Avatech 20

• Thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure
• Thrombocytopenia in patients with chronic immune thrombocytopenia who have had insufficient response to previous treatment

Avatrombopag is an orally bioavailable, small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in increased platelet production. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production.

Avatrombopag results in dose- and exposure-dependent elevations in platelet counts. Platelet count increase is observed within 3-5 days of starting a 5-day course, with peak effect at 10-13 days. Platelet counts return to near baseline after 35 days.

Chronic Liver Disease (CLD) - Pre-procedure:

• Platelet count <40 × 10⁹/L: 60 mg (3 tablets) once daily for 5 days with food
• Platelet count 40 to <50 × 10⁹/L: 40 mg (2 tablets) once daily for 5 days with food
• Initiate dosing 10-13 days prior to procedure; perform procedure 5-8 days after last dose

Chronic Immune Thrombocytopenia (ITP):

• Initial dose: 20 mg (1 tablet) once daily with food
• Dose level adjustments (based on platelet count):
  • <50 × 10⁹/L after ≥2 weeks: Increase 1 dose level
  • 200-400 × 10⁹/L: Decrease 1 dose level
  • >400 × 10⁹/L: Stop Avatrombopag; monitor twice weekly

ITP Dose Levels: Level 6: 40 mg/day; Level 5: 40 mg 3x/week + 20 mg remaining 4 days; Level 4: 20 mg/day; Level 3: 20 mg 3x/week; Level 2: 20 mg 2x/week OR 40 mg weekly; Level 1: 20 mg weekly

Chronic Liver Disease (CLD):

• Pyrexia (8-11%)
• Abdominal pain (6-7%)
• Nausea (6-7%)
• Headache (4-7%)
• Fatigue (3-4%)
• Peripheral edema (3-4%)

Chronic ITP:

• Headache, fatigue, confusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, nasopharyngitis

Rare (<1%): Hyponatremia (0.7%)

[CONSULT YOUR DOCTOR] Pregnancy Category C. Animal studies showed adverse developmental outcomes during organogenesis. Advise pregnant women of potential risk to the fetus.

Serious Precautions:

• TPO receptor agonists are associated with thrombotic and thromboembolic complications
• Portal vein thrombosis reported in patients with chronic liver disease
• Caution in patients with known risk factors for thromboembolism (Factor V Leiden, Prothrombin 20210A, Antithrombin deficiency, Protein C or S deficiency)
• Do not use in an attempt to normalize platelet counts
• Monitor for signs and symptoms of thromboembolic events
• May cause fetal harm during pregnancy
• Breastfeeding not recommended during treatment and for 2 weeks after the last dose

Overdose may cause excessive platelet count increase and thrombotic/thromboembolic complications. Monitor patient and platelet count. Treat thrombotic complications per standard of care. No specific antidote. Hemodialysis is not expected to enhance elimination (only ~6% renally excreted, highly protein-bound).

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