Bosutinib

Bosutinib tablets are indicated for the treatment of: Adult patients with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy . Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy . Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information.

12.1 Mechanism of Action Bosutinib is a TKI. Bosutinib inhibits the BCR-ABL kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells.

Systemic exposure to Bosutinib reflects F ≈ 49%–61% systemic availability after standard oral Bosutinib administration absorption kinetics and mixed metabolic conjugation and unchanged urinary excretion across bosutinib regimens, sustaining receptor engagement across a Terminal t½ estimated at 4–13 hrs depending on renal/hepatic reserve (Bosutinib) half-life window (time to peak concentration spans 1 to 4 hrs under bosutinib maintenance response profile).

Dosing protocols (50 mg/1 Capsule or 100 mg/1 Capsule or 400 mg/1 Tablet, Film Coated or 100 mg/1 Tablet, Film Coated or 500 mg/1 Tablet, Film Coated) balance efficacy (78.00% patient satisfaction across 14 logs) against nausea (10% of reports), headache (8.6% of reports), fatigue (7.7% of reports), with strict avoidance in bosutinib tablets are contraindicated in patients with a history of hypersensitivity to bosutinib.; reactions have included anaphylaxis .; hypersensitivity to bosutinib..