Avatrombopag

Indications

Avatrombopag is used for: Thrombocytopenia

Adult Dose

Thrombocytopenia Patients with chronic liver disease Indicated for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure Taken orally once daily for 5 consecutive days with food Initiate dosing 10-13 days prior to the scheduled procedure Patients should undergo their procedure 5-8 days after the last dose Dose based on preprocedure platelet count Platelet count <40 x10^9/L: 60 mg PO qDay x 5 days Platelet count 40 to <50 x10^9/L: 40 mg PO qDay x 5 days Patients with chronic immune thrombocytopenia Indicated for thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment Use lowest dose needed to achieve and maintain a platelet count ?50 x10^9/L as necessary to reduce the risk for bleeding Initial dose: 20 mg PO qDay Dose adjustments by platelet count for chronic ITP Platelet count <50 x10^9/L after ?2 weeks: Increase by 1 dose level; wait 2 wk to assess effects before further adjustment Platelet count 200-400 x10^9/L: Decrease 1 dose level; wait 2 wk to assess effects before further adjustment Platelet count >400 x10^9/L: Stop avatrombopag and increase platelet monitoring to twice weekly; may reinitiated by decreasing 1 dose level when platelets <150 x10^9/L Platelet count <50 x10^9/L after 4 weeks at 40 mg/day: Discontinue avatrombopag Platelet count >400 x10^9/L after 2 weeks at 20 mg/week: Discontinue avatrombopag Dose levels for titration in ITP Dose level 6: 40 mg/day Dose level 5: 40 mg 3x/week AND 20 mg on the 4 remaining days each week Dose level 4: 20 mg/day Dose level 3: 20 mg 3x/week Dose level 2: 20 mg 2x/week OR 40 mg qWeek Dose level 1: 20 mg qWeek Hepatic impairment Child-Turcotte-Pugh grades A, B, or C or MELD score 4-23: No clinically meaningful effects on the pharmacokinetics

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl ?30 mL/min): No dose adjustment required; minimally excreted by the kidneys Severe (CrCl <30 mL/min) or hemodialysis: Unknown

Administration

Take with food

Contra Indications

Precautions

Thrombotic/thromboembolic complications Thrombopoietin (TPO) receptor agonists associated with thrombotic and thromboembolic complications in patients with chronic liver disease or chronic ITP Portal vein thrombosis reported with chronic liver disease in patients treated with thrombopoietin (TPO) receptor agonists (ADAPT-1 and ADAPT-2 clinical trials) Consider the potential increased thrombotic risk when administering to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (eg, factor V Leiden, prothrombin 20210A, antithrombin deficiency, or protein C or S deficiency) Not to be administered to patients with chronic liver disease or chronic immune thrombocytopenia in an attempt to normalize platelet counts; thromboembolic events (arterial or venous) reported Follow dosing guidelines to achieve target platelet counts; monitor patients receiving therapy for signs and symptoms of thromboembolic events and institute treatment promptly

Pregnancy-Lactation

Pregnancy Based on findings from animal reproduction studies, may cause fetal harm when administered to pregnant women In animal reproduction studies, administration resulted in adverse developmental outcomes when administered during organogenesis in rabbits and during organogenesis and the lactation period in rats However, these findings were observed at exposures based on AUC substantially higher than the AUC observed in patients at the recommended dose of 60 mg once daily Advise pregnant women of the potential risk to a fetus Lactation No data are available regarding the presence of the drug in human milk, the effects on the breastfed child, or the effects on milk production In studies, avatrombopag was present in the milk of lactating rats; when a drug is present in animal milk, it is likely the drug will be present in human milk Owing to the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose

Interactions

Adverse Effects

Side effects of Avatrombopag : >10% Pyrexia (8-11%) 1-10% Abdominal pain (6-7%) Nausea (6-7%) Headache (4-7%) Fatigue (3-4%) Peripheral edema (3-4%) <1% Hyponatremia (0.7%)

Mechanism of Action

Second-generation orally administered thrombopoietin receptor agonist (TPO-RA) Stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in an increased production of platelets Does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production