PROMACTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMACTA (PROMACTA).
Thrombopoietin receptor agonist. Binds to and activates the thrombopoietin receptor (c-Mpl) on hematopoietic stem cells, megakaryocyte progenitors, and megakaryocytes, leading to increased platelet production.
| Metabolism | Primarily metabolized by CYP1A2, CYP2C8, and UGT1A1; also a substrate of UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7. |
| Excretion | Primarily fecal (93%) with minimal renal excretion (<6%). Biliary excretion of unchanged drug and metabolites contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 21–32 hours in healthy subjects; in ITP patients, half-life ranges 26–35 hours supporting once-daily dosing. |
| Protein binding | Highly protein bound (>99%) primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution is about 0.62 L/kg (based on population PK), indicating distribution into total body water with some tissue binding. |
| Bioavailability | Oral bioavailability is approximately 50% (range 30–70%) with moderate food effect (AUC reduced by ~25% with high-fat meal). |
| Onset of Action | Oral: Platelet count increases observed within 1–2 weeks of daily dosing; peak effect reached by 2–3 weeks. |
| Duration of Action | Sustained platelet elevation persists with continued daily dosing; upon discontinuation, platelet counts return to baseline within 1–2 weeks. |
50 mg orally once daily; increase to 75 mg once daily if platelet count remains <50,000/µL after 2 weeks; maximum 75 mg/day
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min) or dialysis; use with caution. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment; moderate to severe (Child-Pugh B or C): starting dose 25 mg once daily, with careful monitoring; maximum 50 mg once daily. |
| Pediatric use | 1 year and older: starting dose 25 mg orally once daily; for children 6 to 11 years, increase to 37.5 mg once daily if inadequate response; for 12 years and older, increase to 50 mg once daily if needed; maximum 75 mg/day. Weight-based: not recommended, use fixed doses per age group. |
| Geriatric use | No specific dose adjustment recommended; however, elderly patients may have increased risk of adverse effects (e.g., hepatotoxicity, thromboembolic events); use lowest effective dose and monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMACTA (PROMACTA).
| Breastfeeding | It is not known whether eltrombopag is excreted in human milk. In animal studies, eltrombopag was excreted in rat milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio: not determined in humans. |
| Teratogenic Risk | PROMACTA (eltrombopag) is Pregnancy Category C. In animal studies, eltrombopag was teratogenic at maternally toxic doses, causing delayed skeletal ossification, reduced fetal weight, and increased resorptions. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit justifies potential risk to the fetus. First trimester: unknown risk; avoid unless necessary. Second and third trimesters: limited data; consider maternal benefit vs fetal risk. |
■ FDA Black Box Warning
Risk of hepatotoxicity. Monitor liver function tests (LFTs) before and during treatment. Discontinue if LFTs exceed 3 times the upper limit of normal and are progressive or accompanied by symptoms of liver injury.
| Serious Effects |
["History of hypersensitivity to eltrombopag or any component of the formulation."]
| Precautions | ["Hepatotoxicity: Monitor LFTs monthly during treatment; dose adjustment or discontinuation required for significant elevations.","Thrombotic/thromboembolic complications: Increased risk of portal vein thrombosis in patients with chronic liver disease; use with caution in patients with risk factors for thrombosis.","Risk of progression of myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML): Not indicated for treatment of thrombocytopenia due to MDS; preclinical data suggest potential stimulation of MDS clone.","Cataracts: Observed in animal studies; perform baseline and periodic ocular examinations.","Bone marrow fibrosis: Reversible increases in reticulin may occur; monitor with bone marrow biopsies if clinically indicated.","Laboratory monitoring: Monitor platelet counts weekly until stable, then monthly; adjust dose to maintain platelet count <200 x 10^9/L."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal complete blood counts (CBC) with differential and platelet counts weekly until stable, then monthly; hepatic function tests (ALT, AST, bilirubin) every 2 weeks during dose adjustment then monthly; monitor for hepatotoxicity, thromboembolic events, and cataracts. Fetal monitoring: consider fetal ultrasound if exposure occurs during pregnancy. |
| Fertility Effects | There are no clinical data on the effects of eltrombopag on human fertility. In animal studies, no adverse effects on male or female fertility were observed at exposures up to 3 times the human exposure (AUC) at 75 mg/day. |