Reasons for adding or updating:

• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.8 - Undesirable effects
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 22-Sep-2016

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The following sections of the SmPC have been updated:


2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

One 1 ml of solution contains 6 mg of liraglutide*. One pre­filled pen contains 18 mg liraglutide in 3 ml.

 ...

            4.8       Undesirable effects

...

Table 1           Adverse reactions from long-term controlled phase 3 trials and spontaneous (postmarketing) reports

 

MedDRA system organ classes	Very common	Common	Uncommon	Rare	Very rare
Infections and infestations		Nasopharyngitis Bronchitis
Immune system disorders				Anaphylactic reactions
Metabolism and nutrition disorders		Hypoglycaemia Anorexia Appetite decreased	Dehydration
Nervous system disorders		Headache Dizziness
Cardiac disorders		Increased heart rate
Gastrointestinal disorders	Nausea Diarrhoea	Vomiting Dyspepsia Abdominal pain upper Constipation Gastritis Flatulence Abdominal distension Gastroesophageal reflux disease Abdominal discomfort Toothache		Intestinal obstruction	Pancreatitis (including necrotising pancreatitis)
Skin and subcutaneous tissue disorder		Rash	Urticaria Pruritus
Renal and urinary disorders			Renal impairment Renal failure acute
General disorders and administration site conditions		Fatigue Injection site reactions	Malaise
Investigations		Increased lipase* Increased amylase*

* From controlled phase 3b and 4 clinical trials only where they were measured.

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 Date of first authorisation: 30 June /06/2009

Date of last renewal: 11 April /04/2014

 

10.       DATE OF REVISION OF THE TEXT

 05/201609/2016

 

 

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 26-May-2016

Legal Category:POM

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The SmPC has had updates in the following sections:

• 4.1. with additional text for Monotherapy administration
• 4.2 for use in patients with mild or moderate hepatic impairment
• 5.1 with addition of Monotherapy results for HbA_1c and for Proportion of Patients achieving reductions in HbA_1c
• 5.1 with merging of tables 2-5 into table 2

Track change details below:

4.1       Therapeutic indications

Victoza is indicated for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control as:

Monotherapy

When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance or contraindications.

Combination therapy

 Iin combination with oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control (see sections 4.4 and 5.1 for available data on the different combinations).

4.2       Posology and method of administration

….

Hepatic impairment

The therapeutic experience in patients with all degrees of hepatic impairment is currently too limited to recommend the use in patients with mild, moderate or severe hepatic impairmentNo dose adjustment is required for patients with hepatic impairmentNo dose adjustment is recommended for patients with mild or moderate hepatic impairment. Victoza is not recommended for use in patients with severe hepatic impairment  (see section 5.2).

 

5.1       Pharmacodynamic properties

…

GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not entirely clear. In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions involved in regulation of appetite, where liraglutide via specific activation of the GLP-1 receptorR (GLP-1R), increased key satiety and decreased key hunger signals, thereby leading to lower body weight.

….

Clinical efficacy and safety

….

These trials included 3,978 exposed patients with type 2 diabetes (2,501 patients treated with Victozaliraglutide), 53.7% men and 46.3% women, 797 patients (508 treated with liraglutide) were ≥65 years of age and 113 patients (66 treated with liraglutide) were ≥75 years of age.

….

 •          Glycaemic control

 

Monotherapy

Liraglutide monotherapy for 52 weeks resulted in statistically significant and sustained reductions in HbA_1c for both 1.2 mg and 1.8 mg (p=0.0014, p<0.0001, respectively)compared with glimepiride 8 mg (-0.84% for 1.2 mg, -1.14% for 1.8 mg vs -0.51% for comparator) in patients previously treated with either diet and exercise or OAD monotherapy at no more than half-maximal dose (Table 2).

 

Combination with oral antidiabetics

Liraglutide in combination therapy, for 26 weeks, with metformin, glimepiride or metformin and rosiglitazone resulted in statistically significant (p<0.0001) and sustained reductions in HbA_1c compared with patients receiving placebo (Tables 2to 5).

 

Combination with metformin

Table 2            Victoza^® Liraglutide in monotherapy (52 weeks) and in combination with oral antidiabetics

(26 weeks)

	N	Mean baseline HbA1c (%)	Mean HbA1c change from baseline (%)	Patients (%) achieving HbA1c<7%	Mean baseline weight (kg)	Mean weight change from baseline (kg)
Monotherapy
Liraglutide 1.2 mg	251	8.182	-0.84*	42.8061, 58.383	92.1	-2.05**
Liraglutide 1.8 mg	246	8.19	-1.14**	50.91, 62.03	92.6	-2.45**
Glimepiride1 8 mg/day	248	8.23	-0.51	27.81, 30.883	93.3	1.12
Add-on to metformin 2(2,000 mg/day)
Liraglutide 1.2 mg	240	8.3	-0.97†	35.361, 52.872	88.5	-2.58**
Liraglutide 1.8 mg	242	8.4	-1.00†	42.461, 66.372	88.0	-2.79**
Placebo	121	8.4	0.09	10.81, 22.572	91.0	-1.51
Glimepeiride3 4 mg/day	242	8.4	-0.98	36.361, 56.072	89.0	0.95
Add-on to glimepiride 3(4 mg/day)
Liraglutide 1.2 mg	228	8.5	-1.08**	34.561, 57.472	80.0	0.32**
Liraglutide 1.8 mg	234	8.5	-1.13**	41.661, 55.972	83.0	-0.23**
Placebo	114	8.4	0.23	7.561, 11.872	81.9	-0.10
Rosiglitazone4 4 mg/day	231	8.4	-0.44	21.916, 36.172	80.6	2.11
Add-on to metformin 2(2,000 mg/day) + rosiglitazone 5(4 mg twice daily)
Liraglutide 1.2 mg	177	8.48	-1.48	57.561	95.3	-1.02
Liraglutide 1.8 mg	178	8.566	-1.48	53.761	94.9	-2.02
Placebo	175	8.42	-0.54	28.161	98.5	0.60
Add-on to metformin 2(2,000 mg/day) + glimepiride 3(4 mg/day)
Liraglutide 1.2	N/A
Liraglutide 1.8 mg	230	8.3	-1.33*	53.161	85.8	-1.81**
Placebo	114	8.3	-0.24	15.361	85.4	-0.42
Insulin glargine94	232	8.1	-1.09	45.861	85.2	1.62

^{1glimepiride 8 mg/day; 2metformin 2,000 mg/day; 3glimepiride 4 mg/day; 4}rosiglitazone 4 mg/day,⁵rosiglitazone 4 mg twice daily
^*Superiority (p<0.01) vs. active comparator; **Superiority (p<0.0001) vs. active comparator; ^†Non-inferiority (p<0.0001) vs. active comparator

¹⁶all patients; ⁷²previous OAD monotherapy; ⁸³previous diet treated patients
⁹⁴the dosing of insulin glargine was open-labelled and was applied according to Guideline for titration of insulin glargine. Titration of the insulin glargine dose was managed by the patient after instruction by the investigator:

2Table 2  Victoza in combination with metformin (26 weeks)

Metformin add-on therapy	1.8 mg liraglutide + metformin2	1.2 mg liraglutide + metformin2	Placebo + metformin2	Glimepiride1 + metformin2
N	242	240	121	242
Mean HbA1c (%)      Baseline      Change from baseline	8.4 -1.00	8.3 -0.97	8.4 0.09	8.4 -0.98
Patients (%) achieving HbA1c <7%      All patients      Previous OAD monotherapy	42.4 66.3	35.3 52.8	10.8 22.5	36.3 56.0
Mean body weight (kg)      Baseline      Change from baseline	88.0 -2.79	88.5 -2.58	91.0 -1.51	89.0 0.95

¹ glimepiride 4 mg/day; ² metformin 2,000 mg/day

 

Combination with sulfonylurea

Table 3     Victoza in combination with glimepiride (26 weeks)

Glimepiride add-on therapy	1.8 mg liraglutide + glimepiride2	1.2 mg liraglutide + glimepiride2	Placebo + glimepiride2	Rosiglitazone1 + glimepiride2
N	234	228	114	231
Mean HbA1c (%)      Baseline      Change from baseline	8.5 -1.13	8.5 -1.08	8.4 0.23	8.4 -0.44
Patients (%) achieving HbA1c <7%      All patients      Previous OAD monotherapy	41.6 55.9	34.5 57.4	7.5 11.8	21.9 36.1
Mean body weight (kg)      Baseline      Change from baseline	83.0 -0.23	80.0 0.32	81.9 -0.10	80.6 2.11

¹ Rosiglitazone 4 mg/day; ² glimepiride 4 mg/day

 

Combination with thiazolidinedione and metformin

Table 4           Victoza in combination with metformin + rosiglitazone (26 weeks)

Metformin + rosiglitazone add-on therapy	1.8 mg liraglutide + metformin1 + rosiglitazone2	1.2 mg liraglutide + metformin1 + rosiglitazone2	Placebo + metformin1 + rosiglitazone2	N/A
N	178	177	175
Mean HbA1c (%)      Baseline      Change from baseline	8.56 -1.48	8.48 -1.48	8.42 -0.54
Patients (%) achieving HbA1c <7%      All patients	53.7	57.5	28.1
Mean body weight (kg)      Baseline      Change from baseline	94.9 -2.02	95.3 -1.02	98.5 0.60

¹ Metformin 2,000 mg/day; ² rosiglitazone 4 mg twice daily

 

Combination with sulfonylurea and metformin

Table 5           Victoza in combination with glimepiride + metformin (26 weeks)

Metformin + glimepiride add-on therapy	1.8 mg liraglutide + metformin2 + glimepiride3	N/A	Placebo + metformin2 + glimepiride3	Insulin glargine1 + metformin2 + glimepiride3
N	230		114	232
Mean HbA1c (%)      Baseline      Change from baseline	8.3 -1.33		8.3 -0.24	8.1 -1.09
Patients (%) achieving HbA1c <7%      All patients	53.1		15.3	45.8
Mean body weight (kg)      Baseline      Change from baseline	85.8 -1.81		85.4 -0.42	85.2 1.62

^{1 The dosing of insulin glargine was open-labelled and was applied according to the following titration guideline. Titration of the insulin glargine dose was managed by the patient after instruction by the investigator. 2 Metformin 2,000 mg/day; 3 glimepiride 4 mg/day.}

Guideline for titration of insulin glargine

Self-measured FPG	Increase in insulin glargine dose (IU)
≤5.5 mmol/l (≤100 mg/dl) Target	No adjustment
>5.5 and <6.7 mmol/l (>100 and <120 mg/dl)	0–2 IUa
≥6.7 mmol/l (≥120 mg/dl)	2 IU

^aAccording to the individualised recommendation by the investigator at the previous visit, for example depending on whether the patient has experienced hypoglycaemia.

 

Combination with insulin

 

Use in patients with renal impairment

In a double-blind trial comparing the efficacy and safety of liraglutide 1.8 mg versus placebo as add-on to insulin and/or OAD in patients with type 2 diabetes and moderate renal impairment, liraglutide was superior to placebo treatment in reducing HbA_1c after 26 weeks (–1.05% vs –0.38%). Significantly more patients achieved HbA_1c below 7% with liraglutide compared with placebo (52.8% vs 19.5%). In both groups a decrease in body weight was seen: –2.4 kg with liraglutide vs –1.09 kg with placebo. There was a comparable risk of hypoglycaemic episodes between the two treatment groups. The safety profile of liraglutide was generally similar to that observed in other studies with liraglutide.

 

•          Proportion of patients achieving reductions in HbA_1c

Liraglutide alone resulted in a statistically significant (1.8mg p < 0.0001, 1.2mg p = 0.0025)greater proportion of patients achieving HbA_1c ≤6.5% at 52 weeks compared with patients receiving glimepiride (37.6% for 1.8 mg and 28.0% for 1.2 mg vs 16.2% for comparator).

 

Liraglutide in combination with metformin, glimepiride, or metformin and rosiglitazone resulted in a statistically significant (p≤0.0001) greater proportion of patients achieving an HbA_1c ≤6.5% at 26 weeks compared with patients receiving these agents alone.

 

•          Fasting plasma glucose

Treatment with liraglutide alone or and in combination with one or two oral antidiabetic drugs resulted in a reduction in fasting plasma glucose of 13­43.5 mg/dl (0.72­2.42 mmol/l). This reduction was observed within the first two weeks of treatment.

             ….

 

•          Body weight

Liraglutide alone and in combination with metformin, metformin and glimepiride or metformin and rosiglitazone was associated with sustained weight reduction over the duration of trials in a range from 1.0 kg to 2.8 kg.

….

Renal impairment:

Liraglutide exposure was reduced in patients with renal impairment compared to individuals with normal renal function. Liraglutide exposure was lowered by 33%, 14%, 27% and 2826%, respectively, in patients with mild (creatinine clearance, CrCl 50-80 ml/min), moderate (CrCl 30­50 ml/min), and severe (CrCl <30 ml/min) renal impairment and in end‑stage renal disease requiring dialysis, respectively.

….

10.       DATE OF REVISION OF THE TEXT

 

05/2016

 

 

 

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 25-Feb-2016

Legal Category:POM

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4.         CLINICAL PARTICULARS

4.2       Posology and method of administration

Patients with rRenal impairment

No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 60–90 ml/min and 30–59 ml/min, respectively). There is no therapeutic experience in patients with severe renal impairment (creatinine clearance below 30 ml/min). Victoza can currently not be recommended for use in patients with severe renal impairment including patients with end­stage renal disease (see section 5.2).

 

Patients with hHepatic impairment

The therapeutic experience in patients with all degrees of hepatic impairment is currently too limited to recommend the use in patients with mild, moderate or severe hepatic impairment (see section 5.2).

 

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic properties

Other clinical data

In an open label trial comparing the efficacy and safety of liraglutide 1.8 mg with lixisenatide 20 mcg in 404 patients inadequately controlled on metformin therapy (mean HbA_1c 8.4%), liraglutide was superior to lixisenatide in reducing HbA_1c after 26 weeks of treatment (-1.83% vs. -1.21%, p<0.0001). Significantly more patients achieved HbA_1c below 7% with liraglutide compared to lixisenatide (74.2% vs. 45.5%, p<0.0001), as well as the HbA_1c target below or equal 6.5% (54.6% vs. 26.2%, p<0.0001). Significantly greater reduction in fasting plasma glucose was achieved with liraglutide than lixisenatide (-2.85 vs. -1.70 mmol/l, p<0.0001).Body weight loss was observed in both treatment arms (-4.3 kg with liraglutide and ‑3.7 kg with lixisenatide). The safety profile of liraglutide and lixisenatide was overall comparable. Gastrointestinal adverse events were more frequently reported with liraglutide treatment (43.6% vs. 37.1%). No new safety information was identified with liraglutide.

 

10.       DATE OF REVISION OF THE TEXT

02/2016

 

Reasons for adding or updating:

• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Sep-2015

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Changes:

 

 

5.1      Pharmacodynamic properties

 

Sentence added:

 

GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not entirely clear. In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions involved in regulation of appetite, where liraglutide via specific activation of the GLP-1R, increased key satiety and decreased key hunger signals, thereby leading to lower body weight.

 

 

10.      DATE OF REVISION OF THE TEXT

 

09/2015

Reasons for adding or updating:

• Change to section 4.9 - Overdose
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 19-Mar-2015

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Black Triangle (CHM): NO

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4.9      Overdose

From clinical trials and marketed use, overdoses have been reported of up to 40 times (72 mg) the recommended maintenance dose. Generally, the patients Events reported included severe nausea, and severe vomiting and diarrhoea. None of the patients reported severe included hypoglycaemia. All patients recovered without complications.

10. DATE OF REVISION OF THE TEXT
03/2015

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 19-Dec-2014

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4.2      Posology and method of administration

 

sulphonylurea changed to sulfonylurea

 

Patients with renal impairment

Wording changed to:

No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 60–90 ml/min and 30–59 ml/min, respectively). There is no therapeutic experience in patients with severe renal impairment (creatinine clearance below 30 ml/min). Victoza can currently not be recommended for use in patients with   severe renal impairment including patients with end­stage renal disease (see section 5.2).

  

4.4      Special warnings and precautions for use

Wording changed to:

Acute pancreatitis

Use of GLP-1 receptor agonists has been associated with a risk of developing acute pancreatitis. There have been few reported events of acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Victoza should be discontinued; if acute pancreatitis is confirmed, Victoza should not be restarted. Caution should be exercised in patients with a history of pancreatitis

 

4.8      Undesirable effects

Wording changed to:

Patients >70 years may experience more gastrointestinal effects when treated with liraglutide.

Patients with mild and moderate renal impairment (creatinine clearance 60­90 ml/min and 30–59 ml/min, respectively) may experience more gastrointestinal effects when treated with liraglutide.

 

5.1      Pharmacodynamic properties

Sentences added:

Additional trials were conducted with liraglutide that included 1,901 patients in four unblinded randomised, controlled clinical trials (including 464, 658, 323 and 177 subjects per trial) and one double-blind, randomised, controlled clinical trial in subjects with type 2 diabetes and moderate renal impairment (279 patients).

 

Use in patients with renal impairment

In a double-blind trial comparing the efficacy and safety of liraglutide 1.8 mg versus placebo as add-on to insulin and/or OAD in patients with type 2 diabetes and moderate renal impairment, liraglutide was superior to placebo treatment in reducing HbA_1c after 26 weeks (–1.05% vs –0.38%). Significantly more patients achieved HbA_1c below 7% with liraglutide compared with placebo (52.8% vs 19.5%). In both groups a decrease in body weight was seen: –2.4 kg with liraglutide vs –1.09 with placebo. There was a comparable risk of hypoglycaemic episodes between the two treatment groups. The safety profile of liraglutide was generally similar to that observed in other studies with liraglutide.

 

Renal impairment:

Sentence added:

Similarly, in a 26-week clinical trial, patients with type 2 diabetes and moderate renal impairment (CrCL 30-59 ml/min, see section 5.1) had 26% lower liraglutide exposure when compared with a separate trial including patients with type 2 diabetes with normal renal function or mild renal impairment

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Last renewal date added:

Date of last renewal: 11/04/2014

 

 

 

10.      DATE OF REVISION OF THE TEXT

Revision date changed to

12/2014

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.7 - Effects on ability to drive and use machines
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 28-Apr-2014

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4.1 Therapeutic indications

Victoza is indicated for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control:In combination with:

Inserted text in bold: “oral glucose-lowering medicinal products and/or basal insulin when these,together with diet and exercise, do not provide adequate glycaemic control (see sections 4.4 and 5.1 for available data on the different combinations)”.

 

Deleted:– Metformin or a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea.

In combination with:

– Metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with

insufficient glycaemic control despite dual therapy.

 

4.2      Posology and method of administration

Text in bold added:

Victoza can be added to existing sulphonylurea or to a combination of metformin and sulphonylurea therapy or a basal insulin. When Victoza is added to sulphonylurea therapy or basal insulin, a reduction in the dose of sulphonylurea or basal insulin should be considered to reduce the risk of hypoglycaemia (see section 4.4).

 

Self-monitoring of blood glucose is not needed in order to adjust the dose of Victoza. However, when initiating treatment with Victoza in combination with a sulphonylurea or a basal insulin, blood glucose self-monitoring may become necessary to adjust the dose of the sulphonylurea or the basal insulin.

 

4.4      Special warnings and precautions for use

Liraglutide is not a substitute for insulin.

Text deleted:The addition of liraglutide in patients already treated with insulin has not been evaluated and is therefore not recommended.

 

Hypoglycaemia

Text in bold added:

Patients receiving liraglutide in combination with a sulphonylurea or a basal insulin may have an increased risk of hypoglycaemia (see section 4.8). The risk of hypoglycaemia can be lowered by a reduction in the dose of sulphonylurea or basal insulin.

 

4.7      Effects on ability to drive and use machines

Text in bold added:

Victoza has no or negligible influence on the ability to drive and use machines.

Patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines, in particular when Victoza is used in combination with a sulphonylurea or a basal insulin.

 

4.8      Undesirable effects

Hypoglycaemia

Text in bold added:

The risk of hypoglycaemia is low with combined use of basal insulin and liraglutide (1.0 events per subject year, see section 5.1).

 

5.1      Pharmacodynamic properties

Clinical study information added.

 

10.      DATE OF REVISION OF THE TEXT

Text in bold added:

 04/2014

Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 11-Mar-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

4.8 Undesirable effects

Adverse reaction - Pancreatitis (including necrotising pancreatitis) - Spontaneous reports - Very rare

Cardiac disorders
Adverse reaction - Increased heart rate - Spontaneous reports - Not known

10. Date of Revision of the Text
03/2013

Reasons for adding or updating:

• Removal of black triangle

Date of revision of text on the SPC: 29-Oct-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Removal of Black Triangle Symbol

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects
• Change to section 4.9 - Overdose
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 23-Oct-2012

Legal Category:POM

Black Triangle (CHM): YES

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In section 4.8 Allergic reactions updated
Allergic reactions including urticaria, rash and pruritus have been reported from marketed use of Victoza. Few cases of anaphylactic reactions with additional symptoms such as hypotension, palpitations, dyspnoea, oedema have been reported with marketed use of Victoza.

In section 4.9 Overdose information updated

From clinical trials and marketed use overdoses have been reported up to 40 times the recommended maintenance dose (72 mg). Events reported included severe nausea and severe vomiting. None of the reports included severe hypoglycaemia. All patients recovered without complications.

In section 10. Date of Revision of Text updated
10/2012

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC: 01-May-2012

Legal Category:POM

Black Triangle (CHM): YES

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Table 1 in 4.8 has been amended to show Malaise listed with uncommon spotaneous reports. Also the wording was changed under Pancreatitis to 'Pancreatitis was also reported post-marketing'.

Reasons for adding or updating:

• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 20-Apr-2012

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Black Triangle (CHM): YES

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In Section  5.1  Pharmacodynamic properties, has been updated to include this Clinical data.

 

Other clinical data

 

In an open label study comparing the efficacy and safety of Victoza (1.2 mg and 1.8 mg) and sitagliptin (a DPP-4 inhibitor, 100 mg) in patients inadequately controlled on metformin therapy (mean HbA_1c 8.5%), Victoza at both doses was statistically superior to sitagliptin treatment in reducing HbA_1c after 26 weeks (‑1.24%, ‑1.50% vs ‑0.90%, p<0.0001). Patients treated with Victoza had a significant decrease in body weight compared to that of patients treated with sitagliptin (‑2.9 kg and ‑3.4 kg vs ‑1.0 kg, p<0.0001). Greater proportions of patients treated with Victoza experienced transient nausea vs subjects treated with sitagliptin (20.8% and 27.1% for liraglutide vs. 4.6% for sitagliptin). The reductions in HbA_1c and superiority vs sitagliptin observed after 26 weeks of Victoza treatment (1.2 mg and 1.8 mg) were sustained after 52 weeks of treatment (‑1.29% and ‑1.51% vs ‑0.88%, p<0.0001). Switching patients from sitagliptin to Victoza after 52 weeks of treatment resulted in additional and statistically significant reduction in HbA_1c (‑0.24% and ‑0.45%, 95% CI: ‑0.41 to ‑0.07 and -0.67 to ‑0.23 ) at week 78, but a formal control group was not available.

Date In Section 10 is: 04/2012

Reasons for adding or updating:

• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 02-Mar-2012

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Black Triangle (CHM): YES

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In section 5.1 (Pharmacodynamic Properties) Clinical data has been added

Other clinical data

In an open label study comparing the efficacy and safety of Victoza 1.8 mg once daily and exenatide 10 mcg twice daily in patients inadequately controlled on metformin and/or sulphonylurea therapy (mean HbA_1c 8.3%), Victoza was statistically superior to exenatide treatment in reducing HbA_1c after 26 weeks (–1.12% vs –0.79%; estimated treatment difference: –0.33; 95% CI –0.47 to –0.18). Significantly more patients achieved HbA_1c below 7% with Victoza compared with exenatide (54.2% vs 43.4%, p=0.0015). Both treatments resulted in mean body weight loss of approximately 3 kg. Switching patients from exenatide to Victoza after 26 weeks of treatment resulted in an additional and statistically significant reduction in HbA_1c (-0.32%, 95% CI: -0.41 to -0.24) at week 40, but a formal control group was not available. During the 26 weeks, there were 12 serious events in 235 patients (5.1%) using liraglutide, whereas there were 6 serious adverse events in 232 patients (2.6%) using exenatide. There was no consistent pattern with respect to system organ class of events.

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC: 23-Nov-2011

Legal Category:POM

Black Triangle (CHM): YES

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4.8 Undesirable effects

The change concerns an update of the product information to include the term ‘urticaria’ in section 4.8 describing spontaneous reports, reflecting postmarketing surveillance reports and a recommendation by the internal Victoza^â safety committee.

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.6 - Pregnancy and Lactation
• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 10-Nov-2011

Legal Category:POM

Black Triangle (CHM): YES

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4.1 Special warnings and precautions for use

Text added:

Victoza is not a substitute for insulin.

The addition of liraglutide in patients already treated with insulin has not been evaluated and is therefore not recommended.

4.5 Interaction with other medicinal products and other forms of interaction.

 

Under Insulin  text added:

 

No pharmacokinetic or pharmacodynamic interactions were observed between liraglutide and insulin detemir when administering a single dose of insulin detemir 0.5 U/kg with liraglutide 1.8 mg at steady state in patients with type 2 diabetes.

4.6 Word Fertility added to Pregnancy and lactation sentence.

 

Fertility

 

 

 

Apart from a slight decrease in the number of live implants, animal studies did not indicate harmful effects with respect to fertility.

 

 

 

5.1 Pharmacodynamic properties

Text added:
In a 52 week clinical trial, the addition of insulin detemir to Victoza® 1.8 mg and metformin in patients not achieving glycemic targets on Victoza® and metformin alone, resulted in a HbA1c decrease from baseline of 0.54%, compared to 0.20% in the Victoza® 1.8 mg and metformin control group. Weight loss was sustained. There was a small increase in the rate of minor hypoglycaemic episodes (0.23 versus 0.03 events per subject years). The addition of liraglutide in patients already treated with insulin has not been evaluated (see section 4.4).

10. Date of revision of text
11/2011

 

 

 

 

 

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC: 30-Dec-2010

Legal Category:POM

Black Triangle (CHM): YES

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4.4 Special warnings and precautions for use

Use of other GLP-1 analogues has been associated with the risk of pancreatitis. There have been few reported events of acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, Victoza and other potentially suspect medicinal products should be discontinued.

Sentence added: Sign and symptoms of dehydration, including altered renal function have been reported in patients treated with Victoza. Patients treated with Victoza should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion

Reasons for adding or updating:

• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 29-Jan-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



10. DATE OF REVISION OF THE TEXT

01/2010

Reasons for adding or updating:

• New SPC for new product

Legal Category:POM

Black Triangle (CHM): YES