Drug information of Fostamatinib
Mechanism of effect
Tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK)
Major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor; R406 reduces antibody-mediated destruction of platelets
The active metabolite of fostamatinib, R406, inhibits signal transduction by Fcγ receptors involved in the antibody-mediated destruction of platelets by immune cells in chronic ITP. This results in increased platelet counts in this population.
R406 produces inhibition of T and B lymphocyte activation by T-cell receptors (TCRs) and B-cell receptors (BCRs) respectively. It can also inhibit signalling via Fcε receptors which could have applications in treating allergic symptoms through prevention of mast cell degranulation. Inhibition of Fc receptor signalling system also affected by R406 suppresses both dendritic cell maturation and antigen presentation and may contribute to the effects of fostamatinib. As a knock-on effect of disabling signal transduction from Fc receptors, TCRs, and BCRs, the production of inflammatory mediators and cytokines like tumour necrosis factor α, leukotriene C4, interleukin-8, and granulocyte-macrophage colony-stimulating factor.
Fostamatinib can produce hypertension through off-target effects
Values are for active metabolite (R406)
Absolute bioavailability: 55%
Peak plasma concentration: 550 ng/mL
AUC: 7080 ng•hr/mL
Protein bound: 98.3%
Vd, steady-state: 256 L
Prodrug that is converted in the gut by alkaline phosphatase to the major active metabolite, R406
R406 is extensively metabolized, primarily through pathways of CYP450-mediated oxidation (by CYP3A4) and glucuronidation (by UDP glucuronosyltransferase [UGT]1A9)
Half-life: 15 hr
Excretion: 80% (feces); 20% (urine)
Immune Thrombocytopenia (ITP)
Initial dose: 100 mg PO BID
After a month, if platelet count has not increased to at least 50 x 10^9/L, increase dose to 150 mg PO BID
Use the lowest dose to achieve and maintain a platelet count at least 50 x 10^9/L as necessary to reduce the risk of bleeding
<18 years: Safety and efficacy not established
Side effectsHigh Blood Pressure , Diarrhea , nausea , chest pain , vertigo , tiredness , Abdominal pain , Rash
InteractionsDaunorubicin , Efavirenz , lumacaftor and Ivacaftor , Etravirine , Dabrafenib , Mibefradil , cobicistat , Delavirdine , Oxecarbazepin , Primidone , Rifampin , Phenobarbital , Phenytoin , Carbamazepine , Secobarbital , Apalutamide , conivaptan , nafcillin , nevirapine , mitotane , Butalbital and Acetaminophen , Fosphenytoin , Idelalisib , Butabarbital , Colchicine , Enzalutamide , Rifabutin , Rifapentine , Pentobarbital , Amobarbital , Desloratadine , trametinib , Entrectinib , oleandomycin , Gefitinib , Remdesivir , Cannabidiol , talazoparib , Fidaxomicin
Hypertension can occur, including hypertensive crisis; patients with preexisting hypertension may be more susceptible; monitor blood pressure q2Weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for control
Elevated LFTs (mainly ALT and AST) reported; transaminases typically recover to baseline levels within 2-6 weeks of dose-modification; monitor liver function tests monthly during treatment
Diarrhea commonly occurs; use supportive care measures (eg, dietary changes, hydration, and/or antidiarrheal medication) early after the onset of symptoms
Neutropenia reported, including febrile neutropenia; monitor ANC monthly and for infection during treatment
Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women
Drug interaction overview
- Effect of other drugs on fostamatinib
- Strong CYP3A4 inhibitors: Coadministration increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions; fostamatinib dose reduction may be required
- Strong CYP3A4 inducers: Coadministration not recommended owing to reduced exposure to R406
- Effect of fostamatinib on other drugs
- CYP3A4, BCRP, and/or P-gp substrates: Coadministration with fostamatinib may increase concentrations of some substrate drugs; substrate drug may require dose reduction
Points of recommendation
Read the Patient Information Leaflet if available from your pharmacist before you start taking fostamatinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
Take this medication by mouth with or without food as directed by your doctor, usually twice daily. The dosage is based on your medical condition and response to treatment.
Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.