Avatrom 20-MG Tablet

Mechanism of Action: 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. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production.

Pharmacodynamics: Platelet Response: Avatrombopag resulted in dose- and exposure-depen- dent elevations in platelet counts in adults. The onset of the platelet count increase was observed within 3 to 5 days of the start of a 5-day treatment course, with peak effect observed after 10 to 13 days. Subsequently, platelet counts decreased gradually, returning to near baseline values after 35 days.

Pharmacodynamics: Cardiac Electrophysiology: At exposures similar to that achieved at the 40 mg and 60 mg dose, Avatrombopag did not prolong the QT interval to any clinically relevant extent. Mean QTc prolongation effects >20 ms are not anticipated with the highest recommended therapeutic dosing regimen based on analysis of data from the pooled clinical trials in patients.

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.

Effect of Other Drugs on Avatrom in Patients with Chronic Immune Thrombocytopenia.

Moderate or Strong Dual Inhibitors of CYP2C9 and CYP3A4: Concomitant use with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 increases Avatrom AUC, which may increase the risk of Avatrom toxicities. Reduce the starting dosage of Avatrom when used concomitantly with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4.

Moderate or Strong Dual Inducers of CYP2C9 and CYP3A4: Concomitant use with a moderate or strong dual inducer of CYP2C9 and CYP3A4 decreases Avatrom AUC, which may reduce Avatrom efficacy.
Increase the recommended starting dosage of Avatrom when used concomitantly with a moderate or strong dual inducer of CYP2C9 and CYP3A4.

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.

Pregnancy: Based on findings from animal reproduction studies, Avatrombopag may cause fetal harm when administered to a pregnant woman. The available data on Avatrombopag in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Advise pregnant women of the potential risk to a fetus.

Lactation: There are no information regarding the presence of Avatrombopag in human milk, the effects on the breastfed child, or the effects on milk production. Due to the potential for serious adverse reactions in a breastfed child from Avatrombopag, breastfeeding is not recommended during treatment with Avatrombopag and for at least 2 weeks after the last dose.

Thrombotic/Thromboembolic Complications: Avatrom is a thrombopoietin (TPO) receptor agonist and TPO receptor agonists have been associated with thrombotic and thromboembolic compli- cations in patients with chronic liver disease. Portal vein thrombosis has been reported in patients with chronic liver disease treated with TPO receptor agonists. In the ADAPT-1 and ADAPT-2 clinical trials, there was 1 treatment-emergent event of portal vein thrombosis in a patient (n=1/430) with chronic liver disease and thrombocytopenia treated with Avatrom. Consider the potential increased thrombotic risk when administering Avatrom to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (Factor V Leiden, Prothrombin 20210A, Antithrombin deficiency or Protein C or S deficiency). Avatrom should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Reported clinical experience has not identified differences in responses between the elderly and younger patients.

In the event of overdose, platelet count may increase excessively and result in thrombotic or thromboembolic complications. Closely monitor the patient and platelet count. Treat thrombotic complications in accordance with standard of care. No antidote for Avatrom overdose is known. Hemodialysis is not expected to enhance the elimination of Avatrom because Avatrom is only approximately 6% renally excreted and is highly bound to plasma proteins.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.