Sickle Cell Disease
Hydroxyurea for Sickle Cell Disease: Utilization and Adherence Patterns
In patients with sickle cell disease (SCD), hydroxyurea has been shown to reduce morbidity and mortality. Still, adherence to therapy may be a challenge, especially in adolescents and young adults. Open communication between patients and health care professionals can help identify barriers in an attempt to increase treatment adherence.
Associate Professor of Pediatrics
“It is helpful to remind patients that SCD has the potential to cause complications in nearly every organ over time, emphasizing the potential benefit of hydroxyurea on organ preservation and the importance of treatment adherence.”
In the past, hydroxyurea would only be offered to patients with SCD complications, but this has changed. The current recommendation is for all patients with SCD with the SS genotype to take hydroxyurea on a regular basis. And so, we, as pediatric hematologists, begin educating families about hydroxyurea during their first clinic visits and, typically, hydroxyurea is initiated by the age of 9 months. End-organ damage in SCD can begin early, in the spleen for instance, and we are seeing some preservation of splenic function with the earlier use of hydroxyurea.
In our discussions with parents about the side effects of hydroxyurea, we include the cytopenias, usually neutropenia or thrombocytopenia. Typically, we titrate to a maximum tolerated dose based on the patient’s absolute neutrophil count. Patient concerns about fertility and leukemia may also contribute to a reluctance to its use. While hydroxyurea does not render all patients infertile, we do think that it likely affects sperm counts, but how much impact hydroxyurea has on fertility in adulthood is an area that needs additional research. Leukemia development following hydroxyurea use has been a concern, but there have not been increased reports of leukemia in patients with SCD taking hydroxyurea as its use has become more widespread.
Adherence sometimes declines during adolescence and young adulthood, and it can be challenging to convince patients who are doing well to be adherent. Some may feel that they have too many medications to take, so they may be reluctant to start or continue hydroxyurea because they feel that it may simply be too much to manage. Others may have concerns about toxicities, but, in older adolescents and young adults, this can often be overcome with education. For patients who simply forget to take their medication, setting a reminder on their phones or keeping their medication next to their toothbrush may help improve treatment adherence. Blood count monitoring means a trip to the lab at least every 3 months, which might be a barrier for some individuals. In fact, for some, simply getting to the lab is a larger barrier than any particular concerns about the side effects of hydroxyurea.
When barriers to adherence stem from unfounded concerns, education is one of the best tools to overcome them. For instance, some patients have misconceptions associated with hydroxyurea owing to its use as a chemotherapeutic agent. Educating patients and families that hydroxyurea is not used as a single treatment but rather as part of a chemotherapy regimen may alleviate some of those fears. Additionally, it is helpful to remind patients that SCD has the potential to cause complications in nearly every organ over time, emphasizing the potential benefit of hydroxyurea on organ preservation and the importance of treatment adherence. It is also important to discuss that patients who are adherent to hydroxyurea treatment may still experience complications of SCD, such as vaso-occlusive crisis, but it typically lessens the frequency or severity of complications. Newer disease-modifying agents, such as voxelotor or crizanlizumab, might be used in combination with hydroxyurea in such cases.
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