WEGOVY 0.5 MG SOLUTION FOR INJECTION IN PRE-FILLED PEN - summary of medicine characteristics

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

Wegovy 0.5 mg, solution for injection in pre-filled pen

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Wegovy 0.5 mg solution for injection

Each pre-filled pen contains 0.5 mg semaglutide* in 0.5 mL

*human glucagon-like peptide-1 (GLP-1) analogue produced in Saccharomyces cerevisiae cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection

Clear and colourless isotonic solution; pH=7.4.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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.

Refer to section 5.1 for further information on weight-related comorbordities.

4.2 Posology and method of administration

Posology

The maintenance dose of 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 1). In case of significant gastrointestinal symptoms, consider delaying dose escalation or lowering to the previous dose until symptoms have improved.

If patients have been unable to lose at least 5% of their initial body weight after 6 months on treatment, a decision is required on whether to continue treatment, taking into account the benefit/risk profile in the individual patient (see section 5.1).

Table 1 Dose escalation schedule

Weekly doses higher than 2.4 mg are not recommended.

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

Patients with type 2 diabetes

Semaglutide should not be used in combination with other GLP-1 receptor agonist products.

When initiating semaglutide, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia.

Elderly patients (>65 years old)

No dose adjustment is required based on age. Therapeutic experience in patients >75 years of age is limited.

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 endstage renal disease (see section 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. Caution should be exercised when treating these patients with semaglutide (see section 5.2).

Paediatric population

The safety and efficacy of semaglutide in children and adolescents below 18 years have not yet been established. No data are available.

Method of administration

Wegovy is administered once weekly at any time of the day, with or without meals.

It is to be injected subcutaneously in the abdomen, in the thigh or in the upper arm. The injection site can be changed. It should not be administered intravenously or intramuscularly.

The day of weekly administration can be changed if necessary as long as the time between two doses is at least 3 days (>72 hours). After selecting a new dosing day, once-weekly dosing should be continued.

When administering Wegovy, the pen should be pressed firmly against the skin until the yellow bar has stopped moving. The injection takes about 5–10 seconds.

Patients should be advised to read the instruction for use included in the package leaflet carefully before administering the medicinal product.

For further information on administration see section 6.6.

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

Gastrointestinal effects

Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions that can cause dehydration, which in rare cases can lead to a deterioration of renal function. Patients □ should □ be □ advised of the potential risk of dehydration Din 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.

In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.

For patients with diabetes

Semaglutide must not be used as a substitute for insulin in patients with diabetes.

Hypoglycaemia in patients with 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 agonist. The addition of semaglutide 2.4 mg in patients treated with insulin has not been evaluated.

Diabetic retinopathy in patients with type 2 diabetes

In patients with diabetic retinopathy treated with insulin and semaglutide, an increased risk of developing diabetic retinopathy complications has been observed. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. Patients with diabetic retinopathy using semaglutide should be monitored closely and treated according to clinical guidelines. There is no experience with semaglutide 2.4 mg in patients with type 2 diabetes with uncontrolled or potentially unstable diabetic retinopathy.

Populations not studied

There is no experience in patients with congestive heart failure New York Heart Association (NYHA) class IV. There is limited experience in patients aged 75 years or more.

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

As with other GLP-1 receptor agonists, semaglutide may delay 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. In clinical pharmacology trials assessing the effect of semaglutide 1.0 mg on the absorption of co-administered oral medications at steady state, no clinically relevant drug-drug interactions with semaglutide was observed based on the evaluated medications. Therefore, no dose adjustment is required when co-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 coadministered 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.

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

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 were not affected in a clinically relevant manner.

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 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.

4.7 Effects on ability to drive and use machines

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).

4.8 Undesirable effects

Summary of safety profile

In 4 phase 3a trials, 2,650 patients were exposed to semaglutide 2.4 mg. The duration of the trials was 68 weeks. Similar to other GLP-1 receptor agonists, the most frequently reported adverse reactions were gastrointestinal disorders including nausea, diarrhoea, constipation and vomiting.

Tabulated list of adverse reactions

Table 2 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 semaglutide 2.4 mg are listed by body system 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).

Table 2 Adverse reactions from controlled phase 3 trials

b) Mainly seen in the dose-escalation period c) Grouped preferred terms

Description of selected adverse reactions

Gastrointestinal adverse reactions

The events were most frequently reported during dose escalation. Over 68 weeks, nausea occurred in 43.9% of patients when treated with semaglutide 2.4 mg (16.1% for placebo), diarrhoea in 29.7% (15.9% for placebo) and vomiting in 24.5% (6.3% for placebo). Most events were mild to moderate in severity and of short duration. Constipation occurred in 24.2% of patients treated with semaglutide 2.4 mg (11.1% for placebo) and was mild to moderate in severity and of longer duration.

The gastrointestinal events led to permanent treatment discontinuation in 4.3% of patients.

Acute pancreatitis

The frequency of adjudication-confirmed acute pancreatitis reported in phase 3a clinical trials was 0.2% for semaglutide 2.4 mg and <0.1% for placebo, respectively.

Acute gallstone disease/Chole­lithiasis

Cholelithiasis was reported in 1.6% and led to cholecystitis in 0.6% of patients treated with semaglutide 2.4 mg.

Hair loss

Hair loss was reported in 2.5% of patients treated with semaglutide 2.4 mg and in 1.0% of patients treated with placebo. The events were mainly of mild severity and most patients recovered while on continued treatment. Hair loss was reported more frequently in patients with a greater weight loss (>20%).

Increased heart rate

In the phase 3a trials, a mean increase of 3 beats per minute (bpm) from a baseline mean of 72 bpm was observed in patients treated with semaglutide 2.4 mg. The proportions of patients with a maximum increase from baseline >20 bpm/min at any timepoint during the on-treatment period were 26.0% in the semaglutide 2.4 mg group vs 15.6% in the placebo group.

Immunogenicity

Consistent with the potentially immunogenic properties of medicinal products containing proteins or peptides, patients may develop antibodies following treatment with semaglutide. The proportion of patients testing positive for anti-semaglutide antibodies at any time post-baseline was low (2.9%) and no patients had anti-semaglutide neutralising antibodies or anti-semaglutide antibodies with endogenous GLP-1 neutralising effect at end-of-trial.

Hypoglycaemia in patients with type 2 diabetes

In STEP 2, clinically significant hypoglycaemia was observed in 6.2% (0.1 events/patient year) of patients treated with semaglutide 2.4 mg compared with 2.5% (0.03 events/pa­tient year) of patients treated with placebo. One episode (0.2% of subjects, 0.002 events/pa­tient year) was reported as severe. The risk of hypoglycaemia was increased when semaglutide 2.4 mg was used with a sulfonylurea.

Diabetic retinopathy in patients with type 2 diabetes

New onset or worsening of diabetic retinopathy (4.0% vs 2.7% of patients treated with semaglutide 2.4 mg vs placebo, respectively) was observed in STEP 2.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

5.2 Pharmacokinetic properties

Compared to native GLP-1, semaglutide has a prolonged half-life of around 1 week making it suitable for once weekly subcutaneous administration. The principal mechanism of protraction is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilised against degradation by the DPP-4 enzyme.

Absorption

The average semaglutide steady state concentration following s.c. administration of semaglutide 2.4 mg was approximately 75 nmol/L in patients with overweight (BMI >27 kg/m2 to <30 kg/m2) or obesity (BMI > 30 kg/m2). The steady state exposure of semaglutide increased proportionally with doses up to 2.4 mg once weekly. Similar exposure was achieved with s.c. administration of semaglutide in the abdomen, thigh, or upper arm. The absolute bioavailability of semaglutide was 89%.

Distribution

The mean volume of distribution of semaglutide following s.c. administration in patients with overweight or obesity was approximately 12.4 L. Semaglutide is extensively bound to plasma albumin (>99%).

Metabolism/Bi­otransformati­on

Prior to excretion, semaglutide is extensively metabolised through proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid side chain. 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 was excreted in the urine as intact semaglutide.

The clearance of semaglutide in patients with overweight (BMI >27 kg/m2 to <30 kg/m2) or obesity (BMI > 30 kg/m2) was approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for approximately 7 weeks after the last dose of 2.4 mg.

Special populations

Elderly

Age had no effect on the pharmacokinetics of semaglutide based on data from phase 3a trials including patients 18–86 years of age.

Gender, race and ethnicity

Gender, race (White, Black or African-American, Asian) and ethnicity (Hispanic or Latino, non-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. The 2.4 mg weekly dose of semaglutide provided adequate systemic exposures over the body weight range of 54.4–245.6 kg evaluated for exposure response in the clinical trials.

Renal Impairment

Renal impairment did not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was shown with a single dose of 0.5 mg semaglutide for patients with different degrees of renal impairment (mild, moderate, severe or patients in dialysis) compared with patients with normal renal function. This was also shown for patients with overweight (BMI >27 kg/m2 to <30 kg/m2) or obesity (BMI > 30 kg/m2) and mild to moderate renal impairment based on data from phase 3a trials.

Hepatic impairment

Hepatic impairment did not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) and compared with patients with normal hepatic function in a study with a single-dose of 0.5 mg semaglutide.

Paediatrics

Safety and efficacy of semaglutide 2.4 mg in children and adolescents below 18 years of age has not been studied.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium phosphate, dihydrate

Sodium chloride

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injection

6.2 Incompatibilities

In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

24 months.

6.4 Special precautions for storage

Store in a refrigerator (2°C to 8°C). Keep away from the cooling element.

Do not freeze and do not use Wegovy if it has been frozen.

Store the pen in the original carton in order to protect from light.

Wegovy may be stored at up to 25°C for a single period of up to 21 days. The product must not be returned to the refrigerator.

6.5 Nature and contents of container

1 mL glass syringe (type I glass) with attached stainless steel needle, rigid needle shield (type II/polyisoprene) and a rubber plunger (type I/chlorobutyl). The syringe is assembled into a disposable pre-filled pen made of stainless steel, polyoxymethylene and acrylonitrile butadiene styrene. For safety, the needle is only exposed when the needle cover is retracted during injection and, following the injection, the needle cover returns to the initial position and locks.

Pack sizes:

Wegovy 0.5 mg solution for injection: Each pre-filled pen contains 0.5 mL solution, delivering 1 dose of 0.5 mg.

4 pre-filled pens

6.6 Special precautions for disposal

The pen is for single-use only.

Wegovy should not be used if it does not appear clear and colourless.

The pen should not be used if it has been frozen.

Any unused medicinal product, used pen or waste material should be disposed of in accordance with local requirements.