pacritinib + clarithromycin

Pacritinib is an oral small molecule kinase inhibitor indicated for the treatment of adults with intermediate or high-risk primary or secondary myelofibrosis (including post-polycythemia vera and post-essential thrombocythemia myelofibrosis) with a platelet count below 50 × 10⁹/L. It selectively inhibits Janus kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), as well as other kinases such as CSF1R and IRAK1, which are involved in hematopoiesis and immune function. Pacritinib does not inhibit JAK1 at clinically relevant concentrations[2][3][4]. Clarithromycin is a semisynthetic macrolide antibiotic used to treat various bacterial infections by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit. It also inhibits hepatic CYP3A4 enzyme activity[6][8]. When co-administered, clarithromycin significantly increases pacritinib exposure due to CYP3A4 inhibition; this interaction can lead to higher plasma levels of pacritinib[4].