Omjjara

Treatment should be initiated and monitored by physicians experienced in the use of anti-cancer medicinal products. Posology Omjjara should not be used in combination with other JAK inhibitors. The recommended dose is 200 mg once daily.

4). Dose modifications Dose modifications should be considered for haematologic and non-haematologic toxicities (table 1). 5 × ULN or baseline Restart Omjjara at a daily dose of 50 mg below the last given doseb If reoccurrence of ALT or AST elevations >5 × ULN, permanently discontinue Omjjara Other non-haematologic Dose modificationa Grade 3 or higherc Grade 2 or higherc bleeding Interrupt treatment until the toxicity resolves to Grade 1 or lower (or baseline) Restart Omjjara at a daily dose of 50 mg below the last given doseb ANC = absolute neutrophil count; 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 Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

Treatment with Omjjara should be discontinued in patients unable to tolerate 100 mg once daily. Duration of use Treatment may be continued for as long as the benefit-risk remains positive for patients, as assessed by the treating physician.

5 Missed dose If a dose of Omjjara is missed, the next scheduled dose should be taken the following day. Two doses should not be taken at the same time to make up for the missed dose. 2). Renal impairment No dose adjustment is required for patients with renal impairment (>15 mL/min).

Omjjara has not been studied in patients with end-stage renal disease. 4). 2). Paediatric population The safety and efficacy of Omjjara in children and adolescents less than 18 years of age have not been established. No data are available.

2).

Summary of the safety profile The safety of Omjjara, evaluated in three randomised, active-controlled, multicentre studies in adults with myelofibrosis (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), is presented below (table 2). Among patients treated with Omjjara 200 mg daily in the randomised treatment period of the clinical trials (n = 448), the most common adverse reactions were diarrhoea (23%), thrombocytopenia (21%), nausea (17%), headache (13%), dizziness (13%), fatigue (12%), asthenia (11%), abdominal pain (11%), and cough (10%).

The most common severe adverse reaction (≥ Grade 3) was thrombocytopenia (12%). 5%). The most common adverse reaction requiring dosage reduction and/or treatment interruption was thrombocytopenia (7%). 1). Adverse reactions are listed by MedDRA system organ classification (SOC) and by frequency.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Frequencies are defined as:

Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1 000 to <1/100 Rare: ≥1/10 000 to <1/1 000 Table 2: Summary of adverse reactions reported in Phase 3 studies in adults with myelofibrosis System organ class (SOC) Adverse reaction Frequency category Infections and infestations Urinary tract infection, upper respiratory tract infection, pneumonia, nasopharyngitis, COVID-19, cystitis, bronchitis, oral herpes, sinusitis, herpes zoster, cellulitis, respiratory tract infection, sepsis, lower respiratory tract infection, oral candidiasis, skin infection, gastroenteritis Common COVID-19 pneumonia Uncommon Blood and lymphatic system disorders Thrombocytopeniaa Very common Neutropeniab Common Metabolism and nutrition disorders Vitamin B1 deficiency Common Nervous system disorders Dizziness, headache Very common Syncope, peripheral neuropathyc, paraesthesia Common Eye disorders Blurred vision Common Ear and labyrinth disorders Vertigo Common 10 System organ class (SOC) Adverse reaction Frequency category Vascular disorders Hypotension, haematoma, flushing Common Respiratory, thoracic and mediastinal disorders Cough Very common Gastrointestinal disorders Diarrhoea, abdominal pain, nausea Very common Vomiting, constipation Common Skin and subcutaneous tissue disorders Rashd Common Musculoskeletal and connective tissue disorders Arthralgia, pain in extremity Common General disorders and administration site conditions Asthenia, fatigue Very common Pyrexia Common Investigations Alanine transaminase (ALT) increased, aspartate transaminase (AST) increased Common Injury, poisoning and procedural complications Contusion Common a Thrombocytopenia includes platelet count decreased.

8). Omjjara should not be initiated in patients with active infections. Physicians should carefully observe patients receiving Omjjara for signs and symptoms of infection (including but not limited to fever, cough, diarrhoea, vomiting, nausea, and pain upon urination) 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 JAK inhibitors, including Omjjara.

The effect of Omjjara on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection who receive Omjjara should have their chronic HBV infection treated and monitored according to clinical HBV guidelines.

8). A complete blood count including platelet count should be obtained before initiating treatment with Omjjara, periodically during treatment, and as clinically indicated. 2). Hepatic monitoring Liver function tests should be obtained before initiating treatment with Omjjara, periodically during treatment, and as clinically indicated.

2). Major adverse cardiovascular events (MACE) In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of MACE, defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke, was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors.

Events of MACE have been reported in patients receiving Omjjara, however, a causal relationship has not been established. Prior to initiating or continuing therapy with Omjjara, the benefits and risks for the individual patient should be considered particularly in patients 65 years of age and older, patients who are current or past long-time smokers, and patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors.

1. 6).