Active ingredient: Hydroxyurea - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antisickling Agents
• Antineoplastic Agents

Dosage Forms

• Capsule

Brands / Synonyms

Biosupressin; Carbamohydroxamic Acid; Carbamohydroximic Acid; Carbamohydroxyamic Acid; Carbamoyl Oxime; Carbamyl Hydroxamate; Droxia; Hidrix; HU; Hydrea; Hydreia; Hydroxicarbamidum; Hydroxycarbamide; Hydroxycarbamine; Hydroxylurea; Hydroxyurea; Hydura; Hydurea; Idrossicarbamide [Dcit]; Litaler; Litalir; N-Carbamoylhydroxylamine; N-Hydroxyurea; Onco-Carbide; Oxyurea; Sterile Urea; Ureaphil

Indications

For management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia.

Pharmacology

Hydroxyurea has dose-dependent synergistic activity with cisplatin in vitro. In vivo Hydroxyurea showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Hydroxyurea was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to Hydroxyurea 4 hours before cisplatin produced the greatest interaction.

Mechanism of Action

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.

Absorption

Well absorbed from the gastrointestinal tract.

Toxicity

Oral, mouse: LD₅₀ = 7330 mg/kg; Oral, rat: LD₅₀ = 5760 mg/kg Teratogenicity: Teratogenic effects have occurred in experimental animals.Hydroxyurea use during a small number of human pregnancies has been reported. Adverse effects have not been observed in any of the exposed newborns. Reproductive Effects: Adverse reproductive effects have occurred in experimental animals. Mutagenicity: Mutagenic effects have occurred in experimental animals.Mutagenic effects have occurred in humans.

Biotrnasformation / Drug Metabolism

Hepatic.

Contraindications

Hydroxyurea is contraindicated in patients with marked bone marrow depression, i.e., leukopenia (<2500 WBC) or thrombocytopenia (<100,000), or severe anemia.

HYDREA is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.

Drug Interactions

Prospective studies on the potential for hydroxyurea to interact with other drugs have not been performed.

Concurrent use of hydroxyurea and other myelosuppressive agents or radiation therapy may increase the likelihood of bone marrow depression or other adverse events.

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