ELTROMBOPAG OLAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELTROMBOPAG OLAMINE (ELTROMBOPAG OLAMINE).
Thrombopoietin receptor agonist that binds to and activates the thrombopoietin receptor (c-Mpl), leading to increased proliferation and differentiation of megakaryocytes and subsequent platelet production.
| Metabolism | Primarily metabolized via cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. Involves CYP1A2 and CYP2C8, with UGT1A1 and UGT1A3 contributing to glucuronidation. Also metabolized by CYP2C9 and CYP2C19 to a lesser extent. |
| Excretion | Primarily fecal (59%) and renal (31%), with unchanged drug representing <1% in urine and ~20% in feces; biliary elimination accounts for most of the fecal route. |
| Half-life | Terminal elimination half-life is approximately 21–32 hours (mean ~29 hours) in healthy subjects. At steady state, clinically relevant due to once-daily dosing with delayed platelet response. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.76 L/kg (mean 57 L in a 75 kg adult), indicating distribution beyond plasma into extravascular tissues. |
| Bioavailability | Oral bioavailability is approximately 59% (range 52–72%) under fed conditions; administration with food increases AUC by 43% and Cmax by 65% compared to fasting. |
| Onset of Action | Oral: Clinical effect (platelet count increase) observed within 1–2 weeks; peak response by 2–3 weeks. No IV route. |
| Duration of Action | Platelet count returns to baseline within 1–2 weeks after discontinuation; duration of effect is sustained with continued dosing. |
50 mg orally once daily; for patients of East Asian ancestry with ITP, start at 25 mg orally once daily. Dose adjustments based on platelet counts: increase up to 75 mg daily or decrease to 25 mg daily as needed.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution and monitor serum creatinine; specific dose recommendations not established. |
| Liver impairment | Child-Pugh Class A: no dose adjustment. Child-Pugh Class B: initial dose 25 mg once daily. Child-Pugh Class C: initial dose 12.5 mg once daily. Titrate based on platelet response. |
| Pediatric use | For pediatric patients 1 year and older with ITP: 50 mg orally once daily for those <12 years old; for patients ≥12 years, same as adult dosing. For patients of East Asian ancestry, start at 25 mg once daily. Dose titration based on platelet counts; maximum 75 mg once daily. |
| Geriatric use | No specific dose adjustments based on age alone, but caution due to higher risk of thrombosis, hepatic impairment, and renal dysfunction. Start at lowest recommended dose and titrate based on platelet response and tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELTROMBOPAG OLAMINE (ELTROMBOPAG OLAMINE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for thrombocytosis and adverse effects in the infant, breastfeeding is not recommended during treatment and for at least 2 weeks after last dose. |
| Teratogenic Risk | Animal studies have shown embryofetal toxicity (reduced fetal weight, increased resorptions, and skeletal variations) at exposures similar to human therapeutic doses. There are no adequate human studies. Use only if benefit outweighs risk. In first trimester, avoid due to potential teratogenicity; in second and third trimesters, risk may be lower but data are insufficient. Thrombopoietin receptors are expressed on placental tissue, and theoretical risk of thrombocytosis-related placental thromboembolism exists. |
■ FDA Black Box Warning
Risk of hepatotoxicity: Eltrombopag may cause severe and potentially life-threatening hepatotoxicity. Monitor liver function tests before and during therapy. Discontinue if clinically significant hepatotoxicity occurs or if ALT levels increase to >=3x ULN and are progressive or persistent.
| Serious Effects |
["Hypersensitivity to eltrombopag or any component of the formulation","Concurrent use with anticoagulants may increase bleeding risk? (Note: Not absolute contraindication but caution; per FDA labeling, none specified as absolute contraindication beyond hypersensitivity)"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests prior to initiation and every 2 weeks during dose titration, then monthly. Discontinue if clinically significant hepatotoxicity occurs.","Thrombotic/thromboembolic complications: Increased risk of thrombosis. Use with caution in patients with known risk factors for thromboembolism.","Risk of bone marrow reticulin formation and bone marrow fibrosis: Monitor peripheral blood for cytopenias; consider bone marrow biopsy if new or worsening morphological abnormalities or cytopenias occur.","Cataracts: Reported in clinical trials. Perform baseline and periodic eye examinations.","Interactions with polyvalent cations: Cations (e.g., calcium, iron, magnesium, zinc) chelate eltrombopag; administer at least 4 hours before or after products containing these cations."] |
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| Fetal Monitoring | Monitor maternal platelet count weekly during pregnancy, adjust dose to maintain platelets within target range (typically 50-200 x 10^9/L). Assess for signs of thromboembolic events (pulmonary embolism, deep vein thrombosis) due to thrombocytosis risk. Monitor liver function tests (ALT, AST, bilirubin) monthly due to risk of hepatotoxicity. Fetal ultrasound for growth and anatomy if exposure occurs in first trimester. |
| Fertility Effects | No human data on fertility. Animal studies showed no adverse effects on male or female fertility at exposures up to 7 times the human AUC. Theoretical risk of hormonal disruption due to thrombopoietin receptor expression on reproductive tissues; however, no significant impact is expected at therapeutic doses. |