Wegovy Solution for injection

Adults
Wegovy u00ae is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of
u2022 u226530 kg/m2 (obesity), or
u2022 u226527 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity e.g., dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease.
Adolescents (u2265 12 years)
Wegovy u00ae is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adolescents ages 12 years and above with
u2022 obesity* and
u2022 body weight above 60 kg.
Treatment with Wegovy u00ae should be discontinued and re-evaluated if adolescent patients have not reduced their BMI by at least 5 % after 12 weeks on the 2,4 mg or maximum tolerated dose.
*Obesity (BMI u2265 95th percentile) as defined on sex- and age-specific BMI growth charts (CDC.gov) (see Table 1).

Posology
Adults
The maintenance dose of semaglutide 2,4 mg once-weekly is reached by starting with a dose of 0,25 mg. To reduce the likelihood of gastrointestinal symptoms, the dose should be escalated over a 16-week period to a maintenance dose of 2,4 mg once weekly (see Table 2). In case of significant gastrointestinal symptoms, consider delaying dose escalation or lowering to the previous dose until symptoms have improved. Weekly doses higher than 2,4 mg are not recommended.
Table 2 Dose escalation schedule
Weekly dose
Week 1 u2013 4 0,25 mg
Week 5 u2013 8 0,5 mg
Week 9 u2013 12 1 mg
Week 13 u2013 16 1,7 mg
Maintenance dose 2,4 mg
Adolescents
For adolescents ages 12 years and above, the same dose escalation schedule as for adults should be applied (see Table 2). The dose should be increased until 2,4 mg (maintenance dose) or maximum tolerated dose has been reached. Weekly doses higher than 2,4 mg are not recommended.
Patients with type 2 diabetes
Wegovy u00ae should not be used in combination with other GLP-1 receptor agonist products. When initiating semaglutide in patients with type 2 diabetes, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia, see section 4.4.
Missed dose
If a dose is missed, it should be administered as soon as possible and within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule. If more doses are missed, reducing the starting dose for re-initiation should be considered.
Special populations
Elderly subjects (u2265 65 years old)
No dose adjustment is required based on age. Therapeutic experience in patients u2265 75 years of age is limited, and greater sensitivity of some older individuals cannot be excluded.
Patients with 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 for use in patients with severe renal impairment (eGFR < 30 mL/min/1,73 m2) including patients with end-stage renal disease (see sections 4.4, 4.8 and 5.2).
Patients with 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. Semaglutide is not recommended for use in patients with severe hepatic impairment and should be used cautiously in patients with mild or moderate hepatic impairment (see sections 4.4 and 5.2).
Paediatric population
No dose adjustment is required for adolescents ages 12 years and above. The safety and efficacy of semaglutide in children below 12 years of age have not been established.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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.
Dehydration
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 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 (see section 4.8). 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. In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.
Patients with type 2 diabetes
Semaglutide must not be used as a substitute for insulin in patients with type 2 diabetes. Semaglutide should not be used in combination with other GLP-1 receptor agonist products. It has not been evaluated and an increased risk of adverse reactions related to overdose is considered likely.
Hypoglycaemia in patients with type 2 diabetes
Insulin and sulfonylurea are known to cause 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 a GLP-1 receptor agonists. The addition of Wegovy u00ae in patients treated with insulin has not been evaluated.
Diabetic retinopathy in patients with type 2 diabetes
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Long-term glycaemic control decreases the risk of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for worsening and treated according to local clinical guidelines.
Populations not studied
The safety and efficacy of Wegovy u00ae have not been investigated in patients:
u2013 treated with other products for weight management,
u2013 with type 1 diabetes,
u2013 with severe renal impairment (see section 4.2),
u2013 with severe hepatic impairment (see section 4.2),
u2013 with congestive heart failure New York Heart Association (NYHA) class IV.
Use in these patients is not recommended. There is limited experience with Wegovy u00ae in patients:
u2013 aged 75 years or more (see section 4.2),
u2013 with mild or moderate hepatic impairment (see section 4.2),
u2013 with inflammatory bowel disease,
u2013 with diabetic gastroparesis.
Use with caution in these patients.
Sodium content
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially u2018sodium-freeu2019.

Semaglutide delays gastric emptying and could potentially influence the absorption of concomitantly administered oral medicinal products. No clinically relevant effect on the rate of gastric emptying was observed with semaglutide 2,4 mg probably due to a tolerance effect. Semaglutide should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption.
Paracetamol
Semaglutide delays the rate of gastric emptying as assessed by paracetamol pharmacokinetics during a standardised meal test. Paracetamol AUC 0-60min and C max were decreased by 27 % and 23 %, respectively, following concomitant use of semaglutide 1 mg. The total paracetamol exposure (AUC 0-5h) was not affected. No clinically relevant effect on paracetamol was observed with semaglutide. No dose adjustment of paracetamol is necessary when administered with semaglutide.
Oral contraceptives
Semaglutide is not anticipated to decrease the effectiveness of oral contraceptives as semaglutide did not change the overall exposure of ethinylestradiol and levonorgestrel to a clinically relevant degree, when an oral contraceptive combination medicinal product (0,03 mg ethinylestradiol/0,15 mg levonorgestrel) was co-administered with semaglutide. Exposure of ethinylestradiol was not affected; an increase of 20 % was observed for levonorgestrel exposure at steady state. C max was not affected for any of the compounds.
Atorvastatin
Semaglutide did not change the overall exposure of atorvastatin following a single dose administration of atorvastatin (40 mg). Atorvastatin C max was decreased by 38 %. This was assessed not to be clinically relevant.
Digoxin
Semaglutide did not change the overall exposure or C max of digoxin following a single dose of digoxin (0,5 mg).
Metformin
Semaglutide did not change the overall exposure or C max of metformin following dosing of 500 mg twice daily over 3,5 days.
Warfarin
Semaglutide did not change overall exposure or C max of R- and S-warfarin following a single dose of warfarin (25 mg), and the pharmacodynamic effects of warfarin as measured by the international normalised ratio 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 international normalised ratio (INR) is recommended.

Women of childbearing potential
Women of childbearing potential are recommended to use contraception when treated with semaglutide (see section 4.5).
Pregnancy
Studies in animals have shown reproductive toxicity (see section 5.3). There are limited data from the use of semaglutide in pregnant women. Therefore, semaglutide should not be used during pregnancy. Women of childbearing potential are recommended to use contraception when treated with semaglutide. 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 (see section 5.2).
Breast-feeding
In lactating rats, semaglutide was excreted in milk. A risk to a breast-fed child cannot be excluded. Semaglutide 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.

Semaglutide has no or negligible influence on the ability to drive or use machines. However, dizziness can be experienced mainly during the dose escalation period. Driving or use of machines should be done cautiously if dizziness occurs.
Patients with type 2 diabetes
If semaglutide is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines (see section 4.4).

Summary of safety profile
In four phase 3a trials, 2 650 patients were exposed to Wegovy u00ae. The duration of the trials were 68 weeks. The most frequently reported adverse reactions were gastrointestinal disorders including nausea, diarrhoea, constipation and vomiting.
Tabulated list of adverse reactions
Table 3 lists adverse reactions identified in phase 3a clinical trials. The frequencies are based on a pool of the phase 3a trials.
Adverse reactions associated with Wegovy u00ae are listed by body system and frequency. Frequency categories are defined as: Very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1 000 to < 1/100); rare (u2265 1/10 000 to < 1/1 000); very rare (< 1/10 000).

Overdose with semaglutide may be associated with gastrointestinal disorders which could lead to dehydration. In the event of overdose the patient should be observed for clinical signs and appropriate supportive treatment initiated.