Thrombocytopenia in Chronic Liver Disease (CLD): Treatment of low platelet count in adult patients with chronic liver disease who are scheduled to undergo a medical or surgical procedure.

Thrombocytopenia in Chronic Immune Thrombocytopenia (ITP): Treatment of adult patients with chronic immune thrombocytopenia who have not responded adequately to prior therapies.

Mechanism of Action: Avatrombopag is an orally active, small-molecule thrombopoietin (TPO) receptor agonist. It stimulates the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, leading to increased platelet production. It does not compete with endogenous TPO for receptor binding and works additively with TPO to enhance platelet formation.

Pharmacodynamics – Platelet Response: Avatrombopag produces dose-dependent and exposure-dependent increases in platelet count in adults. Platelet elevation typically begins within 3 to 5 days after initiating a 5-day treatment course, with peak levels reached between 10 to 13 days. Platelet counts then gradually decline, returning close to baseline within approximately 35 days.

Pharmacodynamics – Cardiac Electrophysiology: At therapeutic doses (40 mg and 60 mg), avatrombopag does not cause clinically significant prolongation of the QT interval. Based on clinical trial data, QTc prolongation greater than 20 ms is not expected at recommended doses.

Recommended Dosage for Patients with Chronic Liver Disease: Recommended Dose and Duration in Patients with Chronic Liver Disease Scheduled to Undergo a Procedure

• Platelet count less than 40X10 /L: 60 mg (3 tablets) for 5 days
• Platelet count 40 to less than 50X10 /L: 40 mg (2 tablets) for 5 days

Recommended Dosage for Patients with Chronic Immune Thrombocytopenia: Initial Dose Regimen: Begin Avatrombopag at a starting dose of 20mg (1tablet) once daily with food.

Avatrombopag Dose Adjustments for Patients with Chronic Immune ThrombocytopeniaLess than 50 after at least 2 weeks of Avatrombopag x 10 /L: Increase One Dose Level. Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.

Between 200 and 400 x 10 /L: Decrease One Dose Level. Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.

Greater than 400 x 10 /L: Stop Avatrombopag. Increase platelet monitoring to twice weekly. When platelet count is less than 150 x10 9 /L, decrease One Dose Level per Table 3 and reinitiate therapy.

Less than 50 after 4 weeks of Avatrombopag 40 mg once daily x 10 /L: Discontinue Avatrombopag.

Greater than 400 after 2 weeks of Avatrombopag 20 mg weekly x 10 /L: Discontinue Avatrombopag.

Or, as directed by the registered physician

Effect of other drugs on Avatrombopag:

Moderate or strong dual inhibitors of CYP2C9 and CYP3A4: Concomitant use may increase Avatrombopag exposure (AUC), potentially raising the risk of adverse effects. A reduced starting dose of Avatrombopag is recommended in such cases.

Moderate or strong dual inducers of CYP2C9 and CYP3A4: Co-administration may decrease Avatrombopag exposure, potentially reducing its effectiveness. An increased starting dose may be required when used with these agents.

Contraindicated in patients with known hypersensitivity to Avatrombopag or any of its components.

In chronic liver disease: Common adverse effects include fever, abdominal pain, nausea, headache, fatigue, and peripheral edema.

In chronic immune thrombocytopenia (ITP): Common adverse effects include headache, fatigue, confusion, nosebleeds, upper respiratory tract infection, joint pain, gum bleeding, petechiae, and nasopharyngitis.

Pregnancy: Animal studies suggest that Avatrombopag may cause harm to the fetus. There is insufficient data in pregnant women. Use only if the potential benefit justifies the potential risk.

Lactation: There is no information regarding its presence in human milk or its effects on the breastfed infant. Due to potential serious adverse effects, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.

Avatrombopag, as a TPO receptor agonist, may increase the risk of thrombotic and thromboembolic events. Cases of portal vein thrombosis have been reported in patients with chronic liver disease. Patients with known risk factors for thrombosis, including genetic conditions such as Factor V Leiden, Prothrombin mutation, or deficiencies of antithrombin, protein C or S, should be treated with caution. Avatrombopag should not be used solely to normalize platelet counts in patients with chronic liver disease.

• Pediatric use: Safety and effectiveness have not been established
• Geriatric use: No significant difference observed compared to younger patients

Overdose may lead to excessive elevation of platelet counts, increasing the risk of thrombotic complications. Patients should be closely monitored and treated accordingly. There is no specific antidote, and hemodialysis is unlikely to be effective due to high protein binding.

Store below 30°C, protected from light and moisture. Keep out of reach of children.