Which oral medication is used to increase platelet counts in an adult patient with immune‑mediated thrombocytopenia who has not responded adequately to first‑line steroids?

Oral Medications to Increase Platelet Counts

Eltrombopag (25–75 mg orally daily) and avatrombopag are the primary oral thrombopoietin receptor agonists used to increase platelet counts in adult patients with immune thrombocytopenia who have failed first-line corticosteroid therapy. 1, 2

First-Line Oral TPO Receptor Agonist: Eltrombopag

Eltrombopag is initiated at 25 mg orally once daily for most adult ITP patients, with dose escalation in 25 mg increments every 2 weeks until platelet counts reach ≥50 × 10⁹/L, up to a maximum of 75 mg daily. 1, 2, 3

• Response rates range from 70–81% of patients, with more than 80% achieving platelet elevation by day 15 when receiving 50–75 mg doses. 1, 2
• The medication must be taken at least 2 hours before or 4 hours after any polyvalent cations (antacids, calcium-rich foods, mineral supplements) and either without food or with a low-calcium meal (≤50 mg calcium). 3
• Platelet counts typically begin rising within 1–2 weeks of initiating therapy. 1, 2

Critical Monitoring Requirements for Eltrombopag

• Liver function test abnormalities occur in approximately 13% of patients; hepatic function must be monitored before and regularly during therapy, with discontinuation required if clinical signs of liver damage develop. 1, 2, 3
• Complete blood counts should be monitored weekly during dose titration, then monthly once stable platelet counts are achieved. 2
• Bone marrow reticulin formation has been reported in more than 10 patients; while routine bone marrow monitoring is not recommended, it should be performed if new cytopenias or peripheral smear abnormalities appear. 1, 4

Alternative Oral Immunosuppressive Agents

When TPO receptor agonists are not suitable or have failed, several oral immunosuppressive medications can increase platelet counts, though with lower response rates and longer time to effect:

Mycophenolate Mofetil

• Dosed at 1000 mg twice daily for at least 3–4 weeks, mycophenolate achieves platelet responses in up to 75% of patients, with complete response in up to 45%. 1, 2
• Time to response is 4–6 weeks, with mild and infrequent adverse effects including headache (most common and dose-limiting), backache, and gastrointestinal symptoms. 1

Dapsone

• Dosed at 75–100 mg daily, dapsone produces responses in up to 50% of patients within approximately 3 weeks. 1, 2
• Mandatory G6PD screening is required before initiation in at-risk males to prevent hemolytic anemia. 2
• Adverse effects are infrequent and include abdominal distension, anorexia, nausea, and methemoglobinuria. 1

Danazol

• Dosed at 200 mg 2–4 times daily, with highly variable response rates (10–80% across case series) and a prolonged time to response of 3–6 months. 1
• Frequent adverse effects include acne, increased facial hair, increased cholesterol, amenorrhea, and transaminitis (abnormal liver function tests in ~41% of patients). 1

Cyclosporine A

• Dosed at 5 mg/kg/day for 6 days, then 2.5–3 mg/kg/day (titrated to blood levels of 100–200 ng/mL), with high response rates (~50–80%) in small series. 1
• Time to response is 3–4 weeks, but moderate adverse effects occur in most patients including increased serum creatinine, hypertension, fatigue, paresthesias, and gingival hyperplasia. 1

Azathioprine

• Dosed at 1–2 mg/kg daily (maximum 150 mg/day), achieving responses in up to two-thirds of patients, though requiring 3–6 months of continuous therapy. 1
• Adverse effects are generally mild but include weakness, sweating, transaminase elevations, and rarely severe neutropenia with infection. 1

Common Pitfalls and Clinical Caveats

• Upon discontinuation of eltrombopag or other TPO receptor agonists, 83–90% of patients experience platelet count decline returning to baseline within 2–4 weeks; approximately 10% may transiently fall below baseline levels. 4
• Approximately 30% of patients achieve sustained treatment-free remission lasting ≥6 months after TPO-RA discontinuation, supporting consideration of gradual tapering rather than abrupt cessation. 4, 5
• Cyclophosphamide (1–2 mg/kg orally daily) achieves responses in 24–85% of patients but carries serious toxicities including alopecia, teratogenicity, infertility, hemorrhagic cystitis, and elevated risk of myelodysplastic syndrome or acute leukemia, limiting its use to refractory cases. 1
• Eltrombopag is contraindicated in myelodysplastic syndrome due to concerns about disease progression, though it is FDA-approved for severe aplastic anemia at higher doses (150–300 mg daily). 3, 6