Ojjaara

Clinical summary

Indications and usage 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 ) Dosage and administration 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. 2.2 Laboratory Monitoring for Safety Obtain the following blood tests prior to starting treatment with OJJAARA, periodically during treatment, and as clinically indicated: • Complete blood count (CBC) with platelets [see Warnings and Precautions ( 5.2 )] • Hepatic panel [see Warnings and Precautions ( 5.3 )] 2.3 Dosage Modification for Hepatic Impairment The recommended starting dosage in patients with severe hepatic impairment (Child‑Pugh Class C) is 150 mg orally once daily [see Use in Specific Populations ( 8.6 )] . No dose adjustment is recommended for patients with mild or moderate hepatic impairment. 2.4 Dosage Modification for Adverse Reactions Manage hematologic and non‑hematologic adverse reactions as described in Table 1 . Table 1: Dose Modifications for OJJAARA-Related Adverse Reactions ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal. a Reinitiate or escalate treatment up to starting dosage as clinically appropriate. b May reinitiate treatment at 100 mg if previously dosed at 100 mg. c If baseline >2 × ULN. d If baseline >1.5 × ULN. e Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events per (CTCAE). Thrombocytopenia Dose Modification a Baseline Platelet Count Platelet Count ≥100 × 10 9 /L 20 × 10 9 /L to 5 × ULN (or >5 × baseline, if baseline is abnormal) and/or total bilirubin >2 × ULN (or >2 × baseline, if baseline is abnormal) Interrupt treatment until AST and ALT ≤2 × ULN or baseline c and total bilirubin ≤1.5 × ULN or baseline. d Restart OJJAARA at a daily dose of 50 mg below the last given dose. b If reoccurrence of ALT or AST elevations >5 × ULN, permanently discontinue OJJAARA. Other Non‑Hematologic Dose Modification a Grade 3 or higher e Interrupt treatment until the toxicity resolves to Grade 1 or lower (or baseline). Restart OJJAARA at a daily dose of 50 mg below the last given dose. b Discontinue OJJAARA in patients unable to tolerate 100 mg once daily. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • 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. ( 5.1 ) • Thrombocytopenia and Neutropenia: Manage by dose reduction or interruption. ( 5.2 ) • Hepatotoxicity: Obtain liver tests before initiation of and periodically throughout treatment with OJJAARA. ( 5.3 ) • Severe Cutaneous Adverse Reactions (SCARs): Monitor for signs and symptoms, and interrupt OJJAARA until etiology of reaction has been determined. ( 5.4 ) • Major Adverse Cardiovascular Events (MACE): Monitor for symptoms, evaluate and treat promptly. ( 5.5 ) • Thrombosis: Evaluate and treat symptoms of thrombosis promptly. ( 5.6 ) • Malignancies: Monitor for development of secondary malignancies, particularly in current or past smokers. ( 5.7 ) • Symptom Exacerbation Following Interruption or Discontinuation of Treatment: Manage with supportive care and consider restarting OJJAARA. ( 5.8 ) 5.1 Risk of Infections Serious (including fatal) infections (e.g., bacterial and viral, including COVID ‑ 19) occurred in 13% of patients treated with OJJAARA. Infections regardless of grade occurred in 38% of patients treated with OJJAARA [see Adverse Reactions ( 6.1 )] . Delay starting therapy with OJJAARA until active infections have resolved. Monitor patients receiving OJJAARA for signs and symptoms of infection and initiate appropriate treatment promptly. Hepatitis B Reactivation Hepatitis B viral load (HBV ‑ DNA titer) increases, with or without associated elevations in alanine transaminase (ALT) or aspartate transaminase (AST), have been reported in patients with chronic hepatitis B virus (HBV) infection taking Janus Kinase (JAK) inhibitors, including OJJAARA. The effect of OJJAARA on viral replication in patients with chronic HBV infection is unknown. In patients with HBV infection