Avatrombopag — Drug Monograph

Brand names: Doptelet

Drug class: Supportive Care Agent

Mechanism of Action

Orally bioavailable, small-molecule thrombopoietin receptor (TPO-R / c-Mpl) agonist. Binds the transmembrane domain of the TPO receptor at a site distinct from endogenous thrombopoietin (non-competitive), triggering JAK2/STAT5 signaling that drives proliferation and differentiation of megakaryocytes and their bone-marrow progenitors, increasing platelet production. Unlike eltrombopag, avatrombopag does not chelate polyvalent cations and has no food-interaction or hepatotoxicity restrictions — it must, in fact, be taken WITH food to optimize absorption.

FDA Indications

• Thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure (FDA approved 2018)
• Chronic immune thrombocytopenia (ITP) in adults with insufficient response to a prior therapy (FDA approved 2019)

Common Side Effects

• Headache
• Fatigue
• Peripheral edema
• Nausea
• Contusion / bruising
• Petechiae
• Nasopharyngitis / upper respiratory infection

Clinical Pearl

Avatrombopag was developed specifically to overcome eltrombopag's two biggest practical limitations: the strict cation-free fasting window and the hepatotoxicity/boxed-warning history. It has no food restriction (indeed requires food), no chelation interactions, and no REMS. In persistent chemotherapy-induced thrombocytopenia — a common cause of dose reductions and delays in GI oncology — TPO-RAs such as avatrombopag are being studied (e.g. the phase II ACT-GI trial) to keep patients on…

Related Therapies & Mechanisms

• Defibrotide (Defitelio) — Supportive Care Agent · Supportive Care
• Dexrazoxane (Zinecard) — Supportive Care Agent · Supportive Care
• Eltrombopag (Promacta) — Supportive Care Agent · Supportive Care
• Fostamatinib (Tavalisse) — Supportive Care Agent · Supportive Care