Rybelsus

/ Novo Nordisk

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 maximum recommended single daily dose of semaglutide is 14 mg. Taking two 7 mg tablets to achieve the effect of a 14 mg dose has not been studied and is therefore not recommended.
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.
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.
Special populations
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 in children and adolescents below 18 years have not been established. No data are available.
See prescribing information for full details.

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
• in combination with other medicinal products for the treatment of diabetes.

Hypersensitivity to the active substance or to any of the excipients.

Traceability
In order to improve the traceability of biological medicinal products, the name of the administered product should be clearly recorded. It is recommended to record the batch number as well.
General
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.
Gastrointestinal effects
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. 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
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.
Hypoglycaemia
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.
Diabetic retinopathy
In patients with diabetic retinopathy treated with insulin and 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. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. Long-term glycaemic control decreases the risk of diabetic retinopathy.
Treatment response
Compliance with the dosing regimen is recommended for optimal effect of semaglutide. If the treatment response with semaglutide is lower than expected, the treating physician should be aware that the absorption of semaglutide is highly variable and may be minimal (2-4% of patients will not have any exposure), and that the absolute bioavailability of semaglutide is low.
Sodium content
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.
See prescribing information for full details.

Very common: Hypoglycaemia (when used with insulin or sulfonylurea), nausea, diarrhoea.
Common: Hypoglycaemia (when used with other oral antidiabetic products),
Decreased appetite, Dizziness, Headache, Diabetic retinopathy complications, vomiting, abdominal pain, abdominal distension, constipation, dyspepsia, gastritis, gastro-oesophageal reflux disease, flatulence, fatigue, increased lipase, increased amylase.

Semaglutide delays gastric emptying which may influence the absorption of other oral medicinal products.
Effects of semaglutide on other medicinal products
Thyroxine
Total exposure (AUC) of thyroxine (adjusted for endogenous levels) was increased by 33% following administration of a single dose of levothyroxine. Maximum exposure (Cmax) was unchanged. Monitoring of thyroid parameters should be considered when treating patients with semaglutide at the same time as levothyroxine.
Warfarin
Semaglutide did not change the AUC or Cmax of R- and S-warfarin following a single dose of warfarin, and the pharmacodynamic effects of warfarin as measured by the international normalised ratio (INR) were not affected in a clinically relevant manner. However, upon initiation of semaglutide treatment in patients on warfarin or other coumarin derivatives, frequent monitoring of INR is recommended.
Rosuvastatin
AUC of rosuvastatin was increased by 41% [90% CI: 24; 60] when co-administered with semaglutide. Based on the wide therapeutic index of rosuvastatin the magnitude of changes in the exposure is not considered clinically relevant.
Digoxin, oral contraceptives, metformin, furosemide
No clinically relevant change in AUC or Cmax of digoxin, oral contraceptives (containing ethinylestradiol and levonorgestrel), metformin or furosemide was observed when concurrently administered with semaglutide.
Interactions with medicinal products with very low bioavailability (F: 1%) have not been evaluated.
Effects of other medicinal products on semaglutide
Omeprazole
No clinically relevant change in AUC or Cmax of semaglutide was observed when taken with omeprazole.
In a trial investigating the pharmacokinetics of semaglutide co-administered with five other tablets, the AUC of semaglutide decreased by 34% and Cmax by 32%. This suggests that the presence of multiple tablets in the stomach influences the absorption of semaglutide if co-administered at the same time. After administering semaglutide, the patients should wait 30 minutes before taking other oral medicinal products.
See prescribing information for full details.

Women of childbearing potential
Women of childbearing potential are recommended to use contraception when treated with semaglutide.
Pregnancy
Studies in animals have shown reproductive toxicity. There are limited data from the use of semaglutide in pregnant women. Therefore, semaglutide should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, semaglutide should be discontinued. Semaglutide should be discontinued at least 2 months before a planned pregnancy due to the long half-life.
Breast-feeding
In lactating rats, semaglutide, salcaprozate sodium and/or its metabolites were excreted in milk. As a risk to a breast-fed child cannot be excluded, Rybelsus should not be used during breast-feeding.
Fertility
The effect of semaglutide on fertility in humans is unknown. Semaglutide did not affect male fertility in rats. In female rats, an increase in oestrous length and a small reduction in number of ovulations were observed at doses associated with maternal body weight loss.

Effects of overdose with semaglutide in clinical studies may be associated with gastrointestinal disorders. In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. A prolonged period of observation and treatment of the symptoms may be necessary, taking into account the long half-life of semaglutide of approximately 1 week. There is no specific antidote for overdose with semaglutide.

When it is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.