hydroxyurea
Table of Contents
hydroxyurea
see also:
Introduction
- hydroxurea is an oral anti-metabolite medication used to Rx certain bone marrow disorders such as myeloproliferative diseases (polycythaemia rubra vera, essential thrombocytosis), sickle cell disease (SCD), CML (but now replaced by imatinib), systemic mastocytosis with associated hematological neoplasm(SM-AHN), and as a 2nd line agent in psoriasis
- also known as hydroxycarbamide
- endogenous in human blood plasma at concentrations of approximately 30 to 200 ng/ml
- marketed in Australia as Hydrea
- in patients with myeloproliferative diseases who are intolerant of hydroxyurea or fail to respond, a JAK 1/2 inhibitor such as ruxolitinib may be an option
Adult dosage
- tablets are usually 500mg and should be should be handled with care and wash hands after touching them. People who are not taking this medicine should avoid touching it.
- usual dose is 15mg/kg/day (in reality for adults this is 500mg/day for most as they should NOT be crushed or divided)
- adjust if renal impairment
- take with or after meals
- in myeloproliferative diseases (usually those aged over 50yrs and prescribed and monitored monthly initially by a haematologist):
- usual starting dose is 500mg / day and adjust as needed according to response - some may need one every two days, others may need increasing to 1000mg/day.
Mechanisms of action
- decreases the production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals as they are involved in the reduction of nucleoside diphosphates (NDPs)
- causes production of reactive oxygen species in cells, leading to disassembly of replicative DNA polymerase enzymes and arresting DNA replication
- in sickle cell disease (SCD), it increases the concentration of fetal hemoglobin
- also inhibits cytochrome P-450 CYP2D6
Adverse effects
- bone marrow suppression
- dose-limiting toxicity - may take 7–21 days to recover after the drug has been discontinued
- fevers
- gastro-intestinal
- loss of appetite
- psychiatric problems
- shortness of breath
- headaches
- abnormal LFTs
- raised serum creatinine and uric acid levels
- skin rashes
- may increase the risk of later cancers
Contra-indications
- pregnancy
- lactation
- severe anaemia
- leukopenia
- thrombocytopenia
- Live vaccines should not be given to people on hydroxyurea
- Handle tablets with care and wash hands and any contaminated surfaces carefully
- Patients with raised serum uric acid levels should be Rx with allopurinol (with acute gout prophylactic cover on starting as usual)
hydroxyurea.txt · Last modified: 2025/07/03 02:14 by gary1