Firazyr Avatrombopag Acetate Injection

1. Indications and Usage
Thrombocytopenia in Chronic Liver Disease (CLD):
Indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
Note: Dosing is based on baseline platelet count.
Immune Thrombocytopenia (ITP):
Indicated for the treatment of previously treated chronic immune thrombocytopenia in adult patients who have an inadequate response to previous therapies.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Administration Instructions:
Can be taken with or without food (unlike Eltrombopag, it is not significantly affected by dietary calcium or polyvalent cations).
Recommended Dosage (CLD – Periprocedural):
Baseline Platelet Count < 40 × 10⁹/L: 60 mg once daily for 5 days.
Baseline Platelet Count 40–< 50 × 10⁹/L: 40 mg once daily for 5 days.
Procedure Timing: The scheduled procedure should be performed 5 to 8 days after the last dose.
Recommended Dosage (ITP – Chronic):
Starting Dose: 20 mg once daily.
Titration: Adjust dose to maintain the lowest platelet count sufficient to reduce bleeding risk.
Discontinuation: If platelet count is below normal range after 2 consecutive weeks of treatment, discontinue dosing.
3. Mechanism of Action
TPO Receptor Agonist:
Avatrombopag is an orally bioavailable small molecule that binds to the transmembrane domain of the human TPO receptor (c-Mpl).
Non-Competitive Binding:
Unlike endogenous TPO, it binds to a different site and does not compete with TPO for receptor binding.
Platelet Production:
It stimulates the proliferation and differentiation of megakaryocyte progenitor cells in the bone marrow, leading to increased platelet production.
4. Safety and Warnings
Thrombotic/Thromboembolic Complications:
Treatment may increase the risk of thrombotic/thromboembolic complications (e.g., Portal Vein Thrombosis).
Monitor for signs of thrombosis.
Discontinue Avatrombopag if platelet count exceeds the target range or rises too rapidly.
Loss of Response:
If the response is lost (i.e., platelet count does not increase despite adherence), consider the development of neutralizing antibodies.
5. Adverse Reactions
Most Common (CLD):
Headache, nausea, diarrhea, asthenia, and fever.
Most Common (ITP):
Headache, fatigue, upper abdominal pain, and nasopharyngitis.
Serious Reactions:
Portal vein thrombosis, hepatic encephalopathy.
6. Drug Interactions
CYP Enzymes:
Avatrombopag is a substrate of CYP2C9 and CYP3A4.
Inhibitors: Concomitant use with moderate/strong CYP2C9/CYP3A4 inhibitors may increase Avatrombopag exposure (reduce dose in ITP).
Inducers: Concomitant use with moderate/strong CYP2C9/CYP3A4 inducers may decrease Avatrombopag exposure (increase dose in ITP).
Note: In CLD patients, dose adjustments for drug interactions are generally not required due to the short-term treatment course.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Avatrombopag.
Appearance: Coated tablets (20 mg and 30 mg strengths).
Storage:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).