Overview
11 DESCRIPTION OJJAARA contains momelotinib dihydrochloride monohydrate, which is a kinase inhibitor with the chemical name N‑(Cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide dihydrochloride monohydrate. It has a molecular formula of C 23 H 22 N 6 O 2 ● 2HCl ● H 2 O, molecular weight of 505.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2 V617F , which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Momelotinib and its major human circulating metabolite, M21, have higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2). Momelotinib and M21 additionally inhibit activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2), which produces subsequent inhibition of liver hepcidin expression and increased iron availability resulting in increased red blood cell production.
Indications
- 1 INDICATIONS AND USAGE OJJAARA is indicated for the treatment of intermediate or high‑risk myelofibrosis (MF), including primary MF or secondary MF [post‑polycythemia vera (PV) and post‑essential thrombocythemia (ET)], in adults with anemia. OJJAARA is a kinase inhibitor indicated for the treatment of intermediate or high‑risk myelofibrosis (MF), including primary MF or secondary MF [post‑polycythemia vera (PV) and post‑essential thrombocythemia (ET)], in adults with anemia. ( 1 )
Common Doses
- 200 mg
- 150 mg
- 100 mg
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Recommended dosage: 200 mg orally once daily with or without food. ( 2.1 ) • Severe hepatic impairment (Child-Pugh Class C): Reduce the starting dose to 150 mg orally once daily. ( 2.3 ) 2.1 Recommended Dosage The recommended dosage of OJJAARA is 200 mg orally once daily. OJJAARA may be taken with or without food. Swallow OJJAARA tablets whole. Do not cut, crush, or chew tablets. If a dose of OJJAARA is missed, the next scheduled dose should be taken the following day. 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Risk of Infections and Hepatitis B Reactivation [see Warnings and Precautions ( 5.1 )] • Thrombocytopenia and Neutropenia [see Warnings and Precautions ( 5.2 )] • Hepatotoxicity [see Warnings and Precautions ( 5.3 )] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.4 )] • Major Adverse Cardiovascular Events [see Warnings and Precautions ( 5.5 )] • Thrombosis [see Warnings and Precautions ( 5.6 )] • Malignancies [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS • Organic Anion Transporting Polypeptide (OATP)1B1/B3 inhibitors: Monitor for adverse reactions. ( 7.1 ) • Breast Cancer Resistance Protein (BCRP) substrates: Reduce rosuvastatin (BCRP substrate) dosage. Follow approved product information recommendations for other BCRP substrates. ( 7.2 ) 7.1 Effect of Other Drugs on OJJAARA Organic Anion Transporting Polypeptide (OATP)1B1/B3 Inhibitors Momelotinib is an OATP1B1/B3 substrate.