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 belzutifan (three 40 mg tablets) administered once daily, at the same time every day.

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. 3 If vomiting occurs any time after taking WELIREG, another dose should not be taken. The next dose should be taken the next day. Dose modifications Dose modifications for WELIREG for adverse reactions are summarised in Table 1.

2). 2). 5 x ULN and ≤ 3 x ULN and any AST or Child-Pugh B) hepatic impairment. 2). 1). No data are available. Method of administration WELIREG is for oral use. The tablets should be swallowed whole and may be taken with or without food. Tablets should not be split, crushed or chewed, as it is not known whether this impacts absorption of belzutifan.

Summary of the safety profile The safety of belzutifan has been evaluated in 576 patients with advanced solid tumours and VHL disease-associated localised tumours treated with 120 mg belzutifan once daily in clinical studies. 4 months).

3%). 2%). 2%). 6%). 7%). 4%). Tabulated list of adverse reactions Adverse reactions reported in the pooled dataset for patients treated with belzutifan (n=576) or reported from post-marketing use are listed in Table 2. These reactions are presented by 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). 8 Table 2: Adverse reactions in patients treated with belzutifan* System Organ Class All Grades Grade 3 – 4 Blood and lymphatic system disorders Anaemia† Very common Very common Nervous system disorders Dizziness Very common - Vascular disorders Haemorrhage‡# Very common Common Respiratory, thoracic and mediastinal disorders Dyspnoea Very common Common Hypoxia Very common Very common Gastrointestinal disorders Nausea Very common Uncommon General disorders and administration site conditions Fatigue Very common Common Investigations Weight increased Common Common *Adverse reaction frequencies presented in Table 2 may contain contributions from the underlying disease.

†Anaemia includes anaemia and haemoglobin decreased. ‡ Includes different bleeding events from different sites not listed individually. Haemorrhage terms that occurred in 5 or more patients treated with belzutifan were: haematuria, haemoptysis, contusion and epistaxis (any grade); and haematuria (grades 3-4).

4). 5% had Grade 4 anaemia. Median time to onset of anaemia was 29 days (range: 1 day to 27 months). Of the patients with anaemia, 22% received transfusions only, 20% of patients received ESAs only and 14% received both transfusion and ESAs.

8). Patients should be monitored for anaemia before initiation of and periodically throughout treatment with belzutifan. 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 until resolved to ≤ Grade 2 (see the prescribing information for ESAs for more information).

For recurrent Grade 3 anaemia, belzutifan should be discontinued. 2). 8). 5 Patients should be monitored for oxygen saturation with pulse oximetry before initiation of and periodically throughout treatment with belzutifan. For Grade 3 asymptomatic 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 symptomatic hypoxia, belzutifan should be withheld, hypoxia should be treated, and belzutifan should be resumed at a reduced dose. If symptomatic hypoxia continues to recur, treatment should be discontinued.

2). 3). The pregnancy status of women of childbearing potential should be verified prior to initiating treatment with belzutifan. 6). CNS haemorrhage in patients with VHL disease-associated CNS-haemangioblastomas (CNS-HB) CNS haemorrhage, including with fatal outcome, has been observed in patients with VHL disease- associated CNS-HB.

Physicians should be cautious of symptoms or signs of CNS haemorrhage in patients with VHL disease-associated CNS-HB being treated with belzutifan. Information about excipients This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1. 6).