Fostamatinib — Drug Monograph

Brand names: Tavalisse

Drug class: Supportive Care Agent

Mechanism of Action

Oral prodrug rapidly converted to its active metabolite R406, a spleen tyrosine kinase (Syk) inhibitor. In immune thrombocytopenia, Syk is a key mediator of Fcγ-receptor signaling in splenic and hepatic macrophages; inhibiting Syk reduces antibody-mediated (Fcγ-receptor–dependent) phagocytosis and destruction of antibody-coated platelets, raising the platelet count.

FDA Indications

• Chronic immune thrombocytopenia (ITP) in adults with an insufficient response to a previous treatment (FDA approved 2018)

Common Side Effects

• Diarrhea
• Hypertension
• Nausea
• Dizziness
• Elevated liver transaminases (ALT/AST)
• Respiratory infection
• Rash
• Fatigue

Clinical Pearl

Fostamatinib is the only Syk inhibitor approved for ITP, and it works upstream of platelet destruction by blunting macrophage Fcγ-receptor signaling — a mechanism complementary to the TPO receptor agonists (which instead boost production). It is a useful second-line oral option, but requires active management of its two signature toxicities: hypertension and transaminase elevation.

Related Therapies & Mechanisms

• Avatrombopag (Doptelet) — Supportive Care Agent · Supportive Care
• Defibrotide (Defitelio) — Supportive Care Agent · Supportive Care
• Dexrazoxane (Zinecard) — Supportive Care Agent · Supportive Care
• Eltrombopag (Promacta) — Supportive Care Agent · Supportive Care