Fostamatinib disodium hexahydrate

Fostamatinib disodium hexahydrate is a phosphate salt form of fostamatinib, a spleen tyrosine kinase (Syk) inhibitor with immunomodulatory activity. It is primarily used in the treatment of chronic immune thrombocytopenia (ITP), a disorder that leads to excessive bruising and bleeding due to a low number of platelets in the blood. Fostamatinib disodium hexahydrate works by inhibiting the activity of Syk, a key enzyme involved in the signaling pathways that lead to the destruction of platelets in patients with ITP.

Medical Uses

Fostamatinib disodium hexahydrate is indicated for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment. It offers a therapeutic option for patients who have struggled to maintain stable platelet counts with other therapies.

Mechanism of Action

The active ingredient, fostamatinib, is a prodrug that is converted in the body to its active form, R406. R406 inhibits the Syk enzyme, which plays a crucial role in the activation of immune cells involved in the destruction of platelets in ITP patients. By inhibiting Syk, fostamatinib reduces the immune-mediated destruction of platelets, thereby increasing platelet counts and reducing the risk of bleeding.

Pharmacokinetics

After oral administration, fostamatinib is rapidly absorbed and converted to its active metabolite, R406. It exhibits a bioavailability of approximately 55%. The drug is extensively metabolized in the liver, primarily through pathways involving cytochrome P450 enzymes. It is excreted in both urine and feces, with a terminal half-life of approximately 15 hours for R406.

Adverse Effects

Common adverse effects of fostamatinib disodium hexahydrate include hypertension, diarrhea, nausea, dizziness, and neutropenia. Patients should be monitored for the development of hypertension and managed as appropriate. Liver enzyme elevations have also been observed, necessitating regular monitoring of liver function tests.

Contraindications

Fostamatinib disodium hexahydrate is contraindicated in patients with known hypersensitivity to the drug or any of its components. Caution is advised in patients with a history of liver disease or those taking other medications that are metabolized by the liver.

Drug Interactions

Fostamatinib may interact with other medications metabolized by cytochrome P450 enzymes, leading to altered drug levels and effects. It is important to assess all medications taken by the patient, including over-the-counter drugs and herbal supplements, to avoid potential interactions.

Regulatory Approval

Fostamatinib disodium hexahydrate has been approved by regulatory agencies in several countries for the treatment of chronic ITP. The approval was based on clinical trials demonstrating its efficacy in increasing platelet counts and reducing bleeding episodes in ITP patients.