Hydroxyurea (Hydroxycarbamide)

Indications

Hydroxyurea (Hydroxycarbamide) is used for: Chronic myeloid leukaemia, Psoriasis, Myeloproliferative disorders, Sickle-cell disease, Essential thrombocythemia, AIDS

Adult Dose

Solid Tumors Intermittent Therapy: 80 mg/kg PO q3day, OR Continuous Therapy: 20-30 mg/kg PO qDay Head & Neck Tumors Concomitant therapy with irradiation 80 mg/kg PO q3days Begin 7 days prior to initiation of irradiation Chronic Myelocytic Leukemia, Resistant Continuous Therapy: 20-30 mg/kg PO qDay Sickle Cell Disease Start: 15 mg/kg/day as single dose; monitor patient’s blood count every two weeks Titrate by 5 mg/kg/day q12wk Dose is not increased if blood counts are between acceptable range and toxic Not to exceed 35 mg/kg/day Discontinue therapy until hematologic recovery if blood counts are considered toxic; may resume treatment after reducing dose by 2.5 mg/kg/day from dose associated with hematological toxicity Thrombocythemia, Essential 15 mg/kg PO qDay Titrate to control platelets & maintain WBC count

Child Dose

Oral Sickle-cell disease Child: 1-18 yr: 10-20 mg/kg/day, increased by 5 mg/kg/day every 12 wk according to response and blood counts.

Renal Dose

Renal impairment: Dose reduction may be needed.

Administration

Contra Indications

Severe bone-marrow suppression, severe anaemia, WBC <3000/mm3 or platelet count <100,000/mm3. Pregnancy and lactation. Hypersensitivity.

Precautions

Regular monitoring of uric acid concentrations, blood counts, renal and hepatic function is recommended. Prior irradiation therapy. Elderly. Avoid use of live vaccines. Lactation: excreted in breast milk, do not nurse

Pregnancy-Lactation

Pregnancy No data are available with the use of hydroxyurea in pregnant women Limited available data on hydroxyurea use during pregnancy are insufficient to inform drug-associated risks In case of an exposure to hydroxyurea of pregnant female patients or pregnant partners of male patients, treated by hydroxyurea, a careful follow-up with adequate clinical, biological and ultrasonographic examinations should be considered Based on findings in animals and humans, male fertility may be compromised by treatment; azoospermia or oligospermia has been observed in men; before initiating therapy, inform male patients about the possibility of sperm conservation Advise pregnant women of the potential risk to a fetus; verify the pregnancy status of females of reproductive potential prior to initiating therapy Advise females of reproductive potential to use effective contraception during and after treatment for at least 6 months after therapy; advise males of reproductive potential to use effective contraception during and after treatment for at least 1 year after therapy Animal data In animal reproduction studies, hydroxyurea administration to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m² basis In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae Lactation Unknown whether hydroxyurea is excreted in human milk, the effects of hydroxyurea on the breastfed child, or the effects of hydroxyurea on milk production Because of the potential for serious adverse reactions in a breastfed child from hydroxyurea, including carcinogenicity, advise patients not to breastfeed during treatment

Interactions

Impairs immune response to vaccines; possible infection with live vaccines, zidovudine, zalcitabine. May alter action of oral anticoagulants and phenytoin. Potentially Fatal: Fluorouracil may increase potential for neurotoxicity. Modulates metabolism and cytotoxicity of cytarabine. May precipitate didanosine- or stavudine-induced pancreatitis, hepatotoxicity or neuropathy.

Adverse Effects

Side effects of Hydroxyurea (Hydroxycarbamide) : GI disturbances, Nausea, Vomiting, Constipation, Diarrhea, Hyperuricemia, Renal failure, Rash, Hyperpigmentation. Pulmonary oedema, dermatological reactions, headache, dizziness. Disorientation, drowsiness, hallucinations, convulsions, alopecia. Potentially Fatal: Bone marrow suppression.

Mechanism of Action

Hydroxycarbamide causes inhibition of DNA synthesis during the S-phase of cell division by acting as a ribonucleotide reductase inhibitor resulting to cell death. It is S-phase specific.