fostamatinib

Action and Spectrum

Actions and Spectrum: 

Actions: 

Fostamatinib hinders the signaling of IgG Fc gamma receptors mediated by Syk kinase, leading to the suppression of mast cell, macrophage, and B-cell activation. This, in turn, mitigates inflammatory responses and prevents associated tissue damage. 

Spectrum: 

Fostamatinib demonstrates its range of effects by blocking spleen tyrosine kinase (SYK). Functioning as a tyrosine kinase inhibitor, it disrupts signaling pathways mediated by SYK, influencing immune response mechanisms and inflammatory processes. This specific mode of action renders fostamatinib efficacious in managing conditions linked to irregular immune responses, including rheumatoid arthritis and immune thrombocytopenia. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Nausea (3-16%) 

Diarrhea (10-21%) 

HTN (9-17%) 

1-10 % 

Severe HTN (2%) 

Rash (1-8%) 

Abdominal pain (1-5%) 

Dizziness (2-8%) 

Severe Dizziness (1%) 

Fatigue (4%) 

Severe chest pain (1%) 

Neutropenia (2-3%) 

Severe Neutropenia (1%) 

ALT/AST > 5 and ≤ 10 x ULN (5%) 

ALT/AST > 3 and ≤ 5 x ULN (5%) 

Respiratory infection (4-7%) 

Severe Diarrhea (1%) 

Black Box Warning

Black Box Warning: 

Fostamatinib has the potential to elevate blood pressure, occasionally reaching hazardous levels. Additionally, it may lead to intense diarrhea, liver issues, and susceptibility to infections.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Renal impairment 
• HTN 
• Raised LFTs 
• Diarrhea 
• Neutropenia 
• Hepatic impairment 
• Drug interactions 
• Pregnancy  
• Breastfeeding 
• Pediatrics

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category.

Pharmacology

Pharmacology: 

Fostamatinib is a medication used to address a reduced platelet count resulting from immune thrombocytopenia. This condition hinders proper blood clotting due to a lower-than-normal platelet count. Platelets play a crucial role in blood coagulation, being the first responders to injury sites, facilitating wound clotting, and preventing excessive bleeding. 

Pharmacodynamics: 

A tyrosine kinase inhibitor is known for its effectiveness against spleen tyrosine kinase (SYK). 

The main metabolite of fostamatinib, R406, disrupts the signal transduction of Fc-activating receptors and the B-cell receptor; R406 alleviates the antibody-mediated destruction of platelets. 

Pharmacokinetics: (active metabolite) 

Absorption 

The bioavailability of  R406 (active metabolite) is 55% 

Distribution 

Protein-bound is 98.3% 

The volume of distribution (ss) is 256 L  

Metabolism 

A prodrug that undergoes conversion in the gastrointestinal tract by alkaline phosphatase to yield the principal active metabolite, R406. 

R406 undergoes extensive metabolism, mainly through pathways involving CYP450-mediated oxidation (specifically by CYP3A4) and glucuronidation (by UDP glucuronosyltransferase [UGT]1A9). 

Elimination and Excretion 

The half-life is 15 hours (R406) 

The metabolite is excreted 80% in feces and 20% in urine. 

Adminstartion

Administration: 

Fostamatinib is available in tablet form for oral administration and is typically taken twice daily, with or without food. It’s advisable to take fostamatinib at consistent times each day. Follow the prescription instructions carefully. Adhere to the prescribed dosage precisely, avoiding any deviation in quantity or frequency beyond the doctor’s recommendations. 

Depending on your response to treatment or if you encounter specific side effects, your doctor may consider reducing, interrupting, or discontinuing your treatment. In case your platelet count does not reach a specified level after 12 weeks of treatment, discontinuation of the treatment might be necessary. Keep an open dialogue with your doctor about your well-being throughout the treatment. 

Feel free to request a copy of the manufacturer’s patient information from your pharmacist or doctor.

Patient Information Leaflet

Patient information leaflet 

Generic Name: fostamatinib 

Pronounced: foss-tam-AH-ti-nib 

Why do we use fostamatinib? 

Studies on fostamatinib have explored its potential for the treatment of rheumatoid arthritis and immune thrombocytopenic purpura (ITP). The FDA accorded it orphan drug classification, which made its clearance under the trade name Tavalisse, on April 17, 2018, for ITP use a noteworthy milestone. Because of its ability to inhibit SYK kinase, fostamatinib has gained attention as a potential treatment option for  ARDS (acute respiratory distress syndrome) in severe COVID-19 cases.