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Hydroxyurea Use in Sickle Cell Disease

Role, indications, pharmacodynamics of hydroxyurea

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bensoul
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37 views19 pages

Hydroxyurea Use in Sickle Cell Disease

Role, indications, pharmacodynamics of hydroxyurea

Uploaded by

bensoul
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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HYDROXYUREA USE IN

SICKLE CELL DISEASE

Name: Dr Alice Gichemi


Paediatric Hematology and Oncology Fellow
Pathophysiology

2
Mode of Action
• Fetal hemoglobin induction
• lower ANC and retic counts
• Decreased adhesiveness
• Reduced hemolysis
• Nitric oxide (NO) release

3
Benefits
• Increased Hemoglobin F%
• Reduced ‘sticky’ WBC and Platelet counts
• Raised Hemoglobin value
• Enhanced Nitric Oxide

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Ideal drug
1.single-agent, inexpensive, orally administered, once-daily dosing

2.Laboratory efficacy: increases HbF and total Hb, reduces WBC


and reticulocytes, and lowers LDH

3.Clinical efficacy: ameliorates anemia, leads to fewer vaso


occlusive events and hospitalizations, decreases hemolysis

4.Treatment goals: works in all age groups, prevents acute events


and chronic organ dysfunction
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5.Sustainability: benefits continue over time without
medication resistance or tolerance

6. Side effects: few short-term toxicities that might limit


adherence, wide therapeutic index

7. Safety: no major short-term toxicities, plus no known


long-term sequelae or complications of therapy.

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Studies/Trials

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The Multicenter Study of Hydroxyurea

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BabyHUG Trial
• 9-18 months of age with sickle cell anemia.
• n=193
• lower rates of initial and recurrent episodes of pain, dactylitis, acute
chest syndrome, and hospitalization
• infants who were asymptomatic at enrollment had less dactylitis as
well as fewer hospitalizations and transfusions if treated with
hydroxyurea.
• Despite expected mild myelosuppression, hydroxyurea was not
associated with an increased risk of bacteremia or serious infection.

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HUSOFT Results
• feasibility of hydroxyurea in children with SCA-ages of 6 -24 months
• n=28
• fixed hydroxyurea dose of 20 mg/kg/d was well tolerated with few
hematologic toxicities.
• No additional toxicities in extension studies with dose escalation to
MTD.

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…HUSOFT
• HU was associated with
• increased HB, HbF, MCV,
• decreased reticulocytes, (WBCs), and plt (P < .01).
• Patients experienced 7.5 acute chest syndrome (ACS) events
per 100 person-years, compared with 24.5 events per 100
person-years among historic controls (P = .001).
• Had better spleen function than expected and improved
growth rates

11
Long-term safety and efficacy
Sustained benefits

• Laboratory benefits are sustained when children with SCA


are adherent with therapy.
• HUSOFT- growth and development, splenic function
• Fewer painful events and hospitalizations.
• For adults in MSH, long-term exposure to hydroxyurea was
associated with significantly reduced mortality and improved
quality of life.
• Lowers TCD velocity

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Adverse Effects
• Mild, Transient, Reversible,
• Myelosuppression- Neutropenia, thrombocytopenia
• GI disturbances, Abd discomfort, nausea
• Dermatological changes- Hyperpigmentation,
melanonychia

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Who gets Hydroxyurea

• Approved to be started in Children at 9 months.


• Adults…as per current guideline or all?

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Dosing
• Available as 500 mg capsules/tablets
• May be compounded to a liquid formulation
• Start at at 20mg/kg/day for children; 15 mg/kg/day for adults
• calculate the total weekly dose and divide up
• Dose escalation 5 mg/kg/day every 2-3 months, and the maximum
recommended dose is 35 mg/kg/day;
• maintaining Neutrophils count 2x 1000/mm3
• If myelosuppression occurs:
• Counts should recover 2 weeks after discontinuing the drug
• Restart at a dosage 5 mg/kg/day less than the previous dose

Ware RE, et al. Hematol Am Soc Hematol Educ Program. 2015; 436-443
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IMPORTANT
• ADHERANCE!!!!
• Patient education
• GO OVER medication at each visit
• Adherance helpers: Alarms, caregiver reminders, Pill
boxes, response images

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Take home messages:
• Hydroxyurea is effective in improving
symptoms,reducing hospitalization and its financial
burden, preventing long term sequelae, improving
quality of life and overall mortality

• Advocate to have drug available in the county pharmacy


for pts to use NHIF

18
Questions?

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