MULPLETA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MULPLETA (MULPLETA).
MULPLETA (lusutrombopag) is a thrombopoietin receptor agonist that binds to and activates the human thrombopoietin receptor, leading to proliferation and differentiation of megakaryocytes from hematopoietic stem cells and increased platelet production.
| Metabolism | Metabolized primarily by CYP4F2 and to a lesser extent by CYP2C8 and UGT1A1. |
| Excretion | Biliary/fecal (unchanged drug and metabolites) ~93%; renal excretion ~3.9% (mostly metabolites). |
| Half-life | Terminal elimination half-life approximately 12-13 hours in healthy subjects and 20-23 hours in patients with chronic liver disease. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd/F) is about 56 L (0.7-0.8 L/kg), suggesting extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 51% under fed conditions; bioavailability is enhanced (up to 1.6-fold) when taken with a high-fat meal. |
| Onset of Action | Oral: Onset of action occurs within 2 to 6 hours after a single dose, with peak effect on platelet count typically seen within 7 to 12 days of daily dosing. |
| Duration of Action | Duration of action persists for the dosing interval (once daily); platelet counts return to baseline within approximately 2 weeks after discontinuation. |
20 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). For severe renal impairment (GFR <30 mL/min) or dialysis, reduce dose to 10 mg once daily. |
| Liver impairment | Child-Pugh A: 20 mg once daily. Child-Pugh B: reduce dose to 10 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no dose recommendations available. |
| Geriatric use | No specific dose adjustment required; use caution due to potential increased sensitivity and renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MULPLETA (MULPLETA).
| Breastfeeding | There are no data on the presence of lusutrombopag in human milk, effects on the breastfed infant, or effects on milk production. The M/P ratio is unknown. Since many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, advise women that breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | MULPLETA (lusutrombopag) is a thrombopoietin receptor agonist. Data in pregnant women are insufficient to determine drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, oral administration of lusutrombopag to pregnant rats and rabbits during organogenesis produced no evidence of teratogenicity at exposures up to 18 and 2 times the human area under the curve (AUC) at the clinical dose, respectively. However, in rats, maternal toxicity and reduced fetal weights were observed at high doses. The fetal risk cannot be excluded. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
Risk of thrombotic/thromboembolic complications: Lusutrombopag may increase the risk of thrombotic events including portal vein thrombosis. Use with caution in patients with known risk factors for thromboembolism.
| Serious Effects |
["None known"]
| Precautions | ["Thrombotic/thromboembolic events: Monitor for signs and symptoms of thrombosis, especially portal vein thrombosis.","Do not use to normalize platelet counts in patients with chronic liver disease. Use only to increase platelet counts for procedures.","Consider the risk of bleeding if platelet counts exceed normal range.","Potential for drug interactions with CYP4F2 inducers (e.g., rifampin) and inhibitors (e.g., fluconazole)."] |
Loading safety data…
| Fetal Monitoring | Monitor complete blood counts (CBC) including platelet count prior to initiation and regularly during therapy to assess response and detect thrombocytopenia after discontinuation. Monitor for signs and symptoms of thromboembolic events. No specific maternal-fetal monitoring beyond standard prenatal care is required. |
| Fertility Effects | There are no human data on the effect of lusutrombopag on fertility. In animal studies, no adverse effects on male or female fertility were observed in rats at exposures up to 18 times the human AUC at the clinical dose. |