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Sickle cell anemia

Last reviewed: 6 Oct 2024
Last updated: 27 Sep 2024
01 Oct 2024

Voxelotor withdrawn globally due to safety concerns

Voxelotor, indicated for the treatment of sickle cell disease, has been voluntarily withdrawn from the worldwide market by the manufacturer due to serious safety concerns.[91]​ This includes discontinuing all ongoing clinical trials, as well as compassionate use and expanded access programs.

Healthcare professionals are advised to:

  • stop prescribing voxelotor for new patients with sickle cell disease

  • contact patients already taking voxelotor to advise on stopping treatment and discuss alternative options; patients must talk to their doctor before stopping voxelotor

  • monitor patients for adverse events after treatment with voxelotor is stopped, and ensure patients are followed-up appropriately

  • report adverse events to the relevant regulatory body.

The decision to withdraw voxelotor is based on clinical data that indicates the overall benefit of voxelotor no longer outweighs the risk in patients with sickle cell disease.

Higher rates of vaso-occlusive crises and deaths have been reported in patients taking voxelotor compared with placebo in clinical trials. Real-world registry studies also recorded higher rates of vaso-occlusive crisis in patients with sickle cell disease taking voxelotor.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently conducting safety reviews of all the available data.[74][75]

See Management: approach

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • parent(s) diagnosed with sickle cell anemia, other sickle cell disease, or sickle cell trait
  • persistent pain in skeleton, chest, and/or abdomen
  • dactylitis
Full details

Other diagnostic factors

  • high temperature
  • pneumonia-like syndrome
  • bone pain
  • visual floaters
  • tachypnea
  • failure to thrive
  • pallor
  • jaundice
  • tachycardia
  • lethargy
  • protuberant abdomen, often with umbilical hernia
  • cardiac systolic flow murmur
  • maxillary hypertrophy with overbite
  • shock
Full details

Risk factors

  • genetic
Full details

Diagnostic tests

1st tests to order

  • DNA-based assays
  • hemoglobin isoelectric focusing (Hb IEF)
  • cellulose acetate electrophoresis
  • high-performance liquid chromatography (HPLC) fractionation
  • hemoglobin solubility testing
  • peripheral blood smear
  • CBC and reticulocyte count
  • iron studies
Full details

Tests to consider

  • pulse oximetry
  • plain x-rays of long bones
  • bacterial cultures
  • chest x-ray
Full details

Treatment algorithm

ACUTE

vaso-occlusive crisis

acute chest syndrome

ONGOING

chronic disease

Contributors

Authors

Sophie Lanzkron, MD, MHS

Director

Sickle Cell Center for Adults

Associate Professor of Medicine and Oncology

Johns Hopkins Medicine

Baltimore

MD

Disclosures

SL declares consultancy (Bluebird bio, Novo Nordisk, Pfizer, Novartis, Magenta); honoraria (Novartis); research funding (Imara, Novartis, GBT, Takeda, CSL-Behring, HRSA, PCORI, MD CHRC); stocks (Pfizer, Teva). SL is on the executive board of the National Alliance for Sickle Cell Centers (uncompensated).

Acknowledgements

Dr Sophie Lanzkron would like to gratefully acknowledge Dr Channing Paller, a previous contributor to this topic.

Disclosures

CP declares that she has no competing interests.

Peer reviewers

James Bradner, MD

Instructor in Medicine

Division of Hematologic Neoplasia

Dana-Farber Cancer Institute

Boston

MA

Disclosures

JB declares that he has no competing interests.

Adrian Stephens, MB BS, MD, FRCPath

Consultant Haematologist

University College London Hospitals

London

UK

Disclosures

AS declares that he has no competing interests.

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