DRUG INTERACTIONS
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.
EVENT
|
HYDROXYUREA
(N=152)
|
PLACEBO
(N=147)
|
PERCENT
CHANGE
VS PLACEBO
|
P-VALUE
|
| * 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.)
Fetal Hemoglobin
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.
|
