RYBELSUS

Posology The starting dose of semaglutide is 3 mg once daily for one month. After one month, the dose should be increased to a maintenance dose of 7 mg once daily. After at least one month with a dose of 7 mg once daily, the dose can be increased to a maintenance dose of 14 mg once daily to further improve glycaemic control.

The recommended single daily maintenance doses are 7 mg or 14 mg. The maximum recommended single daily dose of semaglutide is 14 mg. Rybelsus should always be used as one tablet per day. Taking more than one tablet a day should not be done to achieve the effect of a higher dose.

2. When semaglutide is used in combination with metformin and/or a sodium-glucose co- transporter-2 inhibitor (SGLT2i) or thiazolidinedione, the current dose of metformin and/or SGLT2i or thiazolidinedione can be continued. 8). Self-monitoring of blood glucose is not needed in order to adjust the dose of semaglutide.

Blood glucose self-monitoring is necessary to adjust the dose of sulfonylurea and insulin, particularly when semaglutide is started and insulin is reduced. A stepwise approach to insulin reduction is recommended. Missed dose If a dose is missed, the missed dose should be skipped and the next dose should be taken the following day.

Elderly No dose adjustment is required based on age. Renal impairment No dose adjustment is required for patients with mild, moderate or severe renal impairment. 2) Hepatic impairment No dose adjustment is required for patients with hepatic impairment.

Experience with the use of semaglutide in patients with severe hepatic impairment is limited. 2). Paediatric population The safety and efficacy of Rybelsus in children and adolescents below 18 years have not been established. No data are available.

Method of administration Rybelsus is a tablet for once-daily oral use. 2). – It should be swallowed whole with a sip of water (up to half a glass of water equivalent to 120 ml). Tablets should not be split, crushed or chewed, as it is not known whether this impacts absorption of semaglutide.

– Patients should wait at least 30 minutes before eating, drinking or taking other oral medicinal products. 2).

Summary of the safety profile In 10 phase 3a trials, 5 707 patients were exposed to semaglutide alone or in combination with other glucose-lowering medicinal products. The duration of the treatment ranged from 26 weeks to 78 weeks. The most frequently reported adverse reactions in clinical trials were gastrointestinal disorders, including nausea (very common), diarrhoea (very common) and vomiting (common).

1) and post-marketing reports in patients with type 2 diabetes mellitus. The frequencies of the adverse reactions (except diabetic retinopathy complications and dysaesthesia, see footnotes in Table 1) are based on a pool of the phase 3a trials excluding the cardiovascular outcomes trial.

The reactions are listed below by system organ class and absolute 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); very rare: (< 1/10 000) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 0 mmol/L or < 54 mg/dL. b) Diabetic retinopathy complications are a composite of retinal photocoagulation, treatment with intravitreal agents, vitreous haemorrhage and diabetes-related blindness (uncommon).

Frequency is based on the cardiovascular outcomes trial with subcutaneous semaglutide, but it cannot be excluded that the risk of diabetic retinopathy complications identified also applies to Rybelsus. c) Grouped term covering also adverse events related to hypersensitivity such as rash and urticaria.

d) From post-marketing reports. e) There were no imbalances of dysaesthesia events with Rybelsus 3 mg, 7 mg and 14 mg in phase 3a trials, however, events have been reported in the post- marketing experience. f) Grouped term covering PTs ‘intestinal obstruction’, ‘ileus’, ‘small intestinal obstruction’.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General Semaglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

2). There is no therapeutic experience in patients with congestive heart failure New York Heart Association (NYHA) class IV and semaglutide is therefore not recommended in these patients. There is no therapeutic experience with semaglutide in patients with bariatric surgery.

Aspiration in association with general anaesthesia or deep sedation Cases of pulmonary aspiration have been reported in patients receiving GLP-1 receptor agonists undergoing general anaesthesia or deep sedation. 8) should be considered prior to performing procedures with general anaesthesia or deep sedation.

Gastrointestinal effects and dehydration Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. 8). Patients treated with semaglutide should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion.

Acute pancreatitis Semaglutide has not been studied in patients with a history of pancreatitis, and should be used with caution in these patients. Acute pancreatitis has been reported in patients treated with GLP-1 receptor agonists.

This includes post-marketing reports of necrotising pancreatitis and reports with a fatal outcome. Patients should be informed of the symptoms of acute pancreatitis including persistent, severe abdominal pain. Patients should be advised to seek immediate medical attention if they occur.

If pancreatitis is suspected, semaglutide should be discontinued. If the diagnosis of pancreatitis is confirmed, semaglutide should not be restarted. 8). 8). 2). 8). Caution should be exercised when using semaglutide in patients with diabetic retinopathy.

1.