Droxia (Hydroxyurea) - Indications and Dosage

INDICATIONS AND USAGE

DROXIA (hydroxyurea capsules, USP) is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months).

DOSAGE AND ADMINISTRATION

Procedures for proper handling and disposal of cytotoxic drugs should be considered. Several guidelines on this subject have been published.^2-5

To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing DROXIA capsules. DROXIA capsules should not be opened. Personnel should avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. More information is available in the references listed below.

Dosage should be based on the patient’s actual or ideal weight, whichever is less. The initial dose of DROXIA is 15 mg/kg/day as a single dose. The patient’s blood count must be monitored every two weeks. (See WARNINGS.)

If blood counts are in an acceptable range*, the dose may be increased by 5 mg/kg/day every 12 weeks until a maximum tolerated dose (the highest dose that does not produce toxic** blood counts over 24 consecutive weeks), or 35 mg/kg/day, is reached.

If blood counts are between the acceptable range* and toxic**, the dose is not increased.

If blood counts are considered toxic**, DROXIA should be discontinued until hematologic recovery. Treatment may then be resumed after reducing the dose by 2.5 mg/kg/day from the dose associated with hematologic toxicity. DROXIA may then be titrated up or down, every 12 weeks in 2.5 mg/kg/day increments, until the patient is at a stable dose that does not result in hematologic toxicity for 24 weeks. Any dosage on which a patient develops hematologic toxicity twice should not be tried again.

          *acceptable range =
                    neutrophils ≥2500 cells/mm³,
                    platelets ≥95,000/mm³,
                    hemoglobin >5.3 g/dL and
                    reticulocytes ≥95,000/mm³ if the hemoglobin concentration <9 g/dL.

          **toxic =
                    neutrophils <2000 cells/mm³,
                    platelets <80,000/mm³,
                    hemoglobin <4.5 g/dL and
                    reticulocytes <80,000/mm³ if the hemoglobin concentration <9 g/dL.

Since hydroxyurea may raise the serum uric acid level, dosage adjustment of uricosuric medication may be necessary.

Renal Insufficiency

As renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of DROXIA in patients with renal impairment. The results of a single-dose study of the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease suggest that the initial dose of hydroxyurea should be reduced by 50%, to 7.5 mg/kg/day, when used to treat patients with renal impairment. (See PRECAUTIONS and CLINICAL PHARMACOLOGY.) Close monitoring of hematologic parameters is advised in these patients.

*On dialysis days, hydroxyurea should be administered to patients with ESRD following hemodialysis.
Creatinine Clearance (mL/min)	Recommended DROXIA Initial Dose (mg/kg daily)
≥60	15
<60 or ESRD*	7.5

Hepatic Insufficiency

There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.

HOW SUPPLIED

DROXIA^® (hydroxyurea capsules, USP).

200 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6335-17). The cap and body are opaque blue-green. The capsule is marked in black ink on both the cap and body with “DROXIA” and “6335”.

300 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6336-17). The cap and body are opaque purple. The capsule is marked in black ink on both the cap and body with “DROXIA” and “6336”.

400 mg capsules packaged in HDPE bottles of 60 with a plastic safety screw cap. (NDC 0003-6337-17). The cap and body are opaque reddish-orange. The capsule is marked in black ink on both the cap and body with “DROXIA” and “6337”.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Keep tightly closed.