Overview
11 DESCRIPTION VONJO contains pacritinib citrate, a kinase inhibitor with the chemical name (2E,16E)-11-[2-(pyrrolidin-1-yl)ethoxy]-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene citrate and a molecular weight of 664.7 as citrate salt and 472.59 as a free base.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, FMS-like tyrosine kinase 3 (FLT3), and interleukin 1 receptor associated kinase-1 (IRAK1) which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Pacritinib is also an inhibitor of activin A receptor, type 1/activin receptor like-kinase 2 (ACVR1/ALK2). MF is often associated with dysregulated JAK2 signaling. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2).
Indications
- 1 INDICATIONS AND USAGE VONJO is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 10 9 /L. This indication is approved under accelerated approval based on spleen volume reduction [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Common Doses
- 200 mg
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage is 200 mg orally twice daily ( 2.1 ). May be taken with or without food ( 2.1 ). 2.1 Recommended Dosage The recommended dosage of VONJO is 200 mg orally twice daily. VONJO may be taken with or without food. Swallow capsules whole. Do not open, break, or chew capsules. Patients who are on treatment with other kinase inhibitors before the initiation of VONJO must taper or discontinue according to the prescribing information for that drug. 2.
Contraindications
- 4 CONTRAINDICATIONS VONJO is contraindicated in patients concomitantly using strong CYP3A4 inhibitors or inducers as these medications can significantly alter exposure to pacritinib, which may increase the risk of adverse reactions or impair efficacy [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.3 )] . Concomitant use of strong CYP3A4 inhibitors or inducers ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage [see Warnings and Precautions ( 5.1 )] Diarrhea [see Warnings and Precautions ( 5.2 )] Thrombocytopenia [see Warnings and Precautions ( 5.3 )] Prolonged QT Interval [see Warnings and Precautions ( 5.4 )] Major Adverse Cardiac Events [see Warnings and Precautions ( 5.5 )] Thrombosis [see Warnings and Precautions ( 5.6 )] Secondary Malignancies [see Warnings and Precautions ( 5.7 )] Risk of Infection [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Co-administration of VONJO with moderate CYP3A4 inhibitors can increase the exposure to pacritinib. Monitor for increased adverse reactions of VONJO when administered with moderate CYP3A4 inhibitors ( 7.1 ). VONJO is an inhibitor of P-gp, BCRP, and CYP1A2 and an inducer of CYP3A4 and CYP2C19. Monitor patients concomitantly receiving substrates of these transporters and enzymes, and adjust dose of the substrates as needed ( 7.2 ). VONJO may reduce the effectiveness of hormonal contraceptives ( 7.2 ) 7.