What are the recommended eltrombopag dosing and monitoring guidelines for an adult with chronic immune thrombocytopenia, a child aged 2 years or older, and a patient with severe aplastic anemia (including dose adjustments for patients of East Asian descent)?

Eltrombopag Dosing and Monitoring Guidelines

Chronic Immune Thrombocytopenia (ITP) in Adults

For adults with chronic ITP who have failed corticosteroids or are at risk of bleeding after splenectomy, initiate eltrombopag at 50 mg once daily, with dose adjustments to maintain platelet counts ≥50 × 10⁹/L, not exceeding 75 mg daily. 1, 2

Initial Dosing

• Start at 50 mg once daily for most adult patients 1, 2
• Reduce to 25 mg once daily for patients of East Asian ancestry (including Chinese, Japanese, Korean, Taiwanese) 2
• Take on an empty stomach or with a low-calcium meal (≤50 mg calcium) 2
• Administer at least 2 hours before or 4 hours after polyvalent cations (antacids, calcium-rich foods, mineral supplements) 2

Dose Titration

• Monitor platelet counts weekly until stable count achieved 3
• If platelet count remains <50 × 10⁹/L after 2-3 weeks, increase dose by 25 mg increments 1
• Maximum dose: 75 mg daily for ITP 1, 2
• By day 15, more than 80% of patients receiving 50-75 mg daily show platelet count increases 1

Response Rates

• 70% response rate at 50 mg dose (platelet count >50 × 10⁹/L) 1
• 81% response rate at 75 mg dose 1
• Platelet responses typically occur within 1-2 weeks 1, 4

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Pediatric ITP (Age 2 Years and Older)

Initiate eltrombopag at 25 mg once daily for children aged 2-5 years and 50 mg once daily for children aged 6 years and older, adjusting to maintain platelet counts ≥50 × 10⁹/L. 2

Age-Based Dosing

• Ages 2-5 years: Start at 25 mg once daily 2
• Ages 6 years and older: Start at 50 mg once daily (same as adults) 2
• East Asian children: Reduce initial dose by 50% 2

Monitoring

• Weekly platelet counts until stable 3
• Monthly monitoring once stable response achieved 3

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Severe Aplastic Anemia (SAA)

For refractory severe aplastic anemia, initiate eltrombopag at 50 mg once daily (or 25 mg for East Asian patients), titrating up to 150 mg daily as needed to maintain platelet counts >50 × 10⁹/L, with a maximum dose of 150 mg daily. 2, 5, 6

Initial Dosing

• Start at 50 mg once daily for most patients 2, 5
• 25 mg once daily for East Asian ancestry patients 2
• Can increase to 150 mg daily as needed 2, 5, 6
• Maximum dose: 150 mg daily 2

Efficacy in SAA

• 44% overall hematologic response rate at 12 weeks in refractory SAA 5
• Multilineage responses observed: 9 patients achieved platelet transfusion independence, 6 improved hemoglobin levels, 9 increased neutrophil counts 5
• When combined with ATG as first-line therapy, 90% overall response rate with 50% complete response 6

SAA-Specific Monitoring

• Serial bone marrow biopsies to assess trilineage hematopoiesis 5
• Monitor for clonal karyotypic aberrations (occur in 10-20% of SAA patients on eltrombopag) 6

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Critical Monitoring Requirements

Platelet Count Monitoring

• Weekly until stable platelet count achieved 3
• Monthly once stable 3
• Target range: 50-200 × 10⁹/L 7

Liver Function Tests

• Baseline liver function tests mandatory 3, 8
• Regular monitoring during treatment (13% develop liver function abnormalities) 1, 8
• Use with extreme caution in preexisting liver disease 8

Additional Safety Monitoring

• Bone marrow reticulin (increased reticulin reported) 1
• Thrombotic events (treatment-related serious adverse event) 1
• Worsening thrombocytopenia upon discontinuation 1

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Dose Adjustments and Special Populations

Hepatic Impairment

• Dose reductions required for hepatic impairment 2
• Close monitoring essential given 13% baseline hepatotoxicity risk 8

East Asian Ancestry

• Reduce initial dose by 50% for patients of East/Southeast Asian ancestry 2
• This applies to all indications (ITP, pediatric ITP, SAA) 2

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Treatment Duration and Discontinuation

Sustained Response

• Responses sustained up to 1.5 years with continuous administration in ITP 1
• Up to 3 years safe and well-tolerated in Japanese patients 7
• Up to 4 years with continuous administration reported 1

Tapering Criteria

• Consider tapering in patients with stable platelet counts (50-100 × 10⁹/L) for ≥6 months without concomitant treatments 3
• Patients on anticoagulation require platelet count ≥100 × 10⁹/L before tapering 3
• 3-48% of patients maintain response after discontinuation 3

Relapse Management

• If relapse occurs, re-introduce at minimum effective dose 3
• Platelet counts typically return to baseline within 2 weeks after discontinuation 4

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Critical Pitfalls to Avoid

Drug-Food Interactions

• Never take with calcium-rich foods (significantly reduces absorption) 3, 2
• Maintain strict 2-hour before/4-hour after window for polyvalent cations 2

Dose Management

• Avoid abrupt interruptions or excessive dose adjustments (causes platelet fluctuations) 3
• Do not exceed maximum doses: 75 mg for ITP, 150 mg for SAA 2

Bleeding Risk

• Bleeding episodes decreased from 63% at baseline to 21% after 2 weeks of treatment 7
• Patients receiving eltrombopag had significantly less bleeding than placebo (OR 0.49, p=0.021) 4