Voxelotor withdrawn globally due to safety concerns
Voxelotor, indicated for the treatment of sickle cell disease, has been voluntarily withdrawn from the worldwide market by the manufacturer due to serious safety concerns.[91] This includes discontinuing all ongoing clinical trials, as well as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]
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
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
Risk factors
- genetic
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
Tests to consider
- pulse oximetry
- plain x-rays of long bones
- bacterial cultures
- chest x-ray
Treatment algorithm
vaso-occlusive crisis
acute chest syndrome
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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