Avatrombopag

Treatment of Thrombocytopenia in Patients with Chronic Liver Disease (CLD): It is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.

Treatment of Thrombocytopenia in Patients with Chronic Immune Thrombocytopenia (ITP): It is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a 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 an increased production of platelets. The median time to maximal concentration (Tmax) occurred at 5 to 6 hours post-dose. Avatrombopag has an estimated mean volume of distribution (%CV) of 180 L (25%). Avatrombopag is greater than 96% bound to human plasma proteins. The mean plasma elimination half-life (%CV) of avatrombopag is approximately 19 hours (19%). The mean (%CV) of the clearance of avatrombopag is estimated to be 6.9 L/hr (29%). Avatrombopag is primarily metabolized by cytochrome P450 CYP2C9 and CYP3A4. Fecal excretion accounted for 88% of the administered dose, with 34% of the dose excreted as unchanged avatrombopag. Only 6% of the administered dose was found in urine.

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 40X10⁹/L: 60 mg (3 tablets) for 5 days
• Platelet count 40 to less than 50X10⁹/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 Thrombocytopenia-

Less than 50 after at least 2 weeks of Avatrombopag x 10⁹/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 10⁹/L: Decrease One Dose Level. Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.

Greater than 400 x 10⁹/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 10⁹/L: Discontinue Avatrombopag.

Greater than 400 after 2 weeks of Avatrombopag 20 mg weekly x 10⁹/L: Discontinue Avatrombopag.

Or, as directed by the registered physician.

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 40X10⁹/L: 60 mg (3 tablets) for 5 days
• Platelet count 40 to less than 50X10⁹/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 Thrombocytopenia-

Less than 50 after at least 2 weeks of Avatrombopag x 10⁹/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 10⁹/L: Decrease One Dose Level. Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.

Greater than 400 x 10⁹/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 10⁹/L: Discontinue Avatrombopag.

Greater than 400 after 2 weeks of Avatrombopag 20 mg weekly x 10⁹/L: Discontinue Avatrombopag.

Or, as directed by the registered physician.

In patients starting moderate or strong dual inhibitors of CYP2C9 and CYP3A4 while receiving Avatrombopag, monitor platelet counts and adjust Avatrombopag dose as necessary.

It is contraindicated in patients with hypersensitivity to Avatrombopag or any component of this product.

In patients with chronic liver disease, the most common adverse reactions were pyrexia, abdominal pain, nausea, headache, fatigue, and edema peripheral. In patients with chronic immune thrombocytopenia, the most common adverse reactions were headache, fatigue, confusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae and nasopharyngitis.

Pregnant women should be advised of the potential risk to a fetus. Females of reproductive potential should be advised to inform their prescriber of a known or suspected pregnancy. Women should be advised not to breastfeed during treatment with Avatrombopag and for at least 2 weeks after the final dose.

Thrombotic/Thromboembolic Complications : Avatrombopag is a thrombopoietin (TPO) receptor agonist and
TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease or chronic immune thrombocytopenia. Monitor platelet counts and for thromboembolic events and institute treatment promptly.