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Saxenda 6 mg/ml solution for injection in pre-filled pen 

1 ml of solution contains 6 mg of liraglutide^*. One pre-filled pen contains 18 mg liraglutide in 3 ml.

*human glucagon-like peptide-1 (GLP-1) analogue produced by recombinant DNA technology in Saccharomyces cerevisiae.
full list of excipients:
Disodium phosphate dihydrate
Propylene glycol
Phenol
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections

Solution for injection. 

Clear and colourless or almost colourless, isotonic solution; pH=8.15. 

Adults

Saxenda is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adult patients 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 such as dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia or obstructive sleep apnoea.

Treatment with Saxenda should be discontinued after 12 weeks on the 3.0 mg/day dose if patients have not lost at least 5% of their initial body weight. 

Adolescents (≥12 years)

Saxenda can be used as an adjunct to a healthy nutrition and increased physical activity for weight management in adolescent patients from the age of 12 years and above with: 

• obesity (BMI corresponding to ≥30 kg/m² for adults by international cut-off points)*  and body weight above 60 kg.  

Treatment with Saxenda should be discontinued and re-evaluated if patients have not lost at least 4% of their BMI or BMI z score after 12 weeks on the 3.0 mg/day or maximum tolerated dose.

*IOTF BMI cut-off points for obesity by sex between 12–18 years (see table 1): 

Table 1 IOTF BMI cut-off points for obesity by sex between 12–18 years

Posology Adults  

The starting dose is 0.6 mg once daily. The dose should be increased to 3.0 mg once daily in increments of 0.6 mg with at least one-week intervals to improve gastro-intestinal tolerability (see table 2). If escalation to the next dose step is not tolerated for two consecutive weeks, consider discontinuing treatment. Daily doses higher than 3.0 mg are not recommended. 

Table 2 Dose escalation schedule

Adolescents (≥12 years)

For adolescents from the age of 12 to below 18 years old a similar dose escalation schedule as for adults should be applied (see table 2). The dose should be increased until 3.0 mg (maintenance dose) or maximum tolerated dose has been reached. Daily doses higher than 3.0 mg are not recommended.  

Missed doses

If a dose is missed within 12 hours from when it is usually taken, the patient should take the dose as soon as possible. If there is less than 12 hours to the next dose, the patient should not take the missed dose and resume the once-daily regimen with the next scheduled dose. An extra dose or increase in dose should not be taken to make up for the missed dose.  

Patients with type 2 diabetes mellitus 

Saxenda should not be used in combination with another GLP-1 receptor agonist.  

When initiating Saxenda, it should be considered to reduce the dose of concomitantly administered insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia. Blood glucose self-monitoring is necessary to adjust the dose of insulin or insulin-secretagogues (see section 4.4 in Prescribing Information)

Special populations

Elderly (≥65 years old)

No dose adjustment is required based on age. Therapeutic experience in patients ≥75 years of age is limited and use in these patients is not recommended (see sections 4.4 and 5.2 in Prescribing Information). 

Renal impairment 

No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance ≥30 ml/min). Saxenda is not recommended for use in patients with severe renal impairment (creatinine clearance <30 ml/min) including patients with end-stage renal disease (see sections 4.4, 4.8 and 5.2 in Prescribing Information).  

Hepatic impairment  

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Saxenda is not recommended for use in patients with severe hepatic impairment and should be used cautiously in patients with mild or moderate hepatic impairment (see sections 4.4 and 5.2 in Prescribing Information). 

Paediatric population 


No dose adjustment is required for adolescents from the age of 12 years and above. 

The safety and efficacy of Saxenda in children below 12 years of age has not been established (see section 5.1 in Prescribing Information).

Method of administration

Saxenda is for subcutaneous use only. It must not be administered intravenously or intramuscularly.


Saxenda is administered once daily at any time, independent of meals. It should be injected in the abdomen, thigh or upper arm. The injection site and timing can be changed without dose adjustment. However, it is preferable that Saxenda is injected around the same time of the day, when the most convenient time of the day has been chosen. 


For further instructions on administration, see section 6.6 in Prescribing Information.

Hypersensitivity to liraglutide or to any of the excipients listed below:
Disodium phosphate dihydrate 
Propylene glycol 
Phenol 
Hydrochloric acid (for pH adjustment) 
Sodium hydroxide (for pH adjustment) 
Water for injections

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. 

Patients with heart failure


There is no clinical experience in patients with congestive heart failure New York Heart Association (NYHA) class IV, and liraglutide is therefore not recommended for use in these patients. 

Special populations

The safety and efficacy of liraglutide for weight management have not been established in patients: 
-  aged 75 years or more,
-  treated with other products for weight management,
-  with obesity secondary to endocrinological or eating disorders or to treatment with medicinal products that may cause weight gain,
-  with severe renal impairment,
-  with severe hepatic impairment. 

Use in these patients is not recommended (see section 4.2 in Prescribing Information).
As liraglutide for weight management was not investigated in subjects with mild or moderate hepatic impairment, it should be used with caution in these patients (see sections 4.2 and 5.2 in Prescribing Information).

There is limited experience in patients with inflammatory bowel disease and diabetic gastroparesis. Use of liraglutide is not recommended in these patients since it is associated with transient gastrointestinal adverse reactions, including nausea, vomiting and diarrhoea. 

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, liraglutide should be discontinued; if acute pancreatitis is confirmed, liraglutide should not be restarted.  

Cholelithiasis and cholecystitis

In clinical trials for weight management, a higher rate of cholelithiasis and cholecystitis was observed in patients treated with liraglutide than in patients on placebo. The fact that substantial weight loss can increase the risk of cholelithiasis and thereby cholecystitis only partially explained the higher rate with liraglutide. Cholelithiasis and cholecystitis may lead to hospitalisation and cholecystectomy. Patients should be informed of the characteristic symptoms of cholelithiasis and cholecystitis. 


Thyroid disease

In clinical trials in type 2 diabetes, thyroid adverse events, such as goitre, have been reported in particular in patients with pre-existing thyroid disease. Liraglutide should therefore be used with caution in patients with thyroid disease. 

Heart rate

An increase in heart rate was observed with liraglutide in clinical trials (see section 5.1 in Prescribing Information). Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should be informed of the symptoms of increased heart rate (palpitations or feelings of a racing heartbeat while at rest). For patients who experience a clinically relevant sustained increase in resting heart rate, treatment with liraglutide should be discontinued. 

Dehydration

Signs and symptoms of dehydration, including renal impairment and acute renal failure, have been reported in patients treated with GLP-1 receptor agonists. Patients treated with liraglutide should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion. 

Hypoglycaemia in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus receiving liraglutide in combination with insulin and/or sulfonylurea may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of insulin and/or sulfonylurea. 

Paediatric population

Episodes of clinically significant hypoglycaemia have been reported in adolescents (≥12 years) treated with liraglutide. Patients should be informed about the characteristic symptoms of hypoglycaemia and the appropriate actions.  

Hyperglycaemia in insulin treated patients with diabetes mellitus  

In patients with diabetes mellitus Saxenda must not be used as a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin (see section 4.2 in Prescribing Information).

Excipients

Saxenda contains less than 1 mmol sodium (23 mg) per dose, therefore the medicinal product is essentially ‘sodium-free’. 

In vitro, liraglutide has shown very low potential to be involved in pharmacokinetic interactions with other active substances related to cytochrome P450 (CYP) and plasma protein binding.

The small delay of gastric emptying with liraglutide may influence absorption of concomitantly administered oral medicinal products. Interaction studies did not show any clinically relevant delay of absorption and therefore no dose adjustment is required. 

Interaction studies have been performed with 1.8 mg liraglutide. The effect on rate of gastric emptying was equivalent between liraglutide 1.8 mg and 3.0 mg, (paracetamol AUC0-300 min). Few patients treated with liraglutide reported at least one episode of severe diarrhoea. Diarrhoea may affect the absorption of concomitant oral medicinal products.  

Warfarin and other coumarin derivatives

No interaction study has been performed. A clinically relevant interaction with active substances with poor solubility or narrow therapeutic index such as warfarin cannot be excluded. Upon initiation of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of International Normalised Ratio (INR) is recommended. 

Paracetamol (Acetaminophen)

Liraglutide did not change the overall exposure of paracetamol following a single dose of 1,000 mg. Paracetamol Cmax was decreased by 31% and median tmax was delayed up to 15 min. No dose adjustment for concomitant use of paracetamol is required. 

Atorvastatin

Liraglutide did not change the overall exposure of atorvastatin following single dose administration of atorvastatin 40 mg. Therefore, no dose adjustment of atorvastatin is required when given with liraglutide. Atorvastatin Cmax was decreased by 38% and median tmax was delayed from 1 h to 3 h with liraglutide. 

Griseofulvin

Liraglutide did not change the overall exposure of griseofulvin following administration of a single dose of griseofulvin 500 mg. Griseofulvin Cmax increased by 37% while median tmax did not change. Dose adjustments of griseofulvin and other compounds with low solubility and high permeability are not required. 

Digoxin  

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC by 16%; Cmax decreased by 31%. Digoxin median tmax was delayed from 1 h to 1.5 h. No dose adjustment of digoxin is required based on these results.  

Lisinopril

A single dose administration of lisinopril 20 mg with liraglutide resulted in a reduction of lisinopril AUC by 15%; Cmax decreased by 27%. Lisinopril median tmax was delayed from 6 h to 8 h with liraglutide. No dose adjustment of lisinopril is required based on these results. 

Oral contraceptives

Liraglutide lowered ethinylestradiol and levonorgestrel Cmax by 12% and 13%, respectively, following administration of a single dose of an oral contraceptive product. tmax was delayed by 1.5 h with liraglutide for both compounds. There was no clinically relevant effect on the overall exposure of either ethinylestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to be unaffected when co-administered with liraglutide. 

Paediatric population  
Interaction studies have only been performed in adults. 

 Pregnancy 

There are limited data from the use of liraglutide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3 in Prescribing Information). The potential risk for humans is unknown. 
Liraglutide should not be used during pregnancy. If a patient wishes to become pregnant or pregnancy occurs, treatment with liraglutide should be discontinued. 

Breast-feeding 

It is not known whether liraglutide is excreted in human milk. Animal studies have shown that the transfer of liraglutide and metabolites of close structural relationship into milk is low. Non-clinical studies have shown a treatment-related reduction of neonatal growth in suckling rat pups (see section 5.3 in Prescribing Information). Because of lack of experience, Saxenda should not be used during breast-feeding. 

Fertility 

Apart from a slight decrease in the number of live implants, animal studies did not indicate harmful effects with respect to fertility (see section 5.3 in Prescribing Information).

Saxenda has no or negligible influence on the ability to drive and use machines. However, dizziness can be experienced mainly during the first 3 months of treatment with Saxenda. Driving or use of machines should be exercised with caution if dizziness occurs. 

From clinical trials and post-marketing use of liraglutide overdoses have been reported up to 72 mg (24 times the recommended dose for weight management). Events reported included severe nausea, severe vomiting and severe hypoglycaemia. 

In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. The patient should be observed for clinical signs of dehydration and blood glucose should be monitored.