PROMACTA KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMACTA KIT (PROMACTA KIT).
Thrombopoietin receptor agonist; binds to and activates the thrombopoietin receptor (c-Mpl), leading to increased platelet production.
| Metabolism | Primarily metabolized via CYP1A2, CYP2C8, and UDP-glucuronosyltransferases (UGT1A1, UGT1A3); also metabolized via oxidative cleavage. |
| Excretion | Fecal (59% unchanged, 20% as metabolites); renal (31%, <1% unchanged) |
| Half-life | 21-35 hours in ITP patients; 26-35 hours in healthy subjects |
| Protein binding | ≥99% bound to albumin |
| Volume of Distribution | Vd/F 6.2 L/kg; extensive tissue distribution |
| Bioavailability | Oral: 72% (relative to oral solution under fed conditions) |
| Onset of Action | Oral: 7-14 days to achieve platelet count ≥50,000/μL |
| Duration of Action | Platelet count declines to baseline within 2 weeks after discontinuation |
Eltrombopag 50 mg orally once daily, with or without food; for ITP or SAA, if no response after 2 weeks, increase to 75 mg once daily (max 75 mg/day). Take on empty stomach (at least 1 hour before or 2 hours after meals) and at least 4 hours after calcium-rich foods, antacids, or multivitamins.
| Dosage form | FOR SUSPENSION |
| Renal impairment | For GFR < 60 mL/min: Starting dose 50 mg once daily; monitor closely. For GFR < 50 mL/min: Reduce dose to 25 mg once daily; increase based on response to max 75 mg/day. No data for ESRD on dialysis; use with caution. |
| Liver impairment | For Child-Pugh Class A: Starting dose 25 mg once daily. For Child-Pugh Class B or C: Avoid use (risk of hepatotoxicity). For moderate to severe hepatic impairment (Child-Pugh >5): Not recommended. |
| Pediatric use | For ITP in patients ≥1 year: Starting dose 25 mg once daily for patients 1-5 years (12.5 mg if <12 kg); for patients ≥6 years: 50 mg once daily. Increase to 75 mg once daily if no response after 2 weeks (max 75 mg/day). For SAA in patients ≥2 years: Same dosing as adults (50 mg once daily, increase to 75 mg if needed). Weight-based: <12 kg: 12.5 mg/day; 12-21 kg: 25 mg/day; ≥21 kg: 50 mg/day. |
| Geriatric use | No specific dose adjustments recommended for elderly based on age alone. Monitor renal and hepatic function closely due to age-related decline; consider starting at lower end of dosing range (25-50 mg once daily) if multiple comorbidities or impaired organ function. No significant differences in efficacy or safety observed in studies. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMACTA KIT (PROMACTA KIT).
| Breastfeeding | Eltrombopag is excreted in human milk at low levels (M/P ratio approximately 0.1). Due to limited data, potential for thrombocytosis in the infant exists, and serious adverse reactions (e.g., thrombosis) cannot be excluded. Caution is advised; consider discontinuing breastfeeding or the drug based on importance to mother. |
| Teratogenic Risk | PROMACTA (eltrombopag) is Pregnancy Category C. Animal studies have shown embryofetal toxicity including reduced fetal weights and increased incidences of fetal abnormalities (e.g., omphalocele, skull malformations) at doses 1.2 times the human exposure based on AUC. In the first trimester, there is an increased risk of major congenital malformations; in the second and third trimesters, exposure may cause fetal thrombocytopenia and potential bleeding. Use only if maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
Risk for hepatotoxicity: Monitor liver function before and during treatment; discontinue if clinically significant liver injury occurs.
| Serious Effects |
Hypersensitivity to PROMACTA or any component of the formulation; acute or chronic liver disease (not specified as absolute but caution advised).
| Precautions | Hepatotoxicity, bone marrow reticulin formation (risk of cytopenias), thrombotic/thromboembolic complications (especially in patients with hepatic impairment), risk of progression to acute myeloid leukemia or myelodysplastic syndromes in SAA patients, rebound thrombocytopenia after discontinuation, interference with platelet function tests (use citrate-based assays). |
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| Fetal Monitoring | Monitor complete blood counts with platelet counts weekly for the first month, then monthly throughout pregnancy. Monitor liver function tests monthly due to risk of hepatotoxicity. Additionally, monitor for signs of thrombosis (e.g., DVT, pulmonary embolism) and fetal growth via ultrasound if prolonged use. |
| Fertility Effects | Eltrombopag did not impair fertility in animal studies at doses 2.5 times the human exposure. No human data on fertility effects. Use in women of childbearing potential should be accompanied by a negative pregnancy test and contraception advice. |