Changing the Course of SCD: One Dose of Hydroxyurea at a Time

Sickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the β-globin gene, leading to the production of sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes and causes red blood cells to take on a sickled shape. This leads to vaso-occlusion, chronic hemolytic anemia, and organ damage. Patients experience recurrent pain crises, infections, and shortened life expectancy.

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Benefits of Hydroxyurea

Hydroxyurea was the first FDA-approved disease-modifying therapy for SCD and remains the most accessible option today. Its mechanism involves inhibition of ribonucleotide reductase, which increases fetal hemoglobin (HbF) production, reduces HbS polymerization, and decreases red cell adhesion and inflammation. The result is fewer vaso-occlusive crises (VOCs), reduced hospitalizations, and improved survival.

A clinical consultation review published in the American Journal of Health-System Pharmacy emphasizes the pharmacist’s role in optimizing hydroxyurea therapy.

Pharmacist-led interventions have been shown to improve adherence, guide dose escalation to the maximum tolerated dose (MTD), and manage adverse effects, leading to better patient outcomes.

The landmark Multicenter Study of Hydroxyurea (MSH) demonstrated that hydroxyurea significantly reduced VOC frequency, acute chest syndrome, and transfusion needs in adults with SCD.

Pediatric studies such as HUG-KIDS and BABY HUG confirmed hydroxyurea’s safety and efficacy in children as young as 9 months. Hydroxyurea has not been linked to impaired growth in children or significant long-term safety concerns.

Hydroxyurea is typically started at 15-20 mg/kg/day and titrated to MTD with regular lab monitoring every 4 to 8 weeks. Most adverse effects are mild and manageable (including gastrointestinal upset, nail discoloration, and rare cutaneous ulcers). Dose-dependent neutropenia, anemia, and reticulocytopenia require monitoring but are reversible with dose adjustment.

Pharmacists' Role in Hydroxyurea Management

Despite its benefits, hydroxyurea remains underutilized. Clinicians prescribe it to fewer than 1 in 4 eligible patients in the US, and many do not reach MTD. Barriers include misconceptions about safety, limited access to care, and poor adherence, especially in underserved populations. Pharmacists can address these challenges by providing individualized education, identifying drug interactions, and using telehealth to reach patients in remote or resource-limited settings.

For pharmacists, effective counseling includes setting expectations around adverse effects, stressing the importance of adherence and lab work, and reinforcing hydroxyurea’s ability to prevent serious complications. By actively managing therapy, pharmacists can significantly reduce disease burden and improve quality of life for patients with SCD.

Beyond utilizing hydroxyurea, pharmacists are involved in a multitude of aspects of SCD care. Newer agents with disease-modifying capabilities are continuously in development and being made available, necessitating that pharmacists stay informed about emerging changes to available therapies and patient eligibility criteria. Furthermore, pharmacists are critical in navigating the often-complex regimens necessary for effective SCD care and in preventing therapy duplication.

Coordinating care across a patient’s multidisciplinary team is also crucial. Often, pharmacists communicate with hematologists, social workers, case managers, primary care providers, and a series of other stakeholders to ensure quality, continuous patient care. These communications are essential to ensuring that lesser-known but important aspects of SCD care—such as ensuring patient access to therapy, continuous follow-up, and transportation for appointments—are ensured.

In the overall SCD space, patient education is paramount. Pharmacists are important players in educating patients on currently available treatments, their regimens, and possible adverse event profiles. When a patient with SCD expresses interest in using hydroxyurea, for example, pharmacists are the first step in introducing patients to the medicine and its vast benefits.

REFERENCE

Roessner C, Uminski K, Goodyear D, Rydz N. Clinical consultation: The pharmacist's role in hydroxyurea management for sickle cell disease. Am J Health Syst Pharm. Published online June 12, 2025. doi:10.1093/ajhp/zxaf114. Accessed July 7, 2025.