fostamatinib disodium hexahydrate: clinical use

Prescribing considerations

• Initiation and ongoing supervision should be by a clinician experienced in haematological disease.
• Individualise treatment according to platelet response and tolerability without aiming to normalise the platelet count.
• Assess cardiovascular and hepatic status, infection risk, blood counts and concurrent medicines before treatment.
• Evaluate continued treatment if clinically important bleeding risk is not adequately reduced.
• Use additional caution in osteoporosis, active fractures or incomplete skeletal maturity because effects on bone remodelling remain uncertain.

Contraindications and cautions

• Hypersensitivity to fostamatinib or any tablet excipient.
• Pregnancy.
• Avoid use in severe hepatic impairment.
• Not for patients younger than 18 years because of adverse effects on actively growing bone in nonclinical studies.

Monitoring

• Platelet count and clinical bleeding.
• Blood pressure frequently until stable and regularly thereafter.
• Liver transaminases and bilirubin regularly; monitor more closely in hepatic impairment or possible UGT1A1 polymorphism.
• Full blood count, including absolute neutrophil count.
• Diarrhoea, infection and treatment-emergent interactions.

Clinical pharmacology

Fostamatinib is an oral prodrug rapidly converted in the gut to R406. R406 inhibits SYK-mediated B-cell receptor and Fc-receptor signalling, reducing antibody-mediated platelet clearance. R406 is highly protein-bound, metabolised mainly through CYP3A4 oxidation and UGT1A9 glucuronidation, and eliminated predominantly in faeces.

Formulation and product differences

• The 100 mg tablet is round, dark orange and marked “100” and “R”; it contains 23 mg sodium per tablet.
• The 150 mg tablet is oval, light orange and marked “150” and “R”; it contains 34 mg sodium per tablet.
• Both are film-coated tablets supplied in moisture-protective bottles containing desiccants.

Tablet

Route: Oral

Strengths: 100 mg