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Availability:
  • Capsule Hydroxyurea 500mg
  • for lower doses (syrup), preparations need to be sent to HWKKS for manufacturing as it is cytotoxic
  • Current stability of preparation is at 2 weeks
Mechanism of action
  • Hydroxyurea therapy is associated with an improvement in the ineffective erythropoiesis, as reflected by an increase in the Hb level, a reduction in red cell transfusion requirement and a decreasing trend in the serum lactate dehydrogenase (LDH) and serum unconjugated bilirubin levels.
  • This favourable effect of hydroxyurea was observed as early as one to three months post treatment.
  • In contrast, a significant decrease in spleen size reflecting a reduction in extramedullary erythropoiesis appeared to take place much later, after six months of hydroxyurea therapy with a maximal benefit observed at 12 months of therapy.
  • These favourable effects of hydroxyurea appeared to be associated with an increase in the γ-globin biosynthesis, because the percentage of HbF increased as well as the total Hb.
Dosing
  • There are no clear guidelines in terms of dose or duration of use
  • Most practice/studies use an initiation dose of 10 mg/kg/day
  • Some do practice initiation at a lower dose of 5mg/kg/day and tapered upwards.
  • Doses can be optimized up to 15-20 (35) /mg/kg/day
  • Doses can be increased by 5 mg/kg per day every 4-6 weeks until toxicity or according to clinical response or total dose 35mg/kg/day
  • In some study, toxicity was not considerable even at maximal doses (10-15 mg/kg)
Monitoring
  • If at any time they showed intolerance or their laboratory tests show leucopenia or decreased platelet count, deranged RFTs or LFTs, the drug was discontinued temporarily and restarted at lower dose and increased again till the desired effect is achieved.
  • Patients were also be monitored for treatment response and side effects of HU.
  • Treatment response was defined as the ability to maintain hemoglobin above 9g/dl or reduction of at least 50% of baseline transfusion requirements
  • According to response to treatment the patients were categorized as /good responders (if they did not require transfusion after treatment or their transfusion interval increased more than 50% of the pre-therapy), partial responders (declined transfusion requirement i.e. less than 20%, or decrease in size of liver and spleen or improvement in well being), poor responders (transfusion requirement not declined).
  • In the rare instances of leucopenia or thrombocytopenia temporary discontinuation of the drug resulted in rapid normalization of the cell count and allowed resumption of therapy.
  • Alleviation of clinical symptoms such as loss of energy, fatigue, and depression after HU therapy, may also be explained by the increased transfusion intervals.
References
  1. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012064/full
  2. http://thalassemia.com/treatment-hu.aspx#gsc.tab=0
  3. Hydroxyurea Treatment in Beta-Thalassaemia Intermedia. HK J Paediatr (new series) 2006;11:20-21
  4.  Treatment Response to Hydroxyurea  in Beta Thalassemia.  Journal of Islamabad Medical & Dental College (JIMDC); 2014:3(2):48-52
  5. Hydroxyurea Can Reduce or Eliminate Transfusion Requirements in Children with Major and Intermediate Thalassemia. IJBC 2009; 4: 147-150
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173031/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102988/
  8. http://mji.ui.ac.id/journal/index.php/mji/article/view/259

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