General Information

Droxia (hydroxyurea) is an antimetabolite.

Droxia is specifically indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises.

Droxia is supplied as capsules for oral administration.

• Initial dose: 15 mg/kg once daily. Monitor the patient’s blood count every two weeks.
• The dose may be increased by 5 mg/kg/day every 12 weeks until a maximum tolerated dose or 35 mg/kg/day is reached if blood counts are in an acceptable range.
• The dose is not increased if blood counts are between the acceptable range and toxic. Discontinue Droxia until hematologic recovery if blood counts are considered toxic. Treatment may then be resumed after reducing the dose by 2.5 mg/kg/day from the dose associated with hematological toxicity.

Mechanism of Action

The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein.

The mechanisms by which Droxia produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. Known pharmacologic effects of Droxia that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.

Side Effects

Adverse effects associated with the use of Droxia may include, but are not limited to, the following:

• hematological
• gastrointestinal symptoms
• anorexia

The Droxia drug label comes with the following Black Box Warning:

• Myelosuppression: Droxia may cause severe myelosuppression. Do not give if bone marrow function is markedly depressed. Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary.
• Malignancies: Droxia is carcinogenic. Advise sun protection and monitor patients for malignancies

Clinical Trial Results

The efficacy of Droxia in sickle cell anemia was assessed in a large clinical study. The study was a randomized, double-blind, placebo-controlled trial that evaluated 299 adult patients with moderate to severe disease (at least 3 painful crises yearly). The trial was stopped by the Data Safety Monitoring Committee, after accrual was completed but before the scheduled 24 months of follow-up was completed in all patients, based on observations of fewer painful crises among patients receiving hydroxyurea. Compared to placebo treatment, treatment with hydroxyurea resulted in a significant decrease in the yearly rate of painful crises, the yearly rate of painful crises requiring hospitalization, the incidence of chest syndrome, the number of patients transfused, and units of blood transfused. Hydroxyurea treatment significantly increased the median time to both first and second painful crises. Although patients with 3 or more painful crises during the preceding 12 months were eligible for the study, most of the benefit in crisis reduction was seen in the patients with 6 or more painful crises during the preceding 12 months.