Side Effects of Eltrombopag
The most common side effects of eltrombopag include gastrointestinal symptoms (nausea 9%, diarrhea 9%, vomiting 6%), headache (10-22%), elevated liver enzymes (ALT/AST increased in 5%), fatigue, and upper respiratory infections, with serious but less frequent risks including hepatotoxicity (11-15%), thrombosis (2.5-6%), and cataracts (7-11%). 1
Common Adverse Reactions (≥3% incidence)
Based on FDA labeling from placebo-controlled trials in immune thrombocytopenia patients, the following adverse reactions occur more frequently with eltrombopag than placebo 1:
- Gastrointestinal: Nausea (9% vs 3% placebo), diarrhea (9% vs 7%), vomiting (6% vs <1%)
- Infections: Upper respiratory tract infection (7% vs 6%), urinary tract infection (5% vs 4%), pharyngitis (4% vs 2%)
- Musculoskeletal: Myalgia (5% vs 2%), back pain (3% vs 2%)
- Hepatic: Elevated ALT (5% vs 3%), elevated AST (4% vs 2%)
- Neurologic: Headache (10% in extension studies), paresthesia (3% vs 2%)
- Dermatologic: Rash (3% vs 2%)
- Constitutional: Fatigue (5% in extension studies)
Serious Adverse Reactions Requiring Monitoring
Hepatotoxicity (11-15% incidence)
Liver function abnormalities are the most clinically significant common adverse effect, occurring in 11% of patients in controlled trials and 15% in real-world studies. 1, 2 These are predominantly Grade 2 or less in severity, but require monitoring:
- Serum liver tests should be monitored before and during therapy 1
- Four patients (1%) discontinued treatment due to hepatobiliary abnormalities in controlled trials 1
- Most abnormalities are reversible, though some patients experience recurrent elevations upon re-exposure 1
Thrombotic/Thromboembolic Complications (2.5-6% incidence)
Thrombosis risk is a critical concern, particularly in specific populations. The American Society of Hematology guidelines note thrombosis occurred in 2.5% of ITP patients treated with TPO-RAs 3. Real-world data shows rates of 5.9-6% 2, 4:
- Portal vein thrombosis is particularly concerning in patients with chronic liver disease—seven thrombotic events (six patients) occurred in hepatitis C patients receiving 75mg daily, with five events occurring within 30 days of completing treatment at platelet counts >200 × 10⁹/L 1
- Deep vein thrombosis, cerebral infarction reported in extension studies 4
- Monitor platelet counts regularly to avoid excessive elevation 1
Cataracts (7-11% incidence)
Cataracts developed or worsened in 7% of patients in controlled trials (same as placebo) and 11% in extension studies 1. However, 72% of affected patients had preexisting risk factors including corticosteroid use 1:
- Perform baseline ocular examination prior to starting eltrombopag 1
- Regular monitoring for signs and symptoms of cataracts during therapy 1
- Cataracts were observed in rodent toxicology studies 1
Other Serious but Rare Events
- Myelofibrosis: Reported in 2 patients in extension studies 4
- Infection: 3.7% in TPO-RA treated patients per ASH guidelines 3
- Operative complications: Not applicable (surgical intervention comparison) 3
Real-World Safety Data
Long-term safety data from the EXTEND study (median treatment duration 2.37 years, up to 8.76 years) demonstrated 4:
- Rates of thromboembolic events (6%) and hepatobiliary adverse events (15%) did not increase with treatment duration past 1 year
- Only 14% of patients withdrew due to adverse events
- Important adverse events (thrombosis, hepatobiliary, bone marrow fibrosis) were infrequent
A Turkish multi-center real-world study of 285 patients found 2:
- Headache (21.6%)—most common
- Weakness (13.7%)
- Hepatotoxicity (11.8%)
- Thrombosis (5.9%)
- Higher maximum platelet counts after treatment correlated with increased side effect likelihood
Pediatric Considerations
In pediatric patients, the most commonly reported drug-related adverse effects include 5:
- Headache
- Nausea
- Hepatobiliary laboratory abnormalities
Long-term safety data in children are limited, though adult studies have not shown clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation 5.
Critical Monitoring Recommendations
Patients must be closely monitored throughout treatment as both response and side effects may be variable during follow-up, especially regarding thrombotic risk factors. 2 The need for ongoing drug exposure with TPO-RAs means cumulative risk differs from time-limited therapies like rituximab or one-time interventions like splenectomy 3.
Administration Considerations Affecting Tolerability
Eltrombopag requires specific administration guidelines that may affect patient acceptability 3:
- Daily oral medication
- Must be taken several hours removed from food and polyvalent cations (calcium, antacids, mineral supplements)
- Take at least 2 hours before or 4 hours after medications containing polyvalent cations 1
These requirements may impact feasibility and adherence compared to alternative therapies.