Prescribing information

Rybelsus^®
Semaglutide tablets
Rybelsus 3 mg tablet
Rybelsus 7 mg tablet
Rybelsus 14 mg tablet
Consult Summary of Product Characteristics before prescribing.
Presentation: Rybelsus^® 3 mg, 7 mg and 14 mg tablets for once‑daily oral use. Each tablet contains 3, 7 or 14 mg semaglutide and, regardless of semaglutide strength, 23 mg sodium. Uses: Rybelsus^® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise as monotherapy when metformin is considered inappropriate due to intolerance or contraindications, or in combination with other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see the full Summary of Product Characteristics. Dosage and Administration: The starting dose of Rybelsus^® 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. If a dose is missed, the missed dose should be skipped, and the next dose should be taken the following day. Rybelsus^® should be taken on an empty stomach at any time of the day. Rybelsus^® should be swallowed whole with a sip of water (up to half of glass of water equivalent to 120 ml). The tablet should not be split, crushed or chewed, as it is not known if this impacts absorption of semaglutide. Patients should wait at least 30 minutes before eating or drinking or taking other oral medicinal products. Waiting less than 30 minutes decreases the absorption of semaglutide. 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. When semaglutide is used in combination with a sulfonylurea or with insulin, a reduction in the dose of sulfonylurea or insulin may be considered to reduce the risk of hypoglycaemia. Elderly: No dose adjustment is required based on age. Therapeutic experience in patients ≥75 years of age is limited. Renal impairment: No dose adjustment is required for patients with mild, moderate or severe renal impairment. Experience with the use of semaglutide in patients with severe renal impairment is limited. Semaglutide is not recommended in patients with end-stage renal disease. 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. Caution should be exercised when treating these patients with semaglutide. Paediatric population: The safety and efficacy of Rybelsus^® in children and adolescents below 18 years have not been established. No data are available. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use: Semaglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Diabetic ketoacidosis has been reported in insulin-dependent patients whom had rapid discontinuation or dose reduction of insulin when treatment with a GLP-1 receptor agonist is started. 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. Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions that can cause dehydration, which in rare cases can lead to a deterioration of renal function. Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, semaglutide should be discontinued; if confirmed, semaglutide should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Patients treated with semaglutide in combination with a sulfonylurea or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia can be lowered by reducing the dose of sulfonylurea or insulin when initiating treatment with semaglutide. In patients with diabetic retinopathy treated with insulin and subcutaneous (s.c.) semaglutide, an increased risk of developing diabetic retinopathy complications has been observed, a risk that cannot be excluded for orally administered semaglutide. Caution should be exercised when using semaglutide in patients with diabetic retinopathy. These patients should be monitored closely and treated according to clinical guidelines. Compliance with the dosing regimen is recommended for optimal effect of semaglutide. This medicinal product contains 23 mg sodium per tablet, equivalent to 1% of the WHO recommended maximum daily intake of 2 g sodium for an adult. Interactions: Semaglutide delays gastric emptying which may influence the absorption of other oral medicinal products. No clinically relevant change in total or maximum exposure of digoxin, oral contraceptives (containing ethinylestradiol and levonorgestrel), metformin, furosemide, rosuvastatin, omeprazole or warfarin was observed when concurrently administered with semaglutide. However, upon initiation of semaglutide treatment in patients on warfarin or other coumarin derivatives, frequent monitoring of international normalised ratio (INR) is recommended. Total exposure of thyroxine increased by 33% following administration of a single dose of levothyroxine. Maximum exposure was unchanged. Monitoring of thyroid parameters should be considered when treating patients with semaglutide at the same time as levothyroxine. For further details of these interaction studies, please see the Summary of Product Characteristics. Pregnancy and lactation: Rybelsus^® should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, Rybelsus^® should be discontinued. Rybelsus^® should not be used during breast-feeding. Driving or using machines: When Rybelsus^® is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines. Undesirable Effects: The most frequently reported adverse reactions in clinical trials were gastrointestinal disorders, including nausea, diarrhoea, and vomiting. Adverse reactions by system organ class and absolute frequencies identified in the phase 3a trials listed here as Very common (≥1/10): Hypoglycaemia when used with insulin or sulfonylurea, nausea, diarrhoea; Common (≥1/100 to <1/10): Hypoglycaemia when used with other oral antidiabetic products, decreased appetite, diabetic retinopathy complications, vomiting, abdominal pain, abdominal distension, constipation, dyspepsia, gastritis, gastro-oesophageal reflux disease, flatulence, fatigue, increased lipase, increased amylase; Uncommon (≥1/1,000 to <1/100): increased heart rate, eructation, cholelithiasis, weight decreased, hypersensitivity; Rare (≥1/10,000 to <1/1,000): anaphylactic reaction, acute pancreatitis. For further details of these side-effects, please see the Summary of Product Characteristics, which is available at www.ema.europa.eu/en/medicines/human/EPAR/rybelsus. Marketing authorisation number: EU/1/20/1430/001-013. Legal category: Prescription-only medicine (POM). Marketing authorisation holder: Novo Nordisk A/S Novo Allé DK-2880 Bagsværd Denmark. Date of review of abbreviated prescribing information: 04 2022. Summary of Product Characteristics can be obtained from Novo Nordisk A/S.