Rybelsus

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 3 mg tablets 
Rybelsus 7 mg tablets 
Rybelsus 14 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Rybelsus 3 mg tablets 
 
Each tablet contains 3 mg semaglutide*. 
 
Rybelsus 7 mg tablets 
 
Each tablet contains 7 mg semaglutide*. 
 
Rybelsus 14 mg tablets 
 
Each tablet contains 14 mg semaglutide*. 
 
*human glucagon-like peptide-1 (GLP-1) analogue produced in Saccharomyces cerevisiae cells by 
recombinant DNA technology. 
 
Excipient with known effect 
 
Each tablet, regardless of semaglutide strength, contains 23 mg sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet 
 
Rybelsus 3 mg tablets 
 
White to light yellow, oval shaped tablet (7.5 mm x 13.5 mm) debossed with ‘3’ on one side and 
‘novo’ on the other side. 
 
Rybelsus 7 mg tablets 
 
White to light yellow, oval shaped tablet (7.5 mm x 13.5 mm) debossed with ‘7’ on one side and 
‘novo’ on the other side. 
 
Rybelsus 14 mg tablets 
 
White to light yellow, oval shaped tablet (7.5 mm x 13.5 mm) debossed with ‘14’ on one side and 
‘novo’ on the other side. 
 
 
4. CLINICAL PARTICULARS 



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4.1 Therapeutic indications 
 
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 
• 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 sections 4.4, 4.5 and 5.1. 
 
4.2 Posology and method of administration 
 
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 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. 
 
For information on switching between oral and subcutaneous (s.c.) semaglutide, see section 5.2. 
 
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. 
 
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 (see section 4.4 and 
4.8). 
 
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.  
 
Special populations 
 
Elderly 
No dose adjustment is required based on age. Therapeutic experience in patients ≥75 years of age is 
limited (see section 5.2). 
 
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 (see section 5.2). 
 
Hepatic impairment 



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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 (see section 5.2). 
 
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.  
 
– This medicinal product should be taken on an empty stomach at any time of the day. 
– 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 or drinking or taking other oral medicinal 
products. Waiting less than 30 minutes decreases the absorption of semaglutide (see sections 4.5 
and 5.2). 

 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
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. 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 (see section 4.2). 
 
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. 
 
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 (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. 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. 
 



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Hypoglycaemia 
 
Patients treated with semaglutide in combination with a sulfonylurea or insulin may have an increased 
risk of hypoglycaemia (see section 4.8). The risk of hypoglycaemia can be lowered by reducing the 
dose of sulfonylurea or insulin when initiating treatment with semaglutide (see section 4.2). 
 
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 (see data in section 4.8). 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.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 



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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 section 4.2). 
 
4.6 Fertility, pregnancy and lactation 
 
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 (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, 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 (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Semaglutide has no or negligible influence on the ability to drive or use machines. 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 (see section 4.4). 
 
4.8 Undesirable effects 
 
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). 
 
Tabulated list of adverse reactions 
 



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Table 1 lists adverse reactions identified in all phase 3a trials in patients with type 2 diabetes mellitus 
(further described in section 5.1). The frequencies of the adverse reactions 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) and very rare: (<1/10,000). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
Table 1 Adverse reactions from controlled phase 3a trials 

MedDRA 
system organ 
class 

Very common Common Uncommon Rare 

Immunesystem 
disorders  

   Anaphylactic 
reaction 

Metabolism 
and nutrition 
disorders  

Hypoglycaemia 
when used with 
insulin or 
sulfonylureaa 

Hypoglycaemia 
when used with 
other oral 
antidiabetic 
productsa 
Decreased 
appetite 

  

Eye disorders  Diabetic 
retinopathy 
complicationsb 

  

Cardiac 
disorders  

  Increased heart 
rate  

 

Gastrointestinal 
disorders  

Nausea 
Diarrhoea 

Vomiting 
Abdominal pain 
Abdominal 
distension 
Constipation 
Dyspepsia 
Gastritis 
Gastro-
oesophageal 
reflux disease 
Flatulence 

Eructation Acute 
pancreatitis 

Hepatobiliary 
disorders  

  Cholelithiasis  

General 
disorders and 
administration 
site conditions  

 Fatigue    

Investigations  Increased lipase 
Increased 
amylase 

Weight 
decreased 

 

a) Hypoglycaemia defined as blood glucose <3.0 mmol/L or <54 mg/dL 
b) Diabetic retinopathy complications is 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 s.c. 
semaglutide, but it cannot be excluded that the risk of diabetic retinopathy complications identified also applies to Rybelsus. 
 
Description of selected adverse reactions 
 
Hypoglycaemia 
Severe hypoglycaemia was primarily observed when semaglutide was used with a sulfonylurea 
(<0.1% of subjects, <0.001 events/patient year) or insulin (1.1% of subjects, 0.013 events/patient 



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year). Few episodes (0.1% of subjects, 0.001 events/patient year) were observed with semaglutide in 
combination with oral antidiabetics other than sulfonylurea. 
 
Gastrointestinal adverse reactions 
Nausea occurred in 15%, diarrhoea in 10%, and vomiting in 7% of patients when treated with 
semaglutide. Most events were mild to moderate in severity and of short duration. The events led to 
treatment discontinuation in 4% of subjects. The events were most frequently reported during the first 
months on treatment. 
 
Acute pancreatitis confirmed by adjudication has been reported in phase 3a trials, semaglutide 
(<0.1%) and comparator (0.2%). In the cardiovascular outcomes trial the frequency of acute 
pancreatitis confirmed by adjudication was 0.1% for semaglutide and 0.2% for placebo (see section 
4.4.) 
 
Diabetic retinopathy complications 
A 2-year clinical trial with s.c. semaglutide investigated 3,297 patients with type 2 diabetes, with high 
cardiovascular risk, long duration of diabetes and poorly controlled blood glucose. In this trial, 
adjudicated events of diabetic retinopathy complications occurred in more patients treated with s.c. 
semaglutide (3.0%) compared to placebo (1.8%). This was observed in insulin-treated patients with 
known diabetic retinopathy. The treatment difference appeared early and persisted throughout the trial. 
Systematic evaluation of diabetic retinopathy complication was only performed in the cardiovascular 
outcomes trial with s.c. semaglutide. In clinical trials with Rybelsus of up to 18 months duration 
involving 6,352 patients with type 2 diabetes, adverse events related to diabetic retinopathy were 
reported in similar proportions in subjects treated with semaglutide (4.2%) and comparators (3.8%). 
 
Immunogenicity 
Consistent with the potential immunogenic properties of medicinal products containing proteins or 
peptides, patients may develop antibodies following treatment with semaglutide. The proportion of 
subjects tested positive for anti-semaglutide antibodies at any time point after baseline was low (0.5%) 
and no subjects had neutralising anti-semaglutide antibodies or anti-semaglutide antibodies with 
neutralising effect on endogenous GLP-1 at end-of-trial. 
 
Heart rate increase 
Increased heart rate has been observed with GLP-1 receptor agonists. In the phase 3a trials, mean 
changes of 0 to 4 beats per minute (bpm) from a baseline of 69 to 76 were observed in patients treated 
with Rybelsus.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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 (see section 5.2). There is no specific antidote for overdose with semaglutide.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Pharmacotherapeutic group: Drugs used in diabetes, Glucagon-like peptide-1 (GLP-1) analogues, 
ATC code: A10BJ06 
 
Mechanism of action 
 
Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as 
a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for 
native GLP-1. 
 
GLP-1 is a physiological hormone that has multiple actions in glucose and appetite regulation, and in 
the cardiovascular system. The glucose and appetite effects are specifically mediated via GLP-1 
receptors in the pancreas and the brain. 
  
Semaglutide reduces blood glucose in a glucose-dependent manner by stimulating insulin secretion 
and lowering glucagon secretion when blood glucose is high. The mechanism of blood glucose 
lowering also involves a minor delay in gastric emptying in the early postprandial phase. During 
hypoglycaemia, semaglutide diminishes insulin secretion and does not impair glucagon secretion. The 
mechanism of semaglutide is independent of the route of administration. 
 
Semaglutide reduces body weight and body fat mass through lowered energy intake, involving an 
overall reduced appetite. In addition, semaglutide reduces the preference for high fat foods. 
 
GLP-1 receptors are expressed in the heart, vasculature, immune system and kidneys. Semaglutide has 
a beneficial effect on plasma lipids, lowers systolic blood pressure and reduces inflammation in 
clinical studies. In animal studies, semaglutide attenuates the development of atherosclerosis by 
preventing aortic plaque progression and reducing inflammation in the plaque.  
 
Pharmacodynamic effects 
 
The pharmacodynamic evaluations described below were performed with orally administered 
semaglutide after 12 weeks of treatment. 
 
Fasting and postprandial glucose 
Semaglutide reduces fasting and postprandial glucose concentrations. In patients with type 2 diabetes, 
treatment with semaglutide resulted in a relative reduction compared to placebo of 22% [13; 30] for 
fasting glucose and 29% [19; 37] for postprandial glucose. 
 
Glucagon secretion 
Semaglutide lowers the postprandial glucagon concentrations. In patients with type 2 diabetes, 
semaglutide resulted in the following relative reductions in glucagon compared to placebo: 
postprandial glucagon response of 29% [15; 41]. 
 
Gastric emptying 
Semaglutide causes a minor delay in early postprandial gastric emptying, with paracetamol exposure 
(AUC0-1h) 31% [13; 46] lower in the first hour after the meal, thereby reducing the rate at which 
glucose appears in the circulation postprandially. 
 
Fasting and postprandial lipids 
Semaglutide compared to placebo lowered fasting triglyceride and very-low-density lipoproteins 
(VLDL) cholesterol concentrations by 19% [8; 28] and 20% [5; 33], respectively. The postprandial 
triglyceride and VLDL cholesterol response to a high fat meal was reduced by 24% [9; 36] and 21% 
[7; 32], respectively. ApoB48 was reduced both in fasting and postprandial state by 25% [2; 42] and 
30% [15; 43], respectively. 
 
Clinical efficacy and safety 
 



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The efficacy and safety of Rybelsus have been evaluated in eight global randomised controlled phase 
3a trials. In seven trials, the primary objective was the assessment of the glycaemic efficacy; in one 
trial, the primary objective was the assessment of cardiovascular outcomes. 
 
The trials included 8,842 randomised patients with type 2 diabetes (5,169 treated with semaglutide), 
including 1,165 patients with moderate renal impairment. Patients had an average age of 61 years 
(range 18 to 92 years), with 40% of patients ≥ 65 years of age and 8% ≥ 75 years of age. The efficacy 
of semaglutide was compared with placebo or active controls (sitagliptin, empagliflozin and 
liraglutide).  
 
The efficacy of semaglutide was not impacted by baseline age, gender, race, ethnicity, body weight, 
BMI, diabetes duration, upper gastrointestinal disease and level of renal function. 
 
PIONEER 1 – Monotherapy 
In a 26-week double-blind trial, 703 patients with type 2 diabetes inadequately controlled with diet and 
exercise were randomised to semaglutide 3 mg, semaglutide 7 mg, semaglutide 14 mg or placebo once 
daily. 
 
Table 2 Results of a 26-week monotherapy trial comparing semaglutide with placebo 
(PIONEER 1) 

 Semaglutide 
7 mg 

Semaglutide 
14 mg 

Placebo 

Full analysis set (N) 175 175 178 
HbA1c (%)    

Baseline 8.0 8.0 7.9 
Change from baseline1 −1.2 −1.4 −0.3 
Difference from placebo1 [95% CI] −0.9 [−1.1; −0.6]* −1.1 [−1.3; −0.9]* - 

Patients (%) achieving HbA1c <7.0% 69§ 77§ 31 
FPG (mmol/L)    

Baseline 9.0 8.8 8.9 
Change from baseline1 −1.5 −1.8 −0.2 
Difference from placebo1 [95% CI] −1.4 [−1.9; −0.8]§ −1.6 [−2.1; −1.2]§ - 

Body weight (kg)    
Baseline 89.0 88.1 88.6 
Change from baseline1  −2.3 −3.7 −1.4 
Difference from placebo1 [95% CI] −0.9 [−1.9; 0.1] −2.3 [−3.1; −1.5]* - 

1 Irrespective of treatment discontinuation or initiation of rescue medication (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. 
 
PIONEER 2 – Semaglutide vs. empagliflozin, both in combination with metformin 
In a 52-week open-label trial, 822 patients with type 2 diabetes were randomised to semaglutide 14 mg 
once daily or empagliflozin 25 mg once daily, both in combination with metformin. 
 
Table 3 Results of a 52-week trial comparing semaglutide with empagliflozin (PIONEER 2) 

 Semaglutide 
14 mg 

Empagliflozin 
25 mg 

Full analysis set (N) 411 410 
Week 26   

HbA1c (%)    
Baseline 8.1 8.1 
Change from baseline1 −1.3 −0.9 
Difference from empagliflozin1 [95% CI] −0.4 [−0.6; −0.3]* - 

Patients (%) achieving HbA1c <7.0% 67§ 40 



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FPG (mmol/L)    
Baseline 9.5 9.7 
Change from baseline1 −2.0 −2.0 
Difference from empagliflozin1 [95% CI] 0.0 [−0.2; 0.3] - 

Body weight (kg)    
Baseline 91.9 91.3 
Change from baseline1 −3.8 −3.7 
Difference from empagliflozin1 [95% CI]  −0.1 [−0.7; 0.5] - 

Week 52   
HbA1c (%)   

Change from baseline1 −1.3 −0.9 
Difference from empagliflozin1 [95% CI] −0.4 [−0.5; −0.3]§ - 

Patients (%) achieving HbA1c <7.0% 66§ 43 
Body weight (kg)   

Change from baseline1 −3.8 −3.6 
Difference from empagliflozin1 [95% CI]  −0.2 [−0.9; 0.5] - 

1 Irrespective of treatment discontinuation or initiaton of rescue medicaton (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. 
 
PIONEER 3 – Semaglutide vs. sitagliptin, both in combination with metformin or metformin with 
sulfonylurea 
In a 78-week, double-blind, double-dummy trial, 1,864 patients with type 2 diabetes were randomised 
to semaglutide 3 mg, semaglutide 7 mg, semaglutide 14 mg or sitagliptin 100 mg once daily, all in 
combination with metformin alone or metformin and sulfonylurea. Reductions in HbA1c and body 
weight were sustained throughout the trial duration of 78 weeks. 
 
Table 4 Results of a 78-week trial comparing semaglutide with sitagliptin (PIONEER 3) 

 Semaglutide 
7 mg 

Semaglutide 
14 mg 

Sitagliptin 
100 mg 

Full analysis set (N) 465 465 467 
Week 26    

HbA1c (%)     
Baseline 8.4 8.3 8.3 
Change from baseline1 −1.0  −1.3 −0.8 
Difference from sitagliptin1 [95% CI] −0.3 [−0.4; −0.1]* −0.5 [−0.6; −0.4]* - 

Patients (%) achieving HbA1c <7.0% 44§ 56§ 32 
FPG (mmol/L)     

Baseline 9.4 9.3 9.5 
Change from baseline1 −1.2 −1.7 −0.9 
Difference from sitagliptin1 [95% CI] −0.3 [−0.6; 0.0]§ −0.8 [−1.1; −0.5]§ - 

Body weight (kg)     
Baseline 91.3 91.2 90.9 
Change from baseline1 −2.2 −3.1 −0.6 
Difference from sitagliptin1 [95% CI]  −1.6 [−2.0; −1.1]* −2.5 [−3.0; −2.0]* - 

Week 78    
HbA1c (%)    

Change from baseline1 −0.8 −1.1 −0.7 
Difference from sitagliptin1 [95% CI] −0.1 [−0.3; 0.0] −0.4 [−0.6; −0.3]§ - 

Patients (%) achieving HbA1c <7.0% 39§ 45§ 29 
Body weight (kg)    

Change from baseline1  −2.7 −3.2 −1.0 
Difference from sitagliptin1 [95% CI] −1.7 [−2.3; −1.0]§ −2.1 [−2.8; −1.5]§ - 



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1 Irrespective of treatment discontinuation or initiation of rescue medication (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. 
 
PIONEER 4 – Semaglutide vs. liraglutide and placebo, all in combination with metformin or 
metformin with an SGLT2 inhibitor 
In a 52-week double-blind, double-dummy trial, 711 patients with type 2 diabetes were randomised to 
semaglutide 14 mg, liraglutide 1.8 mg s.c. injection or placebo once daily, all in combination with 
metformin or metformin and an SGLT2 inhibitor. 
 
Table 5 Results of a 52-week trial comparing semaglutide with liraglutide and placebo 
(PIONEER 4) 

 Semaglutide 
14 mg 

Liraglutide 
1.8 mg 

Placebo 

Full analysis set (N) 285 284 142 
Week 26    

HbA1c (%)    
Baseline 8.0 8.0 7.9 
Change from baseline1 −1.2 −1.1 −0.2 
Difference from liraglutide1 [95% CI] −0.1 [−0.3; 0.0]  - - 
Difference from placebo1 [95% CI] −1.1 [−1.2; −0.9]* - - 

Patients (%) achieving HbA1c <7.0% 68§,a 62 14 
FPG (mmol/L)    

Baseline 9.3 9.3 9.2 
Change from baseline1 −2.0 −1.9 −0.4 
Difference from liraglutide1 [95% CI] −0.1 [−0.4; 0.1]  - - 
Difference from placebo1 [95% CI] −1.6 [−2.0; −1.3]§ - - 

Body weight (kg)    
Baseline 92.9 95.5 93.2 
Change from baseline1 −4.4 −3.1 −0.5 
Difference from liraglutide1 [95% CI] −1.2 [−1.9; −0.6]*  - - 
Difference from placebo1 [95% CI] −3.8 [−4.7; −3.0]* - - 

Week 52    
HbA1c (%)    

Change from baseline1 −1.2 −0.9 −0.2 
Difference from liraglutide1 [95% CI] −0.3 [−0.5; −0.1]§ - - 
Difference from placebo1 [95% CI] −1.0 [−1.2; −0.8]§ - - 

Patients (%) achieving HbA1c <7.0% 61§,a 55 15 
Body weight (kg)    

Change from baseline1 −4.3 −3.0 −1.0 
Difference from liraglutide1 [95% CI] −1.3 [−2.1; −0.5]§ - - 
Difference from placebo1 [95% CI] −3.3 [−4.3; −2.4]§ - - 

1 Irrespective of treatment discontinuation or initiation of rescue medication (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. a vs placebo. 
 
PIONEER 5 – Semaglutide vs. placebo, both in combination with basal insulin alone, metformin and 
basal insulin or metformin and/or sulfonylurea, in patients with moderate renal impairment 
In a 26-week double-blind trial, 324 patients with type 2 diabetes and moderate renal impairment 
(eGFR 30-59 ml/min/1.73 m2) were randomised to semaglutide 14 mg or placebo once daily. Trial 
product was added to the patient’s stable pre-trial antidiabetic regimen. 
 
Table 6 Results of a 26-week trial comparing semaglutide with placebo in patients with type 2 
diabetes and moderate renal impairment (PIONEER 5) 

 Semaglutide 
14 mg 

Placebo 



13 

Full analysis set (N) 163 161 
HbA1c (%)   

Baseline 8.0 7.9 
Change from baseline1 −1.0 −0.2 
Difference from placebo1 [95% CI] −0.8 [−1.0; −0.6]* - 

Patients (%) achieving HbA1c <7.0% 58§ 23 
FPG (mmol/L)   

Baseline 9.1 9.1 
Change from baseline1 −1.5 −0.4 
Difference from placebo1 [95% CI] −1.2 [−1.7; −0.6]§ - 

Body weight (kg)   
Baseline 91.3 90.4 
Change from baseline1 −3.4 −0.9 
Difference from placebo1 [95% CI] −2.5 [−3.2; −1.8]* - 

1 Irrespective of treatment discontinuation or initiation of rescue medication (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. 
 
PIONEER 7 – Semaglutide vs. sitagliptin, both in combination with metformin, SGLT2 inhibitors, 
sulfonylurea or thiazolidinediones. Flexible-dose-adjustment trial  
In a 52-week open-label trial, 504 patients with type 2 diabetes were randomised to semaglutide 
(flexible dose adjustment of 3 mg, 7 mg, and 14 mg once daily) or sitagliptin 100 mg once daily, all in 
combination with 1-2 oral glucose-lowering medicinal products (metformin, SGLT2 inhibitors, 
sulfonylurea or thiazolidinediones). The dose of semaglutide was adjusted every 8 weeks based on 
patient’s glycaemic response and tolerability. The sitagliptin 100 mg dose was fixed. The efficacy and 
safety of semaglutide were evaluated at week 52. 
 
At week 52, the proportion of patients on treatment with semaglutide 3 mg, 7 mg and 14 mg was 
approximately 10%, 30% and 60%, respectively. 
 
Table 7 Results of a 52-week flexible-dose-adjustment trial comparing semaglutide with 
sitagliptin (PIONEER 7) 

 Semaglutide 
Flexible dose 

Sitagliptin 
100 mg 

Full analysis set (N) 253 251 
HbA1c (%)   

Baseline 8.3 8.3 
Patients (%) achieving HbA1c <7.0%1 58* 25 

Body weight (kg)   
Baseline 88.9 88.4 
Change from baseline1 −2.6 −0.7 
Difference from sitagliptin1 [95% CI] −1.9 [−2.6; −1.2]* - 

1 Irrespective of treatment discontinuation (16.6% of the patients with semaglutide flexible dose and 9.2% with sitagliptin, 
where 8.7% and 4.0%, respectively, were due to AEs) or initiation of rescue medication (pattern mixture model using 
multiple imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity (for ‘Patients achieving 
HbA1c <7.0%’, the p-value is for the odds ratio). 
 
PIONEER 8 – Semaglutide vs. placebo, both in combination with insulin with or without metformin 
In a 52-week double-blind trial, 731 patients with type 2 diabetes inadequately controlled on insulin 
(basal, basal/bolus or premixed) with or without metformin were randomised to semaglutide 3 mg, 
semaglutide 7 mg, semaglutide 14 mg or placebo once daily. 
 
Table 8 Results of a 52-week trial comparing semaglutide with placebo in combination with 
insulin (PIONEER 8) 



14 

 Semaglutide 
7 mg 

Semaglutide 
14 mg 

Placebo 

Full analysis set (N) 182 181 184 
Week 26 (insulin dose capped to baseline 
level) 

   

HbA1c (%)     
Baseline 8.2 8.2 8.2 
Change from baseline1 −0.9 −1.3 −0.1 
Difference from placebo1 [95% CI] −0.9 [−1.1; −0.7]* −1.2 [−1.4; −1.0]* - 

Patients (%) achieving HbA1c <7.0% 43§ 58§ 7 
FPG (mmol/L)     

Baseline 8.5 8.3 8.3 
Change from baseline1 −1.1 −1.3 0.3 
Difference from placebo1 [95% CI] −1.4 [−1.9; −0.8]§ −1.6 [−2.2; −1.1]§ - 

Body weight (kg)     
Baseline 87.1 84.6 86.0 
Change from baseline1 −2.4 −3.7 −0.4 
Difference from placebo1 [95% CI] −2.0 [−3.0; −1.0]* −3.3 [−4.2; −2.3]* - 

Week 52 (uncapped insulin dose)+    
HbA1c (%)    

Change from baseline1 −0.8 −1.2 -0.2 
Difference from placebo1 [95% CI] −0.6 [−0.8; −0.4]§ −0.9 [−1.1; −0.7]§ - 

Patients (%) achieving HbA1c <7.0% 40§ 54§ 9 
Body weight (kg)    

Change from baseline1 −2.0 −3.7 0.5 
Difference from placebo1 [95% CI] −2.5 [−3.6; −1.4]§ −4.3 [−5.3; −3.2]§ - 

1 Irrespective of treatment discontinuation or initiation of rescue medication (pattern mixture model using multiple 
imputation). * p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity. § p<0.05, not controlled for 
multiplicity; for ‘Patients achieving HbA1c <7.0%’, the p-value is for the odds ratio. + The total daily insulin dose was 
statistically significantly lower with semaglutide than with placebo at week 52. 
 
Cardiovascular evaluation 
 
In a double-blind trial (PIONEER 6), 3,183 patients with type 2 diabetes at high cardiovascular risk 
were randomised to Rybelsus 14 mg once daily or placebo in addition to standard-of-care. The median 
observation period was 16 months.  
 
The primary endpoint was time from randomisation to first occurrence of a major adverse 
cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction or non-fatal 
stroke. 
 
Patients eligible to enter the trial were: 50 years of age or older and with established cardiovascular 
disease and/or chronic kidney disease, or 60 years of age or older and with cardiovascular risk factors 
only. In total, 1,797 patients (56.5%) had established cardiovascular disease without chronic kidney 
disease, 354 (11.1%) had chronic kidney disease only and 544 (17.1%) had both cardiovascular 
disease and kidney disease. 488 patients (15.3%) had cardiovascular risk factors only. The mean age at 
baseline was 66 years, and 68% of the patients were men. The mean duration of diabetes was 14.9 
years and the mean BMI was 32.3 kg/m2. Medical history included stroke (11.7%) and myocardial 
infarction (36.1%). 
 
The total number of first MACE was 137: 61 (3.8%) with semaglutide and 76 (4.8%) with placebo. 
The analysis of time to first MACE resulted in a HR of 0.79 [0.57; 1.11]95% CI. 
 



15 

 

Time from randomisation (week) 

Number of subjects at risk 

Pr
op

or
tio

n 
of

 su
bj

ec
ts 

(%
) 

Rybelsus 
Placebo 

Rybelsus Placebo 

HR: 0.79 
95% CI 0.57; 1.11 

 
Cumulative incidence plot of primary outcome (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) with 
non-cardiovascular death as competing risk.  
Abbreviations: CI: Confidence interval, HR: Hazard ratio 
Figure 1 Cumulative incidence of first occurrence of MACE in PIONEER 6 
 
The treatment effect for the primary composite endpoint and its components in the PIONEER 6 trial is 
shown in Figure 2. 
 
 

Primary endpoint – MACE 

Components of MACE 

FAS 

Cardiovascular death 

Non-fatal stroke 

Non-fatal myocardial infarction 

Other secondary endpoints 

All cause death 

Hazard Ratio 
(95% CI) 

Rybelsus 
N (%) 

Placebo 
N (%) 

Favours Rybelsus Favours placebo 

0.2 5 1 

0.51  
(0.31-0.84) 

23 
(1.4) 

45 
(2.8) 

1.18  
(0.73-1.90) 

37 
(2.3) 

31 
(1.9) 

0.74  
(0.35-1.57) 

12 
(0.8) 

16 
(1.0) 

0.49  
(0.27-0.92) 

15 
(0.9) 

30 
(1.9) 

0.79  
(0.57-1.11) 

61 
(3.8) 

76 
(4.8) 

1591 
(100) 

1592 
(100) 

 
Figure 2 Treatment effect for the primary composite endpoint, its components and all cause death 
(PIONEER 6) 
 
Body weight 
 



16 

By end-of-treatment, 27-45% of the patients had achieved a weight loss of ≥5% and 6-16% had 
achieved a weight loss of ≥10% with semaglutide, compared with 12-39% and 2-8%, respectively, 
with the active comparators.  
 
Blood pressure 
 
Treatment with semaglutide had reduced systolic blood pressure by 2-7 mmHg. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Rybelsus in one or more subsets of the paediatric population in type 2 diabetes (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Orally administered semaglutide has a low absolute bioavailability and a variable absorption. Daily 
administration according to the recommended posology in combination with a long half-life reduces 
day-to-day fluctuation of the exposure. 
 
The pharmacokinetics of semaglutide have been extensively characterised in healthy subjects and 
patients with type 2 diabetes. Following oral administration, maximum plasma concentration of 
semaglutide occurred 1 hour post dose. Steady-state exposure was reached after 4–5 weeks of once-
daily administration. In patients with type 2 diabetes, the average steady-state concentrations were 
approximately 6.7 nmol/L and 14.6 nmol/L with semaglutide 7 mg and 14 mg, respectively; with 90% 
of subjects treated with semaglutide 7 mg having an average concentration between 1.7 and 
22.7 nmol/L and 90% of subjects treated with semaglutide 14 mg having an average concentration 
between 3.7 and 41.3 nmol/L. Systemic exposure of semaglutide increased in a dose-proportional 
manner. 
 
Based on in vitro data, salcaprozate sodium facilitates absorption of semaglutide. The absorption of 
semaglutide predominantly occurs in the stomach. 
 
The estimated bioavailability of semaglutide is approximately 1% following oral administration. The 
between-subject variability in absorption was high (coefficient of variation was approximately 100%). 
The estimation of the within-subject variability in bioavailability was not reliable. 
 
Absorption of semaglutide is decreased if taken with food or large volumes of water. A longer post-
dose fasting period results in higher absorption. 
 
Distribution 
 
The estimated absolute volume of distribution is approximately 8 L in subjects with type 2 diabetes. 
Semaglutide is extensively bound to plasma proteins (>99%). 
 
Biotransformation 
 
Semaglutide is metabolised through proteolytic cleavage of the peptide backbone and sequential beta-
oxidation of the fatty acid sidechain. The enzyme neutral endopeptidase (NEP) is expected to be 
involved in the metabolism of semaglutide. 
 
Elimination 
 
The primary excretion routes of semaglutide-related material are via the urine and faeces. 
Approximately 3% of the absorbed dose is excreted as intact semaglutide via the urine. 



17 

 
With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation 
for about 5 weeks after the last dose. The clearance of semaglutide in patients with type 2 diabetes is 
approximately 0.04 L/h. 
 
Switching between oral and subcutaneous (s.c.) administration 
 
The effect of switching between oral and s.c. semaglutide cannot easily be predicted because of the 
high pharmacokinetic variability of oral semaglutide. Exposure after oral semaglutide 14 mg once 
daily is comparable to s.c. semaglutide 0.5 mg once weekly. An oral dose equivalent to 1.0 mg of s.c. 
semaglutide has not been established. 
 
Special populations 
 
Elderly 
Age had no effect on the pharmacokinetics of semaglutide based on data from clinical trials, which 
studied patients up to 92 years of age. 
 
Gender 
Gender had no clinically meaningful effects on the pharmacokinetics of semaglutide. 
 
Race and ethnicity 
Race (White, Black or African-American, Asian) and ethnicity (Hispanic or Latino, not Hispanic or 
Latino) had no effect on the pharmacokinetics of semaglutide. 
 
Body weight 
Body weight had an effect on the exposure of semaglutide. Higher body weight was associated with 
lower exposure. Semaglutide provided adequate systemic exposure over the body weight range of 
40-188 kg evaluated in the clinical trials. 
 
Renal impairment 
Renal impairment did not impact the pharmacokinetics of semaglutide in a clinically relevant manner. 
The pharmacokinetics of semaglutide were evaluated in patients with mild, moderate or severe renal 
impairment and patients with end-stage renal disease on dialysis compared with subjects with normal 
renal function in a study with 10 consecutive days of once-daily doses of semaglutide. This was also 
shown for subjects with type 2 diabetes and renal impairment based on data from phase 3a studies. 
 
Hepatic impairment 
Hepatic impairment did not impact the pharmacokinetics of semaglutide in a clinically relevant 
manner. The pharmacokinetics of semaglutide were evaluated in patients with mild, moderate or 
severe hepatic impairment compared with subjects with normal hepatic function in a study with 10 
consecutive days of once-daily doses of semaglutide. 
 
Upper GI tract disease 
Upper GI tract disease (chronic gastritis and/or gastroesophageal reflux disease) did not impact the 
pharmacokinetics of semaglutide in a clinically relevant manner. The pharmacokinetics were 
evaluated in patients with type 2 diabetes with or without upper GI tract disease dosed for 10 
consecutive days with once-daily doses of semaglutide. This was also shown for subjects with type 2 
diabetes and upper GI tract disease based on data from phase 3a studies. 
 
Paediatric population 
Semaglutide has not been studied in paediatric patients. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity or genotoxicity. 



18 

 
Non-lethal thyroid C-cell tumours observed in rodents are a class effect for GLP-1 receptor agonists. 
In 2-year carcinogenicity studies in rats and mice, semaglutide caused thyroid C-cell tumours at 
clinically relevant exposures. No other treatment-related tumours were observed. The rodent C-cell 
tumours are caused by a non-genotoxic, specific GLP-1 receptor mediated mechanism to which 
rodents are particularly sensitive. The relevance for humans is considered to be low, but cannot be 
completely excluded. 
 
In fertility studies in rats, semaglutide did not affect mating performance or male fertility. In female 
rats, an increase in oestrous cycle length and a small reduction in corpora lutea (ovulations) were 
observed at doses associated with maternal body weight loss. 
 
In embryo-foetal development studies in rats, semaglutide caused embryotoxicity below clinically 
relevant exposures. Semaglutide caused marked reductions in maternal body weight and reductions in 
embryonic survival and growth. In foetuses, major skeletal and visceral malformations were observed, 
including effects on long bones, ribs, vertebrae, tail, blood vessels and brain ventricles. Mechanistic 
evaluations indicated that the embryotoxicity involved a GLP-1 receptor mediated impairment of the 
nutrient supply to the embryo across the rat yolk sac. Due to species differences in yolk sac anatomy 
and function, and due to the lack of GLP-1 receptor expression in the yolk sac of non-human primates, 
this mechanism is considered unlikely to be of relevance to humans. However, a direct effect of 
semaglutide on the foetus cannot be excluded. 
 
In developmental toxicity studies in rabbits and cynomolgus monkeys, increased pregnancy loss and 
slightly increased incidence of foetal abnormalities were observed at clinically relevant exposures. The 
findings coincided with marked maternal body weight loss of up to 16%. Whether these effects are 
related to the decreased maternal food consumption as a direct GLP-1 effect is unknown. 
 
Postnatal growth and development were evaluated in cynomolgus monkeys. Infants were slightly 
smaller at delivery, but recovered during the lactation period. 
 
In juvenile rats, semaglutide caused delayed sexual maturation in both males and females. These 
delays had no impact upon fertility and reproductive capacity of either sex, or on the ability of the 
females to maintain pregnancy. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Salcaprozate sodium  
Povidone K90 
Cellulose, microcrystalline 
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 mg: 24 months 
7 mg: 30 months 
14 mg: 30 months. 
 
6.4 Special precautions for storage 
 



19 

Store in the original blister package in order to protect from light and moisture. This medicinal product 
does not require any special temperature storage conditions. 
 
6.5 Nature and contents of container 
 
Alu/Alu blisters.  
Pack sizes of 3 mg tablets: 10, 30, 60, 90 and 100 tablets. 
Pack sizes of 7 mg tablets: 30, 60, 90 and 100 tablets. 
Pack sizes of 14 mg tablets: 30, 60, 90 and 100 tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/20/1430/001 
EU/1/20/1430/002 
EU/1/20/1430/003 
EU/1/20/1430/004 
EU/1/20/1430/005 
EU/1/20/1430/006 
EU/1/20/1430/007 
EU/1/20/1430/008 
EU/1/20/1430/009 
EU/1/20/1430/010 
EU/1/20/1430/011 
EU/1/20/1430/012 
EU/1/20/1430/013 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 03 April 2020 
 
 
10. DATE OF REVISION OF THE TEXT  
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



21 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Novo Nordisk A/S 
Hallas Allé 
DK-4400 Kalundborg 
Denmark 
 
Hovione FarmaCiencia S.A. 
Quinta Sao Pedro, Sete Casas 
PT-2674-506 Loures 
Portugal 
 
Name and address of the manufacturer responsible for batch release 
 
Novo Nordisk A/S 
Novo Allé 
DK-2800 Bagsværd 
Denmark 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 3 mg tablets 
semaglutide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each tablet contains 3 mg of semaglutide 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. 
See package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 tablets 
30 tablets 
60 tablets 
90 tablets 
100 tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
How to take Rybelsus 
Take on an empty stomach at any time of the day 
Take the tablet whole with a sip of water (up to 120 ml). Do not split, crush or chew 
Wait at least 30 minutes before eating, drinking or taking any other oral medicines 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



25 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original blister package in order to protect from light and moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/20/1430/001   10 tablets 
EU/1/20/1430/002   30 tablets 
EU/1/20/1430/003   60 tablets 
EU/1/20/1430/004   90 tablets 
EU/1/20/1430/011   100 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rybelsus 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN  



26 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 3 mg tablets 
semaglutide 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 7 mg tablets 
semaglutide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each tablet contains 7 mg of semaglutide 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. 
See package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 tablets 
60 tablets 
90 tablets 
100 tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
How to take Rybelsus 
Take on an empty stomach at any time of the day 
Take the tablet whole with a sip of water (up to 120 ml). Do not split, crush or chew 
Wait at least 30 minutes before eating, drinking or taking any other oral medicines 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



28 

 
Store in the original blister package in order to protect from light and moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/20/1430/005   30 tablets 
EU/1/20/1430/006   60 tablets 
EU/1/20/1430/007   90 tablets 
EU/1/20/1430/012   100 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rybelsus 7 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



29 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 7 mg tablets 
semaglutide 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 14 mg tablets 
semaglutide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each tablet contains 14 mg of semaglutide 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. 
See package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 tablets 
60 tablets 
90 tablets 
100 tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
How to take Rybelsus 
Take on an empty stomach at any time of the day 
Take the tablet whole with a sip of water (up to 120 ml). Do not split, crush or chew 
Wait at least 30 minutes before eating, drinking or taking any other oral medicines 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



31 

 
Store in the original blister package in order to protect from light and moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/20/1430/008   30 tablets 
EU/1/20/1430/009   60 tablets 
EU/1/20/1430/010   90 tablets 
EU/1/20/1430/013   100 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rybelsus 14 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



32 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rybelsus 14 mg tablets 
semaglutide 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



34 

Package leaflet: Information for the patient 
 

Rybelsus 3 mg tablets 
Rybelsus 7 mg tablets 

Rybelsus 14 mg tablets 
semaglutide 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
– Keep this leaflet. You may need to read it again.  
– If you have any further questions, ask your doctor, pharmacist or nurse. 
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
– If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Rybelsus is and what it is used for  
2. What you need to know before you take Rybelsus  
3. How to take Rybelsus  
4. Possible side effects  
5. How to store Rybelsus  
6. Contents of the pack and other information 
 
 
1. What Rybelsus is and what it is used for 
 
Rybelsus contains the active substance semaglutide. It is a medicine that is used to lower blood sugar 
levels. 
 
Rybelsus is used to treat adults (aged 18 years and older) with type 2 diabetes when diet and exercise 
is not enough: 
• on its own – when you cannot use metformin (another diabetes medicine) or 
• with other medicines for diabetes – when the other medicines are not enough to control your 

blood sugar levels. These may be medicines you take by mouth or inject such as insulin. 
 
It is important that you continue with your diet and exercise plan as agreed with your doctor, 
pharmacist or nurse. 
 
What is type 2 diabetes? 
Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that 
your body makes does not lower your blood sugar the way it should. In some cases, your body can 
produce too much blood sugar. If your blood sugar increases and remains high over a long period of 
time, this can lead to harmful effects such as heart problems, kidney disease, eye disorders and poor 
circulation in your limbs. That is why it is important to keep your blood sugar levels within a normal 
range. 
 
 
2. What you need to know before you take Rybelsus 
 
Do not take Rybelsus 



35 

• if you are allergic to semaglutide or any of the other ingredients of this medicine (listed in 
section 6). 

 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before taking Rybelsus. 
 
Traceability 
In order to improve the traceability of biological medicinal products, record the name and the lot 
number (included on the outer cartons and blister) of the medicine you are taking and provide this 
information when reporting any side effects. 
 
General: 
This medicine is not the same as insulin and you should not use it if: 
• you have type 1 diabetes (your body does not produce any insulin) 
• you develop diabetic ketoacidosis. This is a complication of diabetes with high blood sugar, 

breathing difficulty, confusion, excessive thirst, a sweet smell to the breath or a sweet or 
metallic taste in the mouth. 

 
Stomach and gut problems  
During treatment with this medicine, you may feel sick (nausea) or be sick (vomiting), or have 
diarrhoea. These side effects can cause dehydration (loss of fluids). It is important that you drink 
enough fluids to prevent dehydration. This is especially important if you have kidney problems. Talk 
to your doctor if you have any questions or concerns. 
 
Severe and on-going stomach pain which could be due to an inflamed pancreas 
If you have severe and on-going pain in the stomach area – see a doctor straight away as this could be 
a sign of inflamed pancreas (acute pancreatitis). 
 
Low blood sugar (hypoglycaemia) 
Taking a sulfonylurea medicine or insulin with Rybelsus might increase the risk of getting low blood 
sugar (hypoglycaemia). See section 4 for the warning signs of low blood sugar levels.  
 
Your doctor may ask you to test your blood sugar levels. This will help to decide if the dose of the 
sulfonylurea or insulin needs to be changed to reduce the risk of low blood sugar. 
 
Diabetic eye disease (retinopathy) 
Fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disease. 
If you have diabetic eye disease and get eye problems while taking this medicine, talk to your doctor. 
 
Treatment response 
If the treatment response with semaglutide is lower than expected, this may be due to low absorption 
caused by variability in absorption and low absolute bioavailability. You should follow the 
instructions given in section 3 for optimal effect of semaglutide. 
 
Children and adolescents 
This medicine is not recommended in children and adolescents aged under 18 years as the safety and 
efficacy in this age group have not been established. 
 
Other medicines and Rybelsus 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
In particular, tell your doctor, pharmacist or nurse if you are using medicines containing any of the 
following: 
• levothyroxine which is used for thyroid disease. This is because your doctor may need to check 

your thyroid levels if you are taking Rybelsus together with levothyroxine. 



36 

• warfarin or similar medicines taken by mouth to reduce blood clotting (oral anti-coagulants). 
You may need frequent blood tests to check how quickly your blood clots. 

• If you are using insulin, your doctor will tell you how to reduce the dose of insulin and will 
recommend you to monitor your blood sugar more frequently, in order to avoid hyperglycaemia 
(high blood sugar) and diabetic ketoacidosis (a complication of diabetes that occurs when the 
body is unable to breakdown glucose because there is not enough insulin). 

 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
This medicine should not be used during pregnancy, as it is not known if it affects your unborn baby. 
Therefore, use of contraception is recommended while taking this medicine. If you wish to become 
pregnant, discuss how to change your treatment with your doctor as you should stop using this 
medicine at least 2 months in advance. If you become pregnant while using this medicine, talk to your 
doctor straight away, as your treatment will need to be changed. 
 
Do not use this medicine if you are breast-feeding, as it is unknown if it passes into breast milk. 
 
Driving and using machines 
If you use this medicine in combination with a sulfonylurea or insulin, low blood sugar 
(hypoglycaemia) may occur which may reduce your ability to concentrate. Do not drive or use 
machines if you get any signs of low blood sugar. See section 2, ‘Warning and precautions’ for 
information on increased risk of low blood sugar and section 4 for the warning signs of low blood 
sugar. Talk to your doctor for further information. 
 
Rybelsus contains sodium 
This medicine contains 23 mg sodium (main component of cooking/table salt) in each tablet. This is 
equivalent to 1% of the recommended maximum daily dietary intake of sodium for an adult. 
 
 
3. How to take Rybelsus 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
How much to take 
• The starting dose is one 3 mg tablet once a day for one month. 
• After one month, your doctor will increase your dose to 7 mg once a day. 
• Your doctor may increase your dose to 14 mg once a day if your blood sugar is not controlled 

well enough with a dose of 7 mg once a day. 
Your doctor will prescribe the strength that is right for you. Do not change your dose unless your 
doctor has told you so. It is not recommended to take two 7 mg tablets to get the effect of one 14 mg 
tablet, as this has not been studied. 
 
Taking this medicine 
• Take your Rybelsus tablet on an empty stomach at any time of the day. 
• Swallow your Rybelsus tablet whole with a sip of water (up to 120 ml). Do not split, crush or 

chew the tablet, as it is not known if it affects absorption of semaglutide. 
• After taking your Rybelsus tablet wait at least 30 minutes before having your first meal or drink 

of the day or taking other oral medicines. Waiting less than 30 minutes lowers the absorption of 
semaglutide. 

 
If you take more Rybelsus than you should 
If you take more Rybelsus than you should, talk to your doctor straight away. You may get side effects 
such as feeling sick (nausea).  
 



37 

If you forget to take Rybelsus 
If you forget to take a dose, skip the missed dose and just take your normal dose the next day. 
 
If you stop taking Rybelsus 
Do not stop using this medicine without talking to your doctor. If you stop using it, your blood sugar 
levels may increase.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
 
Common (may affect up to 1 in 10 people) 
• complications of diabetic eye disease (retinopathy). You should tell your doctor if you get eye 

problems, such as changes in vision, during treatment with this medicine.  
 
Rare (may affect up to 1 in 1,000 people) 
• serious allergic reactions (anaphylactic reactions). You must get immediate medical help and 

inform your doctor straight away if you get symptoms such as breathing problems, swelling of 
face and throat, wheezing, fast heartbeat, pale and cold skin, feeling dizzy or weak. 

• inflamed pancreas (acute pancreatitis) which could cause severe pain in the stomach and back 
which does not go away. You should see a doctor immediately if you experience such 
symptoms. 

 
Other side effects 
 
Very common (may affect more than 1 in 10 people) 
• feeling sick (nausea) – this usually goes away over time 
• diarrhoea – this usually goes away over time 
• low blood sugar (hypoglycaemia) when this medicine is used with medicines that contain a 

sulfonylurea or insulin. Your doctor may reduce your dose of these medicines before you start 
using this medicine. 

 
The warning signs of low blood sugar may come on suddenly. They can include: cold sweat, cool pale 
skin, headache, fast heartbeat, feeling sick (nausea) or very hungry, changes in vision, feeling sleepy 
or weak, feeling nervous, anxious or confused, difficulty concentrating or shaking. 
Your doctor will tell you how to treat low blood sugar and what to do if you notice these warning 
signs. 
 
Common (may affect up to 1 in 10 people) 
• low blood sugar (hypoglycaemia) when this medicine is used with oral diabetes medicine other 

than sulfonylurea or insulin 
• being sick (vomiting) 
• upset stomach or indigestion 
• inflamed stomach (‘gastritis’) – the signs include stomach ache, feeling sick (nausea) or being 

sick (vomiting) 
• reflux or heartburn – also called ‘gastro-esophageal reflux disease’ 
• stomach pain 
• bloating of the stomach 
• constipation 
• tiredness 
• less appetite 
• gas (flatulence) 



38 

• increase of pancreatic enzymes (such as lipase and amylase) shown in blood tests. 
 
Uncommon (may affect up to 1 in 100 people) 
• weight loss 
• gallstones 
• burping 
• fast pulse. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Rybelsus 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and carton after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from light and moisture. This medicine does not 
require any special temperature storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Rybelsus contains  
• The active substance is semaglutide. Each tablet contains 3, 7 or 14 mg semaglutide. 
• The other ingredients are salcaprozate sodium, povidone K90, cellulose microcrystalline, 

magnesium stearate. 
 
What Rybelsus looks like and contents of the pack 
Rybelsus 3 mg tablets are white to light yellow and oval shaped (7.5 mm x 13.5 mm). They have ‘3’ 
on one side and ‘novo’ on the other side. 
Rybelsus 7 mg tablets are white to light yellow and oval shaped (7.5 mm x 13.5 mm). They have ‘7’ 
on one side and ‘novo’ on the other side. 
Rybelsus 14 mg tablets are white to light yellow and oval shaped (7.5 mm x 13.5 mm). They have ‘14’ 
on one side and ‘novo’ on the other side. 
 
The 3 mg tablets are available in alu/alu blister cards in pack sizes of 10, 30, 60, 90 and 100 tablets. 
The 7 mg and 14 mg tablets are available in alu/alu blister cards in pack sizes of 30, 60, 90 and 100 
tablets. 
 
Not all pack sizes may be marketed in your country. 
 
Marketing Authorisation Holder and Manufacturer 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
This leaflet was last revised in  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


39 

 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET