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

Addition of a paragraph on Aspiration in association with general anaesthesia or deep sedation to Section 4.4.

-Addition of the following sentence to Section 2, Warnings and precautions:

If you know that you are due to have surgery where you will be under anesthesia (sleeping), please tell your doctor that you are taking Saxenda.

-Removal of United Kingdom (Northern Ireland) adverse event reporting details from Section 4

Section 4: Addition of Bowel obstruction as side effect with a frequency of Not Known (cannot be estimated from the available data)

Minor formatting changes throughout.

Section 4.8 - Addition of Intestinal Obstruction as an adverse reaction with a frequency of 'not known' (cannot be estimated from the available data).

Minor formatting changes throughout.

Rash added to 4.8  Undesirable effects 

Rash added to side effects section.

Instructions for use section updated to make wording clearer and provide more detailed instructions.

Section 5.1, new text added:

A 16-week double-blind, 36 week open-label study was conducted to evaluate the efficacy and safety of Saxenda in paediatric patients with Prader-Willi Syndrome and obesity. The study included 32 patients between 12 to <18 years of age (part A) and 24 patients between 6 to <12 years of age (part B). Patients were randomized 2:1 to receive Saxenda or placebo. Patients with a body weight less than 45 kg started dose escalation at a lower dose; 0.3 mg instead of 0.6 mg and were escalated to a maximum dose of 2.4 mg.

The estimated treatment difference in mean BMI SDS at 16 weeks (part A: -0.20 vs -0.13, part B: -0.50 vs -0.44) and 52 weeks (part A: -0.31 vs -0.17, part B: -0.73 vs -0.67) were similar with Saxenda and placebo. 

No additional safety concerns were seen in the trial.

Section 10: 

revision date updated to 12/2021

Section 4

'Headache' added as a very common side effect

Section 6: 

Revision date updated to 11/2021

Section 4.8 Undesirable effects 

'Headache' added to Table 3 with a frequency of very common

File name corrected

Section 4 updated to include 'Northern Ireland'

Section 1

'What Saxenda is used for' updated to include:

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

•        obesity (diagnosed by your doctor)

•        body weight above 60 kg

You should only continue using Saxenda if you have lost at least 4% of your BMI after 12 weeks on the 3.0 mg/day dose or maximum tolerated dose (see section 3). Consult your doctor before you continue.

Section 2 - children and adolescents

Text update:

The safety and efficacy of Saxenda in children below 12 years of age has not been studied.

Saxenda® should not be used in children and adolescents under 18 years of age. This is because the effects and safety of this medicine have not been studied in this age group.

Section 3 - How much to inject

Text additions:

Adults

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 above table for adults). 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.

Section 6 - Date of revision

Revision date updated to: 04/2021

Section 4.1 - indication for adolescents from the age of 12 years added as follows:

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) (refer to SmPC for Table 1)

Section 4.2:

New text added:

Adults

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.

Text update:

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).

The safety and efficacy of Saxenda in children and adolescents below 18 years of age have not yet been established.  Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on posology can be made.

Section 4.4:

New text added:

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.

Section 4.5:

New text added:

Paediatric population

Interaction studies have only been performed in adults.

Section 4.8

Table 3 updated to clarify:

'Adverse reactions reported in adults'

Text update:

In a clinical trial conducted in adolescents of 12 years to less than 18 years with obesity, 125 patients were exposed to Saxenda for 56 weeks.

Overall, the frequency, type and severity of adverse reactions in the adolescents with obesity were comparable to that observed in the adult population. Vomiting occurred with a 2-fold higher frequency in adolescents compared to adults.

The percentage of patients reporting at least one episode of clinically significant hypoglycaemia was higher with liraglutide (1.6%) compared to placebo (0.8%). No severe hypoglycaemic episodes occurred in the trial.

Saxenda is not recommended for use in paediatric patients.  Gastrointestinal disorders were the most frequently reported adverse events in two dose escalation studies completed so far.

Section 5.1

'Paediatric Population' updated to include:

In a double-blind trial comparing the efficacy and safety of Saxenda versus placebo on weight loss in adolescent patients aged 12 years and above with obesity, Saxenda was superior to placebo in weight reduction (evaluated as BMI Standard Deviation Score) after 56 weeks of treatment (table 9).

A greater proportion of the patients achieved ≥5% and ≥10% reductions in BMI with liraglutide than with placebo, as well as greater reductions in mean BMI and body weight (table 9). After 26 weeks of off-trial product follow-up period, weight regain was observed with liraglutide vs placebo (table 9).

Refer to SmPC for Table 9.

Section 5.2

'Paediatric Population' updated:

Pharmacokinetic properties for liraglutide 3.0 mg were assessed in clinical studies for adolescent patients with obesity aged 12 to less than 18 years (134 patients, body weight 62-178 kg). The liraglutide exposure in adolescents (age 12 to less than 18 years) was similar to that in adults with obesity. 

Pharmacokinetic properties were also assessed in a clinical pharmacology study in the paediatric population with obesity aged 7-11 years (13 patients, body weight 54-87 kg) respectively.

Exposure associated with 3.0 mg liraglutide was found to be comparable between the children aged 7 to 11, adolescents and adults with obesity, after correction for body weight.

Section 5.3

Text added:

In juvenile rats, liraglutide caused delayed sexual maturation in both males and females at clinical relevant exposures. These delays had no impact upon fertility and reproductive capacity of either sex, or on the ability of the females to maintain pregnancy.

Section 10:

Date of Revision updated to: 04/2021

Section 3

If you use more Saxenda® than you should

If you use more Saxenda® than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you. You may need medical treatment. The following effects may happen:

•        feeling sick (nausea)

•        being sick (vomiting)

•        low blood sugar (hypoglycaemia). Please refer to ‘Common side effects’ for warning signs of low blood sugar.

Section 4.9

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, and severe vomiting and severe hypoglycaemia.  which are also the expected symptoms of an overdose with liraglutide. None of the reports included severe hypoglycaemia. All patients recovered without complications.

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.

Correction of missing image

Black triangle removed

Section 1

- Minor text update "Saxenda® is a weight loss medicine that contains the active substance liraglutide. It is similar to a natural occurring hormone called glucagon-like peptide-1 (GLP-1) "

- units added after BMI figures, i.e. kg/m²

Section 2

- 'Children and adolescents' section updated to: "Saxenda® should not be used in children and adolescents under 18 years of age. This is because the effects and safety of this medicine have not been studied in this age group. "

- 'Driving and using machines' section updated to:

Saxenda® is unlikely to affect your ability to drive and use machines.

Some patients may feel dizziness when taking Saxenda mainly during the first 3 months of treatment (see section ‘Possible side effects’). If you feel dizziness be extra careful while driving or using machines. If you need any further information, talk to your doctor, pharmacist or nurse.""

Section 3

- sentence update under 'How much to inject': "Your doctor should will instruct you to gradually increase your dose by 0.6 mg usually each week until you reach the recommended dose of 3.0 mg once a day."

Section 4.2:

relocation within Section 4.2 of information on missed doses

Section 4.4

- text added regarding Traceability

- Section heading added for 'Patients with heart failure'. (note: section content unchanged)

- Section heading added for 'Special populations'. (note: section content unchanged)

- Section added for 'Hyperglycaemia in insulin treated patients with diabetes mellitus'. Section content relocated to section 4.4 from section 4.2

Section 4.7.

Text updated to include information on dizziness:

"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."

Section 4.8:

Sentence updated as follows: "Overall, gastrointestinal reactions were the most frequently reported adverse reactions during treatment (67.9%)"

Section 5.1

Deletion of text from section on 'Paediatric population': Studies in the paediatric population are ongoing. Currently available results are too limited to draw conclusions on the efficacy of Saxenda in children.

Section 4: addition of 'delay in the emptying of hte stomach' added as an uncommon side effect

Section 4: Update to the HPRA contact details for hte reporting of side effects

Section 4.8:

(1) addition of uncommon adverse reaction in Table 2 as follows:

'Delayed gastric emptying****

****From controlled phase 2, 3a and 3b clinical trials"

(2) HPRA contact details updated to short version

Section 10: revision of text date updated to "09/2019"

Improved presentation of PIL images

Section 4.4: text update

"Patients with type 2 diabetes mellitus receiving liraglutide in combination with insulin and/or a 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. The addition of Saxenda in patients treated with insulin has not been evaluated."

Section 4.8: addition of text

"Hypoglycaemia in patients with type 2 diabetes mellitus treated with insulin

In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with insulin and liraglutide 3.0 mg/day in combination with diet and exercise and up to 2 OADs, severe hypoglycaemia (requiring third party assistance) was reported by 1.5% of patients treated with liraglutide 3.0 mg/day. In this trial, documented symptomatic hypoglycaemia (defined as plasma glucose ≤3.9 mmol/L accompanied by symptoms) was reported by 47.2% of patients treated with liraglutide 3.0 mg/day and by 51.8% of patients treated with placebo. Among patients concomitantly treated with sulfonylurea, 60.9% of patients treated with liraglutide 3.0 mg/day and 60.0% of patients treated with placebo reported documented symptomatic hypoglycaemic events."

New SPC for new product