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

Reversible posterior leukoencephalopathy syndrome in patients receiving ponatinib

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

RPLS is a neurologic disorder that can present with seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurologic 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 RPLS; two cases improved after treatment withdrawal, and did not reappear when restarted at a lower dose. RPLS is included in the warnings/precautions section of the US prescribing information.

Ponatinib (a tyrosine kinase inhibitor) is indicated for adults with chronic phase, accelerated phase, or blast phase chronic myelogenous leukemia 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



History and exam

Key diagnostic 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 hemorrhages

Risk factors

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

Diagnostic investigations

1st investigations to order

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

Treatment algorithm


Authors VIEW ALL

Honorary Consultant in Haematology

The Christie NHS Foundation Trust




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




RC declares that she has no competing interests.

Professor of Haematology

Royal Liverpool University Hospital




None disclosed.

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