The efficacy of hydroxyurea in sickle cell anemia was assessed in a large clinical study (Multicenter Study of Hydroxyurea in Sickle Cell Anemia).1
The study was a randomized, double-blind, placebo-controlled trial that evaluated 299 adult patients (≥18 years) with moderate to severe disease (≥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.
| PERCENT CHANGE|
|* A painful crisis was defined in the study as acute sickling-related pain that resulted in a visit to a medical facility, that lasted more than 4 hours, and that required treatment with a parenteral narcotic or NSAID. Chest syndrome, priapism, and hepatic sequestration were also included in this definition.|
|Median yearly rate of painful crises*||2.5||4.6||-46||=0.001|
|Median yearly rate of painful crises requiring hospitalization||1.0||2.5||-60||=0.0027|
|Median time to first painful crisis (months)||2.76||1.35||+104||=0.014|
|Median time to second painful crisis (months)||6.58||4.13||+59||=0.0024|
|Incidence of chest syndrome (# episodes)||56||101||-45||=0.003|
|Number of patients transfused||55||79||-30||=0.002|
|Number of units of blood transfused||423||670||-37||=0.003|
No deaths were attributed to treatment with hydroxyurea, and none of the patients developed neoplastic disorders during the study. Treatment was permanently stopped for medical reasons in 14 hydroxyurea-treated (2 patients with myelotoxicity) and 6 placebo-treated patients. (See ADVERSE REACTIONS.)
In patients with SCA treated with hydroxyurea, fetal hemoglobin (HbF) increases 4 to 12 weeks after initiation of treatment. In general, average HbF levels correlate with dose and plasma level with possible plateauing at higher dosages.
A clear relation between reduction in crisis frequency and increased HbF or F-cell levels has not been demonstrated. The dose-related cytoreductive effects of hydroxyurea, particularly on neutrophils, was the factor most strongly correlated with reduced crisis frequency.
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed.
DROXIA is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
- Charache S, Barton FB, Moore RD, et al; Hydroxyurea and sickle cell anemia: clinical utility of a myelosuppressive “switching” agent. Medicine. 1996;75:300-326.
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Rev December 2006
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