Hydrea 500 mg (Hydroxyurea)

Description

COMPOSITION
HYDREA capsule: Each capsule contains Hydroxyurea USP 500 mg.
PHARMACOLOGY
Hydroxyurea is converted to a free radical nitroxide (NO) in vivo. and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (SGC) by hydroxyurea-derived NO.
Pharmacokinetic
Absorption: Oral administration of Hydroxyurea reaches peak plasma concentrations in 1 to 4 hours. There are no data on the effect of food on the absorption of Hydroxyurea.
Distribution: Hydroxyurea distributes throughout the body with a volume of distribution approximating total body water.
Metabolism: Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation by urease found in intestinal bacteria.
Excretion: In patients with sickle cell anemia, the mean cumulative urinary recovery of Hydroxyurea was about 40% of the administered dose.
INDICATIONS AND USAGE
Hydroxyurea is indicated for the treatment of:
• Polycythaemia vera
Essential thrombocythemia Sickle cell anemia
Resistant chronic myeloid leukemia
• Locally advanced squamous cell carcinomas of the head and neck in combination with chemoradiation
DOSAGE AND ADMINISTRATION
Polycythaemia Vera: Administer 15-20 mg/kg orally once daily.
Essential Thrombocythemia: Administer 15 mg/kg orally once daily.
Solid Tumors
Intermittent Therapy: Administer 80 mg/kg orally every three days.
Continuous Therapy: Administer 20-30 mg/kg orally once daily (qDay)
Head & Neck Tumors: Start 80 mg/kg orally every three days (q3days) seven days before initiating irradiation.
Chronic Myelocytic Leukemia, Resistant: Administer 20-40 mg/kg orally once daily.