Last reviewed: December 2018
Last updated: October  2018
30 Oct 2018

Posterior reversible encephalopathy syndrome in patients receiving ponatinib

Healthcare professionals are advised that there is a risk of posterior reversible encephalopathy syndrome (PRES, also known as reversible posterior leukoencephalopathy syndrome) in patients taking ponatinib. A routine European review suggests that the risk could be up to 1 in 100 people who are taking the medicine. Treatment should be interrupted if PRES is confirmed, and resumed only when it has resolved and if the benefits of continuing treatment outweigh the risk of PRES.

PRES is a neurological disorder that can present with seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances.

The advice comes from the UK Medicines and Healthcare products Regulatory Agency following a European post-marketing review of ponatinib that identified five cases of PRES; two cases improved after treatment withdrawal, and did not reappear when restarted at a lower dose. The UK Summary of Product Characteristics lists PRES as an uncommon undesirable effect (that could affect up to 1 in 100 people).

Ponatinib (a tyrosine kinase inhibitor) is indicated for adults with chronic phase, accelerated phase, or blast phase chronic myelogenous leukaemia who are resistant or unsuitable for treatment with other tyrosine kinase inhibitors, or who have the T315I mutation.

Patients receiving ponatinib should be advised to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • splenomegaly
  • shortness of breath
  • left upper quadrant discomfort or fullness
  • epistaxis
  • arthralgia
  • sternal tenderness

Other diagnostic factors

  • weight loss
  • excessive sweating
  • fever
  • pallor
  • bruising
  • retinal haemorrhages

Risk factors

  • age 65 to 74 years
  • ionising radiation exposure
  • male sex

Diagnostic investigations

1st investigations to order

  • FBC
  • complete metabolic profile
  • peripheral blood smear
  • bone marrow biopsy
  • cytogenetics
  • quantitative reverse transcription PCR (qRT-PCR) including breakpoint analysis
  • fluorescent in situ hybridisation (FISH)
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Honorary Consultant in Haematology

The Christie NHS Foundation Trust

Manchester

UK

Disclosures

TS has received travel support and speaker expenses from Novartis, and has served as a consultant to Novartis for development of drugs for indications other than CML.

Dr Tim Somervaille would like to gratefully acknowledge Dr Han Myint and Dr Robert Chen, the previous contributors to this monograph. HM sits on the advisory board of Novartis and Bristol-Myers Squibb, and also does speaking engagements on their behalf. RC declares that he has no competing interests.

Peer reviewers VIEW ALL

Chief Fellow

Section of Hematology and Oncology

Department of Internal Medicine

Wake Forest University Baptist Medical Center

Winston-Salem

NC

Disclosures

RC declares that she has no competing interests.

Professor of Haematology

Royal Liverpool University Hospital

Liverpool

UK

Disclosures

None disclosed.

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