WELIREG

Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. Posology The recommended dose of Welireg is 120 mg (three 40 mg tablets) administered orally once daily, with or without food.

Tablets should be swallowed whole. Treatment should continue until disease progression or unacceptable toxicity occurs. Missed dose If a dose of Welireg is missed, it can be taken as soon as possible on the same day. The regular daily dose should be resumed the next day.

Extra tablets should not be taken to make up for the missed dose. If vomiting occurs any time after taking Welireg, the dose should not be retaken. The next dose should be taken the next day. 4).

Table 1:

Recommended Dose Modifications Adverse Reactions Severity* Dose Modification Grade 3: Haemoglobin (Hgb < 8g /dL) transfusion indicated • Withhold until resolved to ≤ Grade 2 (Hgb ≥ 8 g/dL). • Resume at the same or reduced dose (reduce by 40 mg), consider discontinuing depending on the severity and persistence of anaemia.

4) Grade 4: Life- threatening or urgent intervention indicated • Withhold until resolved to ≤ Grade 2 (Hgb ≥ 8 g/dL). • Resume at a reduced dose (reduce by 40 mg) or permanently discontinue. g. pulse oximeter < 88%) intermittent supplemental oxygen • Consider withholding until resolved.

• Resume at the same dose or at a reduced dose depending on the severity of hypoxia. g. pulse oximeter <88% or PaO² <=55 mm Hg) • Withhold until resolved to ≤ Grade 2 • Resume at reduced dose (reduce by 40 mg) or discontinue depending on the severity and persistence of hypoxia.

4) Grade 4: Life- threatening • Permanently discontinue. Other Adverse Grade 3 • Withhold dosing until resolved to Adverse Reactions Severity* Dose Modification ≤ Grade 2. • Consider resuming at a reduced dose (reduce by 40 mg). • Permanently discontinue upon recurrence of Grade 3.

8) Grade 4 • Permanently discontinue. 0 Special Populations Elderly (≥ 65 years old) No dose adjustment is recommended for elderly patients. 2). 73 m2). 2). Hepatic impairment No dose adjustment of Welireg is recommended in patients with mild hepatic impairment.

2). Paediatric population The safety and efficacy of Welireg in children less than 18 years of age has not yet been established. No data are available. Method of administration Welireg is for oral use. It should be swallowed whole and may be taken with or without food.

von Hippel-Lindau (VHL) disease associated tumours Summary of the safety profile The safety of belzutifan was evaluated in an open-label Phase 2 clinical study (LITESPARK-004), in 61 patients with VHL disease-associated RCC and who did not require immediate nephrectomy or partial nephrectomy.

Patients were treated with 120 mg belzutifan once daily. 5). The most common adverse reactions with belzutifan were anaemia (90%), fatigue (71%), dizziness (44%) and nausea (36%). The most common Grade 3 or 4 adverse reactions were anaemia (10%), and fatigue (5%).

Serious adverse reactions occurred in 5% of patients who received belzutifan, including anaemia, dyspnoea and hypoxia (1 patient each). Dose interruption of belzutifan due to adverse reactions occurred in about 23% of patients. 9%). 5% of patients.

6%). Tabulated list of adverse reactions. Adverse reactions reported in clinical studies of belzutifan are listed in the table below by MedDRA system organ class and by frequency. 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), and very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Table 2:

Adverse drug reactions in patients with VHL disease-associated tumours treated with belzutifan 120 mg Once Daily Adverse Drug Reaction All Grades Grade 3 – 4 Blood and lymphatic disorders Anaemia Very common Common Nervous system disorders Dizziness Very common Very rare Respiratory, thoracic and mediastinal disorders Dyspnoea Very common Common Hypoxia Common Common Gastrointestinal disorders Nausea Very common Very rare General disorders and administration site disorders Fatigue Very common Common Investigations Weight Increased Very Common Common The safety of belzutifan was also evaluated in a Phase 1 clinical study (Study-001), in 58 patients with non-VHL disease-associated advanced solid tumours, treated with belzutifan 120 mg once daily.

8). 1). For patients who develop Grade 3 anaemia, belzutifan should be withheld and patients should be treated according to standard medical practice, including erythropoiesis-stimulating agent (ESA) administration and/or transfusion until resolved to ≤ Grade 2, then resume at the same or reduced dose.

For recurrent Grade 3 anaemia, consider discontinuing belzutifan. 2). 2). 1). In light of the risk of hypoxia, smoking cessation is recommended. For Grade 2 hypoxia, providing supplemental oxygen and continuing or withholding treatment should be considered.

If withheld, belzutifan should be resumed at a reduced dose. For patients who have Grade 3 hypoxia, belzutifan should be withheld, hypoxia treated, and dose reduction should be considered. If Grade 3 hypoxia continues to recur, treatment should be discontinued.

2). Patients treated with belzutifan must be given the patient alert card. Embryo-foetal toxicity Based on findings in animals, belzutifan may cause foetal harm, including foetal loss, in humans. 3). 6). 6). Advise male patients with female partners who are pregnant to use a barrier method of contraception during treatment with belzutifan and 1 week after the last dose.

Information about some of the ingredients This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

1.