Lusutrombopag

Indications

Lusutrombopag is used for: Thrombocytopenia

Adult Dose

Thrombocytopenia Indicated for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure Begin dosing 8-14 days prior to scheduled procedure Patients should undergo their procedure 2-8 days after the last dose Recommended dose: 3 mg PO qDay for 7 days Hepatic impairment Mild-to-moderate (Child-Pugh A or B): No clinically meaningful effects on the pharmacokinetics Severe (Child-Pugh C): Mean observed peak plasma concentration and AUC decreased by 20-30% in patients (compared with patients with Child-Pugh A and B); however, ranges for peak plasma concentration and AUC overlapped among patients with Child-Pugh class A, B, and C liver disease

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl 30-90 mL/min): No clinically meaningful effects on the pharmacokinetics Severe (CrCl <30 mL/min) or hemodialysis: Limited data

Administration

Contra Indications

Precautions

Thrombotic or thromboembolic complications Thrombopoietin (TPO) receptor agonists, such as lusutrombopag, have been associated with thrombotic and thromboembolic complications (eg, portal vein thrombosis) in patients with chronic liver disease Consider the potential increased thrombotic risk when administering drug to patients with known risk factors for thromboembolism (eg, genetic prothrombotic conditions [factor V Leiden, prothrombin 20210A, antithrombin deficiency, or protein C or S deficiency]) In patients with ongoing or prior thrombosis or absence of hepatopetal blood flow, use lusutrombopag if the potential benefit justifies the potential risk Should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts

Pregnancy-Lactation

Pregnancy There are no available data on use in pregnant women to inform a drug-associated risk Animal data In animal reproduction studies, oral administration of lusutrombopag to pregnant rats during organogenesis and the lactation period resulted in adverse developmental outcomes These finding were observed at exposures based on AUC that were substantially higher than the AUC observed in patients (~89 times) at the recommended clinical dose of 3 mg qDay; advise pregnant women of the potential risk to a fetus Lactation There is no information on the presence of lusutrombopag in human milk, the effects on the breastfed child, and the effects on milk production Drug was present in the milk of lactating rats Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition Clinical considerations Lactating women should interrupt breastfeeding and pump and discard breast milk during treatment and for 28 days after the last dose in order to minimize exposure to a breastfed child

Interactions

Adverse Effects

Side effects of Lusutrombopag : 1-10% Headache (5%) Portal vein thrombosis (1%)

Mechanism of Action

Thrombopoietin (TPO) receptor agonist Orally bioavailable, small molecule that interacts with the transmembrane domain of human TPO receptors expressed on megakaryocytes to induce the proliferation and differentiation of megakaryocytic progenitor cells from hematopoietic stem cells and megakaryocyte maturation