Is eltrombopag (thrombopoietin receptor agonist) safe to use during pregnancy?

Eltrombopag in Pregnancy

Eltrombopag should generally be avoided during pregnancy due to insufficient safety data, but may be considered in severe, refractory cases of thrombocytopenia when maternal benefits clearly outweigh potential fetal risks and after failure of conventional therapies.

FDA Classification and Official Guidance

The FDA classifies eltrombopag as Pregnancy Category C, indicating that animal studies have shown adverse effects and there are no adequate well-controlled studies in pregnant women 1.

• Animal studies demonstrated embryolethality and reduced fetal weights at maternally toxic doses (6 times human exposure in ITP patients) 1
• Available human data from case reports and postmarketing surveillance are insufficient to assess drug-associated risks for major birth defects, miscarriage, or adverse maternal/fetal outcomes 1
• The drug should only be used if potential benefits justify potential risks to the fetus 1

Clinical Context for Use

Eltrombopag may be considered only in refractory cases where conventional treatments have failed and severe thrombocytopenia poses immediate maternal risk 2, 3, 4.

When Conventional Therapies Fail:

• First-line treatments (corticosteroids, intravenous immunoglobulin) should be exhausted first 3
• Splenectomy, if previously performed, should have proven ineffective 2, 4
• Platelet counts should be critically low (typically <20-30 × 10⁹/L) with bleeding manifestations 3, 4

Evidence from Case Reports

The published literature includes only 6 reported cases of eltrombopag use during pregnancy, all with favorable outcomes 4:

• Successful maintenance of platelet counts between 30-90 × 10⁹/L in reported cases 2, 3, 4
• No documented teratogenic effects in the limited case series available 2, 3, 4
• Neonatal outcomes were favorable with normal platelet counts and no thrombocytosis in newborns 2, 3, 4
• One case successfully used eltrombopag starting in the first trimester (9th week) with good maternal and fetal outcomes 4

Dosing Considerations

When eltrombopag is deemed necessary:

• Start with the lowest effective dose (12.5-25 mg/day) to minimize fetal exposure 4
• Target platelet counts of 30-50 × 10⁹/L rather than normal ranges to reduce drug exposure while maintaining hemostatic safety 3
• Consider dose escalation at 34 weeks gestation in preparation for delivery to achieve counts >50 × 10⁹/L 4
• The drug was detected in offspring plasma in animal studies, indicating placental transfer 1

Monitoring Requirements

Intensive maternal and fetal surveillance is mandatory if eltrombopag is used 2:

• Weekly platelet count monitoring throughout pregnancy 3, 4
• Neonatal platelet counts should be checked on days 2 and 5 after birth to assess for thrombocytosis 2, 4
• Developmental follow-up of exposed infants is recommended given limited long-term data 4

Critical Caveats

The routine use of eltrombopag in pregnancy should be avoided due to insufficient safety data 2.

• Use should be limited to life-threatening maternal thrombocytopenia refractory to all conventional therapies 2, 3
• Informed written consent discussing unknown risks is essential before initiation 4
• The decision must weigh severe maternal bleeding risk against theoretical fetal risks 1, 2
• Alternative approaches including platelet transfusions should be considered first, despite their limitations 3

This represents an off-label use with very limited human data, and each case requires careful risk-benefit analysis prioritizing maternal survival while acknowledging unknown fetal effects 1, 2, 4.