Overview
11 DESCRIPTION Fostamatinib is a tyrosine kinase inhibitor. TAVALISSE is formulated with the disodium hexahydrate salt of fostamatinib, a phosphate prodrug that converts to its pharmacologically active metabolite, R406, in vivo . The chemical name for fostamatinib disodium hexahydrate is disodium (6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fostamatinib is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK). The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor. The fostamatinib metabolite R406 reduces antibody-mediated destruction of platelets. 12.2 Pharmacodynamics Mean treatment-related increases of 2.93 mmHg in systolic blood pressure and 3.53 mmHg in diastolic blood pressure over placebo were observed following TAVALISSE doses of 100 mg twice daily for 28 days. About 31% of patients in the TAVALISSE group experienced blood pressures ≥140/90 mmHg compared to 15% of patients in the placebo group.
Indications
- 1 INDICATIONS AND USAGE TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. TAVALISSE is a kinase inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Common Doses
- 100 mg
- 150 mg
- 300 mg
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Initiate TAVALISSE at 100 mg orally twice daily with or without food. After 4 weeks, increase to 150 mg twice daily, if needed, to achieve platelet counts of at least 50 × 10 9 /L as necessary to reduce the risk of bleeding. ( 2.1 ) Manage adverse reactions using dose reduction, interruption of treatment, or discontinuation. ( 2.3 ) Discontinue TAVALISSE after 12 weeks of treatment if the platelet count does not increase to a level sufficient to avoid clinically important bleeding. ( 2.5 ) 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically important adverse reactions, that can become serious are described elsewhere in the labeling: Hypertension [ see Warnings and Precautions (5.1) ] Hepatotoxicity [ see Warnings and Precautions (5.2) ] Diarrhea [ see Warnings and Precautions (5.3) ] Neutropenia [ see Warnings and Precautions (5.4) ] The most common adverse reactions (≥5% and more than placebo) are diarrhea, hypertension, nausea, respiratory infection, dizziness, ALT/AST increased, rash, abdominal pain, fatigue, chest pain and neutropenia. ( 6.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Concomitant use with a strong CYP3A4 inhibitor increases exposure to R406 (the major active metabolite).( 7 ) Strong CYP3A4 Inducers: Concomitant use is not recommended. ( 7 ) 7.1 Effect of Other Drugs on TAVALISSE Strong CYP3A4 Inhibitors Concomitant use with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.