Hydroxyurea in Pediatric Patients with Sickle Cell Anemia

Testing a formulation of hydroxyurea in children; this drug is approved to treat sickle cell disease in adults.

This study examined the pharmacokinetics of liquid hydroxyurea in approximately 16 children aged 2 to <5 years and the relative bioavailability in approximately 24 children aged >5 to 17 years. Children enrolled had a diagnosis of sickle cell anemia or sickle beta-zero thalassemia. The study period lasted a minimum of 30 days from the first dose.

Kathleen Neville, MD, of Children's Mercy Hospital Kansas City, discusses the PTN study of hydroxyurea in pediatric patients with sickle cell anemia.


Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal crescent shape (as opposed to the normal disc shape). These fragile, sickle-shaped cells deliver less oxygen to the body's tissues. They can also clog more easily in small blood vessels and break into pieces that disrupt healthy blood flow. Common symptoms of sickle cell anemia include attacks of abdominal pain, bone pain, delayed growth and puberty, fatigue, fever, and ulcers on the lower legs.

Hydroxyurea (HU) represents the only major medical breakthrough in sickle cell disease in the past 20 years, and it is the only drug that is approved by the U.S. Food and Drug Administration (FDA) for treatment in adults with sickle cell disease. Treatment with HU has been shown to significantly decrease the incidence of painful episodes and also reduces overall mortality in adult patients. In spite of the fact that the FDA has not approved HU for pediatric use, it is often used to treat children who exhibit signs of severe disease. Recent data suggest that use of HU in infants with sickle cell disease is feasible, well-tolerated, and efficacious; however, only limited pharmacokinetic and pharmacodynamic studies have been done on HU use in children.

This study was designed to better understand how this drug works in children. Approximately 40 children with sickle cell disease were enrolled and given a liquid formulation of HU. Sixteen participants aged 2 to <5 years were enrolled in the pharmacokinetic study, and up to 24 participants aged >5 to 17 years were enrolled in the relative bioavailability study (in which the liquid formulation was compared with Droxia®). Blood samples were obtained after HU administration to determine study drug concentrations in the body and its elimination. The study period was a minimum of 30 days from the first dose of HU.


The study found that liquid and capsule formulations of HU are bioequivalent and that weight-based dosing schemes provide consistent drug exposure. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature, these findings should encourage the use of HU across the spectrum of age and weight in children with sickle-cell anemia.




Completed; clinical study report submitted to FDA

ClinicalTrials.gov identifier:

Principal Investigators:
Kathleen Neville, MD, MS
Mercy Children's Hospital
Kansas City, MO

Zora R. Rogers, MD
University of Texas Southwestern
Dallas, TX


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