Rytelo

Rytelo should be administered and monitored under the supervision of physicians and healthcare professionals who are experienced in haematologic disease and treatment. Complete blood cell count and liver function tests are recommended before administration of each dose.

4). 6). 1 mg/kg body weight administered as an intravenous infusion once every 4 weeks. Rytelo should be discontinued if patients do not experience a reduction in red blood cell (RBC) transfusion burden after 24 weeks of treatment (6 doses) or if unacceptable toxicity occurs at any time.

Premedication for potential infusion-related reactions Patients should be premedicated with diphenhydramine (25 to 50 mg) and hydrocortisone (100 to 200 mg), or equivalent, at least 30 minutes before dosing with Rytelo. 4). Dose modifications Recommended dose reductions for all Grade 3 and Grade 4 adverse reactions are found in Table 1.

The management of Grade 3 and Grade 4 adverse reactions may require a dose delay, dose reduction, or treatment discontinuation and are presented in Table 2, Table 3 and Table 4. 4 mg/kg. 0 × 109/L or platelets are less than 50 × 109/L.

Modify dose as described in Table 2. 03. b Grade 3: severe; Grade 4: life-threatening Non-haematologic adverse reactions Dose administration modifications for infusion-related reactions are described in Table 3. , 125 mL/h) Third • For Grade 2, stop infusion.

03. b Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening Dose modifications for other adverse drug reactions, including elevated liver function tests, are described in Table 4. 03. b Grade 1: mild; Grade 3: severe; Grade 4: life-threatening Missed doses If a planned dose is missed, the patient should be administered Rytelo as soon as possible and dosing continued as prescribed with 4 weeks between doses.

Special populations Elderly No dose adjustments are required in elderly patients (≥ 65 years of age). Renal impairment No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance [CrCL] 30 to ˂ 90 mL/min).

2). 5× to 3× ULN (Grade 2) and any AST). 2). Paediatric population The safety and efficacy of Rytelo in children and adolescents aged 28 days to less than 18 years have not yet been established. No data are available. There is no relevant use of Rytelo in paediatric patients aged less than 28 days.

Summary of the safety profile The most common adverse reactions with Rytelo were thrombocytopenia (94%), leukopenia (93%), neutropenia (92%), aspartate aminotransferase (AST) increased (48%), alanine aminotransferase (ALT) increased (42%), alkaline phosphatase (ALP) increased (41%), asthenia (26%) and headache (16%).

The most commonly reported severe adverse reactions (Grade ≥ 3) were neutropenia (69%) and thrombocytopenia (63%). 1%). The frequency of treatment discontinuation due to adverse reactions was 13%. 3%). The frequency of dose reduction or dose delay due to adverse reactions is 65%.

The most common adverse reactions leading to dose modification or interruption were neutropenia (51%) and thrombocytopenia (45%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on pooled data from the clinical trials in 175 patients with low to intermediate-1 risk MDS, transfusion-dependent anaemia and were either relapsed or refractory to or ineligible for ESA treatment and treated with imetelstat at the recommended dose.

8 months. The adverse reactions are listed below by MedDRA system organ class and by frequency within each system organ class, with the most frequent adverse reactions listed first. Frequencies were 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); very rare (˂ 1/10 000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in decreasing order of seriousness. 6% a Urinary tract infection includes urinary tract infection, Escherichia urinary tract infection, and cystitis. b Sepsis includes sepsis, enterococcal sepsis, escherichia sepsis, neutropenic sepsis, and urosepsis.

c Thrombocytopenia (platelet count decreased), neutropenia (neutrophil count decreased), leukopenia (white blood cell count decreased), AST increased, ALP increased, and ALT increased are based on laboratory values. d Infusion-related reactions include abdominal pain, abdominal pain upper, arthralgia, asthenia, back pain, bone pain, chest pain, diarrhoea, discomfort, dyspnoea, erythema, flushing, headache, hyperhidrosis, hypertension, hypertensive crisis, hypotension, illness, malaise, nausea, non-cardiac chest pain, oedema peripheral, palmar erythema, pruritus, pyrexia, spinal pain, urticaria, and vomiting.

8). Complete blood cell counts should be monitored prior to each dose of Rytelo, weekly following administration of the first two doses, and for any case of Grade 3 or Grade 4 thrombocytopenia or as clinically indicated. Patients with Grade 3 or Grade 4 thrombocytopenia should be monitored for bleeding events as a precaution.

The need for platelet transfusions should be assessed as clinically appropriate. Patients should be advised to report any signs or symptoms of bruising or bleeding immediately. 2). 8), and febrile neutropenia may occur. Complete blood cell counts should be monitored prior to each dose of Rytelo, weekly following administration of the first two doses, and for any case of Grade 3 or Grade 4 neutropenia.

Patients with Grade 3 or Grade 4 neutropenia should be monitored for infections, including sepsis as a precaution. Granulocyte-colony stimulating factors and anti-infective therapies should be administered as clinically indicated. Patients should be advised to report any signs or symptoms of neutropenia, such as fever or infection immediately.

2). 8). The most common symptoms were headache and back pain. Other notable adverse reactions were Grade 3 hypotension, hypertension, hypertensive crisis, and non-cardiac chest pain. Patients usually experienced an infusion-related reaction during or shortly after the end of the infusion.

2). Patients should be monitored for adverse reactions for at least one hour after the infusion has been completed. 2). Embryo-foetal toxicity 7 Based on findings in animals, Rytelo may cause embryo-foetal harm when administered to a pregnant woman.

3). Pregnant women should be advised of the potential risk to a foetus. 6). 8% of the World Health Organization (WHO) recommended maximum daily intake of 2 g sodium for an adult. 6). This should be considered in relation to the total sodium intake to the patient from all sources per day.

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