Information about Hydroxyurea
Hydroxyurea is an antimetabolite that is used in the treatment of cancer and to stimulate fetal hemoglobin production in sickle cell disease.
Liver safety of Hydroxyurea
Hydroxyurea is associated with a low rate of transient serum enzyme and bilirubin elevations during therapy, and has been implicated in rare cases of clinically apparent acute liver injury with jaundice.
Mechanism of action of Hydroxyurea
Hydroxyurea (hye drox” ee ure ee’ a) is a hydroxylated analogue of urea and an antimetabolite which inhibits the enzyme ribonucleotide reductase, which is necessary for DNA synthesis and cell cycle replication. Blocking the enzyme results in cell cycle arrest in the S phase, but does not interfere with RNA or protein synthesis. Hydroxyurea is used in the treatment of solid tumors and myeloproliferative diseases, the latter because of its effects in reducing excessive production of red blood cells (polycythemia vera), white blood cells (chronic myelogenous leukemia) or platelets (essential thrombocythemia). Hydroxyurea also increases the production of fetal hemoglobin, via an unknown mechanism of action, which increases overall hemoglobin levels and decreases sickling in patients with sickle cell anemia. In controlled clinical trials, hydroxyurea has been shown to increase hemoglobin concentrations, decrease transfusion requirements and lessen painful crises in patients with sickle cell disease.
FDA approval information for Hydroxyurea
Hydroxyurea was first approved for use in the United States in 1967 as an antineoplastic agent for therapy of melanoma, chronic myelogenous leukemia, ovarian carcinoma, and head and neck cancers. The indications were expanded to sickle cell disease in 1998, which is the major indication for its use at present.
Dosage and administration for Hydroxyurea
Hydroxyurea is available in capsules of 200, 300, 400 and 500 mg generically and under brand names as Droxia (for sickle cell disease) and Hydrea (for cancer). The usual dose in sickle cell disease is 15 mg/kg/day, with subsequent dose adjustments based upon efficacy and tolerance. Higher doses are used in cancer chemotherapy.
Side effects of Hydroxyurea
Common side effects include bone marrow suppression (particularly thrombocytopenia), nausea, vomiting, anorexia, diarrhea, mucositis, hair loss, headache, rash and fever. Uncommon, but potentially severe adverse reactions include severe skin ulcers, neuropathy, renal dysfunction, severe bone marrow suppression and pulmonary fibrosis. Long term hydroxyurea therapy may increase the risk of cancer.