From the Guidelines
Hydroxyurea is a crucial medication in the management of sickle cell disease, particularly for patients with the HbSS genotype, as it significantly reduces the frequency of painful crises, acute chest syndrome, and the need for blood transfusions, ultimately improving morbidity, mortality, and quality of life. In sickle cell disease, hydroxyurea works by increasing fetal hemoglobin production, which prevents red blood cells from sickling. The typical adult dose ranges from 15-35 mg/kg/day, with treatment requiring regular blood count monitoring due to potential bone marrow suppression, as noted in studies such as 1.
Key Benefits and Considerations
- Hydroxyurea has been shown to decrease hospitalizations, episodes of vaso-occlusive crises (VOC), and episodes of acute chest syndrome (ACS) in patients with sickle cell disease, as demonstrated in trials like the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) trial 1.
- It is indicated for patients with SCD who have the HbSS genotype and at least three VOC per year or at least one episode of ACS, with the recommendation being strong due to the certain desirable effects outweighing the undesirable effects in the intended population 1.
- The medication's effectiveness in improving health-related quality of life in people with HbSS or Sb0-thalassemia is well-documented, with benefits seen in social function and general health perception 1.
- Side effects include bone marrow suppression, gastrointestinal issues, skin changes, and rarely skin ulcers, necessitating careful monitoring and dose adjustments as needed.
Cancer Treatment
In the context of cancer, hydroxyurea functions as an antimetabolite that inhibits DNA synthesis by blocking ribonucleotide reductase, making it effective for chronic myeloid leukemia, polycythemia vera, and essential thrombocythemia. Cancer dosing varies by condition but typically ranges from 500-3000 mg daily. The choice of hydroxyurea in cancer treatment is based on its ability to disrupt cancer cell replication in malignancies, similar to its mechanism in promoting healthier hemoglobin in sickle cell disease.
Monitoring and Safety
Regular monitoring of blood counts is essential due to the potential for bone marrow suppression. The medication's safety profile, including the risk of neutropenia and other adverse effects, is well-characterized, with studies showing that these effects can often be managed with dose adjustments or temporary discontinuation of therapy 1.
Given the most recent and highest quality evidence, hydroxyurea should be considered a first-line treatment for eligible patients with sickle cell disease, given its proven benefits in reducing morbidity and improving quality of life, as supported by guidelines and studies such as 1 and 1.
From the FDA Drug Label
INDICATIONS AND USAGE Hydroxyurea capsules are an antimetabolite indicated for the treatment of: Resistant chronic myeloid leukemia. (1) Locally advanced squamous cell carcinomas of the head and neck, (excluding lip) in combination with concurrent chemoradiation. (1)
The role of Hydroxyurea in managing sickle cell disease is not mentioned in the provided drug labels. However, Hydroxyurea is indicated for the treatment of certain types of cancer, including:
- Resistant chronic myeloid leukemia
- Locally advanced squamous cell carcinomas of the head and neck (in combination with concurrent chemoradiation) 2
No conclusion can be drawn regarding the use of Hydroxyurea in managing sickle cell disease based on the provided information.
From the Research
Role of Hydroxyurea in Sickle Cell Disease
- Hydroxyurea is a myelosuppressive agent that has been proven to reduce the frequency of painful episodes in sickle cell disease by 50% 3.
- It raises the level of HbF and the haemoglobin level, and decreases the rate of ACS episodes and blood transfusions by ~50% in adults 3.
- Hydroxyurea is the only approved drug for the treatment of sickle cell disease, and it has been shown to be effective in adults with the disease 4.
- The evidence suggests that hydroxyurea may impair spermatogenesis, but it is not associated with leukemia in adults with sickle cell disease 4.
Role of Hydroxyurea in Cancer
- Hydroxyurea was developed as an anticancer drug and has been used to treat myeloproliferative syndromes, leukemia, melanoma, and ovarian cancer 3.
- It has been approved by the FDA for use in adults, but its use in cancer treatment is not as well-studied as its use in sickle cell disease.
Current Status of Hydroxyurea in Sickle Cell Disease Management
- Despite the development of new therapeutics, hydroxyurea remains the gold standard for the treatment of sickle cell disease 5.
- Hydroxyurea is not only a disease modifier, but it also has additional clinical benefits, and its affordability and longevity have prompted expanded research in areas such as underutilization and pharmacogenomics 5.
- The role of hydroxyurea in sickle cell disease management is evolving, and it continues to be a key agent in disease management 5.
Comparison with Other Therapies
- Hydroxyurea has been compared to other therapies, including phlebotomy, transfusion, and chelation, and it has been shown to be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia 6.
- However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose 6.
- Newer agents, such as l-glutamine, crizanlizumab, and voxelotor, have been approved by the FDA for use in SCD patients, but their clinical and economic impacts are still being evaluated 7.