Wegovy · 4.8 Undesirable effects · 2

HOS-099647 · has-adverse-reaction-information · PDF-Seite 46

Summary of safety profile The most frequently reported adverse reactions were gastrointestinal disorders including nausea, diarrhoea, constipation, abdominal pain, dyspepsia and vomiting. These reactions were mainly seen in the dose-escalation period (see Description of selected adverse reactions). The safety profile of oral semaglutide was consistent with the safety profile of subcutaneous semaglutide. Tabulated list of adverse reactions Table 1 lists adverse reactions identified in clinical trials in adults and post-marketing reports. The frequencies are based, unless otherwise specified, on a pool of the subcutaneous semaglutide phase 3a trials (STEP 1-4), where 2650 adult patients were exposed to Wegovy. The duration of the trials was 68 weeks. The adverse reactions in OASIS 4 (204 adults with obesity or overweight with at least one weight-related comorbidity were exposed to oral semaglutide for 64 weeks) had similar frequencies to the subcutaneous phase 3a trials, except for dyspepsia which had a higher frequency category. Events not relevant for oral administration are omitted in the following overview. Adverse reactions are listed by MedDRA system organ class and frequency. Frequency categories 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 category, adverse reactions are presented in order of decreasing seriousness. Table 1 Adverse reactions MedDRA Very Uncommo Very system Common Rare Not known common n rare organ class Immune Anaphylacti system c reaction disorders Metabolism Hypoglycaemia and nutrition in patients with disorders type 2 diabetesa Nervous Headacheb Dizzinessb system Dysgeusiab,c disorders Dysaesthesiaa,c,g Eye disorders Diabetic Non- retinopathy in

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HOS-099641 · has-adverse-reaction-information · PDF-Seite 10

Summary of safety profile The most frequently reported adverse reactions were gastrointestinal disorders including nausea, diarrhoea, constipation, abdominal pain and vomiting. These reactions were mainly seen in the dose- escalation period (see Description of selected adverse reactions). Tabulated list of adverse reactions Table 3 lists adverse reactions identified in clinical trials in adults and post-marketing reports. The frequencies are based on a pool of four phase 3a trials (STEP 1-4), unless otherwise specified, where 2650 adult patients were exposed to Wegovy. The duration of the trials were 68 weeks. Adverse reactions are listed by MedDRA system organ class and frequency. Frequency categories 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 category, adverse reactions are presented in order of decreasing seriousness. Table 3 Adverse reactions MedDRA Very Uncommo system Common Rare Very Not known common n organ class rare Immune Anaphylacti system c reaction disorders Metabolism Hypoglycaemia and nutrition in patients with disorders type 2 diabetesa Nervous Headacheb Dizzinessb system Dysgeusiab,c disorders Dysaesthesiaa,c,f,g Eye disorders Diabetic Non- retinopathy in arteritic patients with anterior type 2 diabetesa ischaemic optic neuropath y

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HOS-099643 · has-contraindication-information · PDF-Seite 42

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

HOS-099637 · has-contraindication-information · PDF-Seite 6

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

HOS-099636 · has-indication-information · PDF-Seite 4

Adults Wegovy 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 • ≥30 kg/m2 (obesity), or • ≥27 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. For trial results with respect to cardiovascular risk reduction, obesity-related heart failure, and populations studied, see section 5.1. Adolescents (≥12 years of age) Wegovy is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adolescents aged 12 years and above with • obesity* and • body weight above 60 kg. Treatment with Wegovy 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 ≥95th percentile) as defined on gender- and age-specific BMI growth charts (CDC.gov) (see Table 1). Table 1 BMI cut-off points for obesity (≥95th percentile) by gender and age for paediatric patients aged 12 and older (CDC criteria) BMI (kg/m2) at 95th Percentile Age (years) Males Females 12 24.2 25.2 12.5 24.7 25.7 13 25.1 26.3 13.5 25.6 26.8 14 26.0 27.2 14.5 26.4 27.7 15 26.8 28.1 15.5 27.2 28.5 16 27.5 28.9 16.5 27.9 29.3 17 28.2 29.6 17.5 28.6 30.0 4

HOS-099642 · has-indication-information · PDF-Seite 41

Wegovy 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 • ≥ 30 kg/m2 (obesity), or • ≥ 27 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. For trial results with respect to populations studied, see section 5.1.

HOS-099645 · has-interaction-information · PDF-Seite 44

Semaglutide delays gastric emptying which may influence the absorption of other oral medicinal products. Effects of semaglutide on other medicinal products Thyroxine Total exposure (Area Under the Curve (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 and other coumarin derivatives 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, cases of decreased INR have been reported during concomitant use of acenocoumarol and semaglutide. 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. 44 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 (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 section 4.2). Paediatric population Interaction studies have only been performed in adults.

HOS-099639 · has-interaction-information · PDF-Seite 8

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. The effect of semaglutide 7.2 mg on the rate of gastric emptying has not been investigated. 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 AUC0-60min and Cmax were decreased by 27% and 23%, respectively, following concomitant use of semaglutide 1 mg. The total paracetamol exposure (AUC0-5h) 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. It 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. Cmax was not affected for any of the compounds. 8 Atorvastatin Semaglutide did not change the overall exposure of atorvastatin following a single dose administration of atorvastatin (40 mg). Atorvastatin Cmax was decreased by 38%. This was assessed not to be clinically relevant. Digoxin Semaglutide did not change the overall exposure or Cmax of digoxin following a single dose of digoxin (0.5 mg). Metformin Semaglutide did not change the overall exposure or Cmax of metformin following dosing of 500 mg twice daily over 3.5 days. Warfarin and other coumarin derivatives Semaglutide did not change overall exposure or Cmax 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 (INR) were not affected in a clinically relevant manner. However, cases of decreased INR have been reported during concomitant use of acenocoumarol and semaglutide. Upon initiation of

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HOS-099640 · has-pregnancy-information · PDF-Seite 9

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. 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 the newborns/infants 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. 9

HOS-099646 · has-pregnancy-information · PDF-Seite 45

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. 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 No measurable concentrations of semaglutide were found in breast milk of lactating women. Salcaprozate sodium was present in breast milk and some of its metabolites were excreted in breast milk at low concentrations. A risk to newborns/infants cannot be excluded. Wegovy 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.

HOS-099638 · has-warning-information · PDF-Seite 6

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. 6 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. Therefore, the increased risk of residual gastric content due to delayed gastric emptying (see section 4.8) 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. This should be considered when treating patients with impaired renal function, as nausea, vomiting, and diarrhoea may cause dehydration, which in rare cases can lead to a deterioration of renal function (see section 4.8). 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 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. Non-arteritic anterior ischaemic optic neuropathy (NAION) Data from epidemiological studies indicates an increased risk for non-arteritic anterior ischaemic optic neuropathy (NAION) during treatment with semaglutide. There is no identified time interval for when NAION may develop following treatment start. A sudden loss of vision should lead to ophthalmological examination and treatment with semaglutide should be discontinued if NAION is confirmed (see section 4.8). Patients with type 2 diabetes Semaglutide should 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 c

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HOS-099644 · has-warning-information · PDF-Seite 42

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. 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. Therefore, the increased risk of residual gastric content due to delayed gastric emptying (see section 4.8) 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. This should be considered when treating patients with impaired renal function, as nausea, vomiting, and 42 diarrhoea may cause dehydration, which in rare cases can lead to a deterioration of renal function (see section 4.8). 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 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. Non-arteritic anterior ischaemic optic neuropathy (NAION) Data from epidemiological studies indicates an increased risk for non-arteritic anterior ischaemic optic neuropathy (NAION) during treatment with semaglutide. There is no identified time interval for when NAION may develop following treatment start. A sudden loss of vision should lead to ophthalmological examination and treatment with semaglutide should be discontinued if NAION is confirmed (see section 4.8). Patients with type 2 diabetes Semaglutide should 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 co

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