported in 61% of paediatric patients treated with Xalkori (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 Xalkori (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 Xalkori (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 DHPCs for Xalkori (Crizotinib) will be forwarded to EMA’s human medicines committee, the CHMP. Following the CHMP decision, the DHPCs 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 registers in EU Member States.

This case illustrates the necessity to carefully investigate clinically the effects of medicines, including the so called targeted medicines, in all subgroups of patients, particularly in age groups.This may particularly become important with the so called tumor-agnostic drugs which now increasingly are approved based mainly on the observation that the cancer cells have specific gene or protein changes, regardless of where the cancer started in the body. Unfortunately, to date, other drug regulatory authorities such as the American Food and Drug Administration (FDA) and others have not yet reacted to the above findings in in the particular indications in pediatric patients. We are waiting.

Apart from the present discussion on Xalkori (Crizotinib), thasso has already had in the past posts related to Xalkori (Crizotinib) here, here, and here.