Momelotinib

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.

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. MF is a myeloproliferative neoplasm associated with constitutive activation and dysregulated JAK signaling that contributes to inflammation and hyperactivation of ACVR1.

• Recommended dosage: 200 mg orally once daily with or without food. • Severe hepatic impairment (Child-Pugh Class C): Reduce the starting dose to 150 mg orally once daily.

None. None.

• Risk of Infections: Do not initiate OJJAARA in patients with an active infection. Monitor for signs and symptoms of infection, including reactivation of hepatitis B, and initiate appropriate treatment promptly. • Thrombocytopenia and Neutropenia: Manage by dose reduction or interruption. • Hepatotoxicity: Obtain liver tests before initiation of and periodically throughout treatment with OJJAARA. • Severe Cutaneous Adverse Reactions (SCARs): Monitor for signs and symptoms, and interrupt OJJAARA until etiology of reaction has been determined. • Major Adverse Cardiovascular Events (MACE): Monitor for symptoms, evaluate and treat promptly. • Thrombosis: Evaluate and treat symptoms of thrombosis promptly. • Malignancies: Monitor for development of secondary malignancies, particularly in current or past smokers.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Risk of Infections and Hepatitis B Reactivation • Thrombocytopenia and Neutropenia • Hepatotoxicity • Severe Cutaneous Adverse Reactions • Major Adverse Cardiovascular Events • Thrombosis • Malignancies • Symptom Exacerbation Following Interruption or Discontinuation of Treatment The most common adverse reactions (≥20% in either study) are thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.

• Organic Anion Transporting Polypeptide (OATP)1B1/B3 inhibitors: Monitor for adverse reactions. • Breast Cancer Resistance Protein (BCRP) substrates: Reduce rosuvastatin (BCRP substrate) dosage. Follow approved product information recommendations for other BCRP substrates.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store in original bottle to protect from moisture.