Advice for healthcare professionals:
post-marketing cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving ponatinib; the risk could be up to 1 in 100 people taking the medicine
presenting signs and symptoms of PRES include seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances
interrupt treatment if PRES is confirmed and resume treatment only once the event is resolved and if the benefit of continued treatment outweighs the risk of PRES
advise patients to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes
black triangle medicines are intensively monitored to ensure that any new safety hazards are identified promptly – report any suspected adverse drug reactions on a Yellow Card
Reports of posterior reversible encephalopathy syndrome
A routine EU review assessed cases of posterior reversible encephalopathy syndrome reported in patients receiving ponatinib. In a cumulative review, 5 cases of PRES were identified, 2 of which were confirmed with MRI. Two cases showed a positive de-challenge effect (symptoms improved after ponatinib withdrawal). In both cases, signs and symptoms of PRES did not reappear when ponatinib was restarted at a lower dose (negative re-challenge at reduced dose).
Risk of PRES has been added to the list of adverse events associated with ponatinib in the Summary of Product Characteristics and Patient Information Leaflet with a frequency of uncommon (could affect up to 1 in 100 people taking the medicine).
No UK Yellow Card reports have been received for PRES association with ponatinib treatment, but use in the UK is low and continued vigilance is recommended.
About posterior reversible encephalopathy syndrome (PRES)
PRES is a neurological disorder that can present with signs and symptoms such as seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances. Characteristic radiographic findings include bilateral regions of subcortical vasogenic oedema that resolve within days or weeks.
Hypertension including hypertensive crisis is an established reaction associated with ponatinib treatment and may contribute to the risk of PRES.
About ponatinib (Iclusig▼)
Iclusig is indicated for adult patients with:
Chronic-phase, accelerated-phase, or blast-phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation
Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
Prescribers are reminded of previous advice on dose reduction in relation to the risk of serious vascular occlusive events with this medicine (see Drug Safety Update, April 2017).
Report any suspected adverse drug reactions
Please continue to report any suspected adverse reactions to Ponatinib via the Yellow Card Scheme. Your report will help us safeguard public health.
Article citation: Drug Safety Update volume 12, issue 3: October 2018: 3.
Published 11 October 2018