ELTROMBOPAG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELTROMBOPAG (ELTROMBOPAG).
Eltrombopag is a small-molecule agonist of the thrombopoietin (TPO) receptor, activating the JAK/STAT signaling pathway to stimulate megakaryocyte proliferation and differentiation, thereby increasing platelet production.
| Metabolism | Primarily metabolized via CYP1A2 and CYP2C8; minor contribution from UGT1A1 and UGT1A3. Undergoes oxidative metabolism and glucuronidation. |
| Excretion | Fecal (≥59% as unchanged drug, ~31% as metabolites); renal (~20% as metabolites, <1% as unchanged drug). Total excretion: feces ~88%, urine ~13%. |
| Half-life | ~21–32 hours in healthy subjects; 26–35 hours in ITP patients. Supports once-daily dosing. |
| Protein binding | >99.9% bound to plasma proteins (albumin and others). |
| Volume of Distribution | ~6.4 L (approx 0.1 L/kg) – small, consistent with extensive plasma protein binding and limited tissue distribution. |
| Bioavailability | ~52% (oral, fed state). Food (high-fat meal) reduces Cmax and AUC by ~70% and ~50%, respectively; take on empty stomach. |
| Onset of Action | 1–2 weeks (oral); reduction in bleeding and rise in platelet count typically observed after 1–2 weeks of daily dosing. |
| Duration of Action | Platelet counts persist until drug is eliminated; twice-weekly dosing may maintain effect. Effect wanes within 1–2 weeks of discontinuation. |
50 mg orally once daily; adjust dose based on platelet response. Maximum dose 75 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: initial dose 25 mg once daily. Child-Pugh Class C: avoid use. |
| Pediatric use | Age 1 year and older: 25 mg to 75 mg orally once daily based on body weight: ≥12 kg: 25 mg; 12–27 kg: 25 mg; >27 kg: 50 mg. Adjust per platelet response. Not approved for children <1 year. |
| Geriatric use | No specific dose adjustment recommended in elderly; monitor platelet counts closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELTROMBOPAG (ELTROMBOPAG).
| Breastfeeding | Eltrombopag is excreted in rat milk. It is not known whether eltrombopag is excreted in human milk. The M/P ratio is not available. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Based on animal studies, eltrombopag is embryotoxic and teratogenic in rats and rabbits at doses 0.3-3 times the human clinical exposure based on AUC. In pregnant rats, fetal malformations (including eye, skull, and skeletal abnormalities) were observed. In rabbits, fetal resorptions and decreased fetal body weight occurred. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
Risk of hepatotoxicity: Severe and potentially fatal liver injury may occur. Monitor liver function tests (ALT, AST, bilirubin) prior to initiation, every 2 weeks during dose adjustment, and monthly thereafter.
| Serious Effects |
None known.
| Precautions | ["Hepatotoxicity: Monitor liver enzymes; discontinue if clinically significant elevations occur.","Risk for thrombotic/thromboembolic complications, including portal vein thrombosis, particularly in chronic liver disease patients.","Cataracts: Perform baseline ocular exam and monitor during therapy.","Bone marrow fibrosis: Monitor peripheral blood smears for morphological abnormalities.","Interference with bilirubin and uric acid assays: Use alternative test methods."] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelet counts regularly. Monitor liver function tests (ALT, AST, bilirubin) monthly during treatment. In pregnant women, additional monitoring for fetal growth and development via ultrasound may be warranted given animal data. Monitor for signs of bleeding or thrombosis. |
| Fertility Effects | Animal studies in rats showed no adverse effects on male or female fertility at exposures up to 2.3 times the human clinical exposure based on AUC. However, eltrombopag altered estrous cycling in female rats at higher doses. Effects on human fertility are unknown. |