Fostamatinib
Indications
Fostamatinib is used for:
Immune Thrombocytopenia (ITP)
Adult Dose
Immune Thrombocytopenia (ITP)
Indicated for thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment
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
Child Dose
<18 years: Safety and efficacy not established
Renal Dose
Administration
May take with or without food
Contra Indications
Precautions
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
Pregnancy-Lactation
Pregnancy
There are no available data in pregnant women to inform the drug-associated risk
In animal reproduction studies, administration of fostamatinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes that were directly attributed to exposure in utero to R406 at maternal exposures (AUC) as low as 0.3 and 10 times the exposure in patients at the maximum recommended human dose (MRHD), respectively
Verify pregnancy status in females with reproductive potential before initiating fostamatinib; advise pregnant females of the potential risk to a fetus
Fertility
There are no data on the effect of fostamatinib on human fertility
Based on the finding of reduced pregnancy rates in animal studies, fostamatinib may affect female fertility
Contraception
Females: Use effective contraception during treatment and for at least 1 month after the last dose
Lactation
Unknown if distributed in human breast milk
In rodents, R406 was detected in maternal milk in concentrations 5- to 10-fold higher than in maternal plasma
Advise a lactating woman not to breastfeed during treatment with fostamatinib and for at least 1 month after the last dose
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Interactions
Adverse Effects
Side effects of Fostamatinib :
>10%
Diarrhea (10-21%)
Hypertension (9-17%)
Nausea (3-16%)
1-10%
Dizziness (2-8%)
Rash (1-8%)
Respiratory infection (4-7%)
Abdominal pain (1-5%)
ALT/AST >5 and ≤10x ULN (5%)
Fatigue (4%)
Chest pain (2-3%)
Neutropenia (2-3%)
ALT/AST >3 and ≤5x ULN (3%)
Hypertension, severe (2%)
Diarrhea, severe (1%)
Dizziness, severe (1%)
Chest pain, severe (1%)
Neutropenia, severe (1%)
ALT/AST &g3;10x ULN (1%)
Mechanism of Action
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