What are the recommended clinical practices for using romiplostim and eltrombopag in chronic immune thrombocytopenia, including initial dosing, titration schedules, maximum doses, dose reduction strategies, required baseline laboratory evaluations, and ongoing monitoring parameters?

Clinical Use of Romiplostim and Eltrombopag in ITP

Initial Dosing

Romiplostim should be initiated at 1 mcg/kg subcutaneously once weekly, while eltrombopag should be started at 36 mg orally once daily for most adult patients with chronic ITP. 1, 2

Romiplostim Starting Dose

• Standard initial dose: 1 mcg/kg subcutaneously once weekly 1
• Higher initial doses (2-4 mcg/kg) are commonly used in clinical practice for severe thrombocytopenia, with evidence suggesting faster platelet responses at 2-3 mcg/kg 3, 4
• Pediatric patients ≥1 year: Same 1 mcg/kg weekly dosing 1

Eltrombopag Starting Dose

• Standard initial dose: 36 mg orally once daily 2
• Reduced initial dose of 18 mg daily for patients with hepatic impairment 2
• Reduced initial dose for patients of East/Southeast Asian ancestry 2
• Pediatric patients ≥6 years: 36 mg once daily 2

Dose Titration and Adjustment

Romiplostim Titration

• Adjust dose weekly by 1 mcg/kg increments to achieve and maintain platelet count ≥50 × 10⁹/L 1
• Clinical practice data suggests larger dose increments may be safe and achieve faster responses 4
• Dose range: 1-10 mcg/kg weekly 5, 1
• Response typically occurs within 1-4 weeks 5
• 51% of patients achieve platelet count ≥50 × 10⁹/L by end of week 1 with median dose of 2.4 mcg/kg 4

Eltrombopag Titration

• Adjust dose in 18 mg increments every 2 weeks to achieve platelet count ≥50 × 10⁹/L 2
• Available doses: 18 mg, 36 mg, 54 mg tablets 2
• Initial dose of 25 mg daily effectively achieves target platelet counts in many patients 6
• Response typically occurs by day 15 in >80% of patients receiving 50-75 mg doses 5

Maximum Doses

Romiplostim

• Maximum dose: 10 mcg/kg weekly for ITP 1, 5
• Do not exceed this dose even if platelet response is inadequate 1

Eltrombopag

• Maximum dose for ITP: 54 mg daily 2
• Maximum dose for chronic hepatitis C: 72 mg daily 2
• Maximum dose for severe aplastic anemia: 108 mg daily 2

Dose Reduction and Discontinuation

When to Reduce Dose

• Reduce dose if platelet count exceeds 200-400 × 10⁹/L 1, 2
• For stable responses maintained ≥6 months, consider tapering 7

Romiplostim Dose Reduction

• Reduce by 1 mcg/kg weekly 1
• If platelet count >400 × 10⁹/L, withhold dose and resume at reduced dose when platelets <200 × 10⁹/L 1

Eltrombopag Dose Reduction

• Reduce by 18 mg decrements 2
• Low-dose maintenance with 25 mg twice weekly or 25 mg daily effectively maintains target platelet counts 6

Discontinuation Considerations

• Most patients (83-90%) experience platelet count decline upon discontinuation, returning to baseline within 2-4 weeks 5, 6
• Approximately 30% of patients achieve sustained treatment-free remission lasting ≥6 months 7, 8
• 10% may transiently fall below baseline platelet counts after stopping 5
• Median relapse-free survival after eltrombopag discontinuation is 15 days 6

Pre-Treatment Testing

Required Baseline Evaluations

• Complete blood count with platelet count (general medical knowledge)
• Comprehensive metabolic panel including liver function tests (ALT, AST, bilirubin) 2
• Peripheral blood smear to confirm ITP diagnosis (general medical knowledge)
• Hepatitis B and C screening 2
• Consider baseline bone marrow examination if diagnosis uncertain (general medical knowledge)

Eltrombopag-Specific Baseline Testing

• Liver function tests are mandatory before initiating eltrombopag 2
• Screen for hepatic impairment to determine appropriate starting dose 2
• Assess East/Southeast Asian ancestry for dose adjustment 2

Monitoring During Therapy

Platelet Count Monitoring

• Monitor CBC with platelet count weekly during dose titration phase 1, 2
• Once stable dose achieved, monitor platelet counts monthly 1, 2
• More frequent monitoring if dose adjustments made 1, 2

Liver Function Monitoring

• For eltrombopag: Monitor ALT, AST, and bilirubin every 2 weeks during dose titration, then monthly once stable 2
• Liver function test abnormalities occur in 13% of eltrombopag-treated patients 5
• Discontinue eltrombopag if ALT increases ≥3× upper limit of normal with evidence of hepatic dysfunction 2
• Romiplostim requires less intensive liver monitoring but baseline and periodic assessment recommended 1

Bone Marrow Monitoring

• Increased bone marrow reticulin has been reported in >10 patients treated with romiplostim and 7 patients with eltrombopag 5
• Consider bone marrow examination if new cytopenias develop or peripheral blood smear shows abnormalities 5
• Routine bone marrow monitoring is not currently recommended but long-term studies are ongoing 5

Thrombosis Risk Monitoring

• Monitor for signs/symptoms of thrombotic/thromboembolic complications 1, 2
• Portal vein thrombosis reported in patients with chronic liver disease 1, 2
• Avoid excessive platelet count elevation (keep <400 × 10⁹/L) 1, 2

Administration Requirements

Eltrombopag Administration

• Take on empty stomach OR with meal containing ≤50 mg calcium 2
• Separate from polyvalent cations by at least 2 hours before or 4 hours after 2
• Avoid concurrent administration with antacids, calcium-rich foods, dairy products, and mineral supplements 2
• This separation is critical as polyvalent cations significantly reduce eltrombopag absorption 2

Romiplostim Administration

• Administer as subcutaneous injection once weekly 1
• Reconstitute lyophilized powder per manufacturer instructions 1
• Rotate injection sites 1

Treatment Positioning and Selection

When to Use TPO-Receptor Agonists

• Use in patients with ITP lasting ≥3 months who are corticosteroid-dependent or have insufficient response to corticosteroids 7, 8
• Do not delay switching from corticosteroids beyond 6-8 weeks if requiring on-demand corticosteroid administration 7
• TPO-RAs are increasingly preferred over splenectomy due to lower risk profile 7

Choosing Between Romiplostim and Eltrombopag

• No preferential recommendation between the two agents—choice depends primarily on patient preference for route of administration (weekly subcutaneous injection vs. daily oral medication) 7, 8
• Both demonstrate similar efficacy (70-80% response rates) and safety profiles 5, 7, 8
• Switching between TPO-RAs is effective if one agent fails or causes adverse effects 9
• 80% response rate to eltrombopag after romiplostim failure, with 67% complete responses 9

Common Pitfalls and Caveats

Critical Warnings

• Eltrombopag carries boxed warning for hepatotoxicity—monitor liver function closely and discontinue if significant elevation occurs 2
• Do not use TPO-RAs to normalize platelet counts—target is ≥50 × 10⁹/L to reduce bleeding risk 1, 2
• Eltrombopag is NOT substitutable with other eltrombopag products on milligram-per-milligram basis 2

Practical Considerations

• Patients with shorter ITP duration respond better to eltrombopag 6
• Heavily pretreated or longer-duration ITP cases may require higher doses or longer treatment duration 6
• 38.9% of patients show hepatobiliary laboratory anomalies during eltrombopag treatment 6
• TPO-RAs are maintenance therapy—most patients require continuous treatment 5
• Consider concomitant rituximab in acute/persistent ITP to potentially achieve treatment-free remission 3

Monitoring for Treatment Failure

• If severe thrombocytopenia develops during treatment, assess for neutralizing antibodies 1
• If maximum dose reached without adequate response, consider switching to alternative TPO-RA 9
• Response to second TPO-RA is related to reason for discontinuing first agent 9