Victoza

/ Novo Nordisk

Posology: To improve gastro-intestinal tolerability, the starting dose is 0.6 mg liraglutide daily. After at least one week, the dose should be increased to 1.2 mg. Some patients are expected to benefit from an increase in dose from 1.2 mg to 1.8 mg and based on clinical response, after at least one week, the dose can be increased to 1.8 mg to further improve glycaemic control. Daily doses higher than 1.8 mg are not recommended. Liraglutide can be added to existing metformin or to a combination of metformin and thiazolidinedione therapy. The current dose of metformin and thiazolidinedione can be continued unchanged. Liraglutide can be added to existing sulfonylurea or to a combination of metformin and sulfonylurea therapy or a basal insulin. When Liraglutide is added to sulfonylurea therapy or basal insulin, a reduction in the dose of sulfonylurea or basal insulin should be considered to reduce the risk of hypoglycaemia. Self-monitoring of blood glucose is not needed in order to adjust the dose of Liraglutide However, when initiating treatment with Liraglutide in combination with a sulfonylurea or a basal insulin, blood glucose self-monitoring may become necessary to adjust the dose of the sulfonylurea or the basal insulin.
Special populations
Elderly patients (>65 years old): No dose adjustment is required based on age.
Renal impairment: No dose adjustment is required for patients with mild, moderate or severe renal impairment. There is no therapeutic experience in patients with end- stage renal disease, and Victoza is therefore not recommended for use in these patients.
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 impairment.
Paediatric population: The safety and efficacy of Liraglutide in children and adolescents below age 18 have not been established. No data are available.
Method of administration: Liraglutide must not be administered intravenously or intramuscularly. Liraglutide is administered once daily at any time, independent of meals, and can be injected subcutaneously in the abdomen, in the thigh or in the upper arm. The injection site and timing can be changed without dose adjustment. However, it is preferable that Liraglutide is injected around the same time of the day, when the most convenient time of the day has been chosen.
See prescribing information for full details.

Victoza® is indicated for:
– Treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise:
1. As monotherapy when metformin is considered inappropriate due to intolerance or contraindications.
2. In addition to other medicinal products for the treatment of diabetes.
– To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.

Hypersensitivity to the active substance or to any of the excipients. 

Liraglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.Liraglutide is not a substitute for insulin. There is limited experience in patients with congestive heart failure New York Heart Association (NYHA) class III and liraglutide should therefore be used with caution. There is no experience in patients with congestive heart failure NYHA class III-IV and liraglutide is therefore not recommended in these patients. 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.
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, Liraglutide should be discontinued; if acute pancreatitis is confirmed, Liraglutide should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Thyroid disease: Thyroid adverse events, including increased blood calcitonin, goitre and thyroid neoplasm have been reported in clinical trials in particular in patients with preexisting thyroid disease and liraglutide should therefore be used with caution.
Hypoglycaemia: Patients receiving liraglutide in combination with a sulfonylurea or a basal insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia can be lowered by a reduction in the dose of sulfonylurea or basal insulin.
Dehydration: Signs and symptoms of dehydration, including renal impairment and acute renal failure have been reported in patients treated with liraglutide. 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.

Nasopharyngitis Bronchitis, Hypoglycaemia, Anorexia, Appetite decreased, Increased heart rate, Vomiting, Dyspepsia, Abdominal pain upper, Constipation, Gastritis. Flatulence, Abdominal distension, Gastroesophageal reflux disease, Abdominal discomfort, Toothache, Fatigue, Injection site reactions.
See prescribing information for full details.

In vitro, liraglutide has shown very low potential to be involved in pharmacokinetic interactions with other active substances related to cytochrome P450 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. 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 with 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 INR (International Normalised Ratio) is recommended.
Paracetamol: Liraglutide did not change the overall exposure of paracetamol following a single dose of 1000 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 to a clinically relevant degree 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 adjustment of digoxin dose 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 ethinyloestradiol 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 ethinyloestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to be unaffected when co-administered with liraglutide.
Insulin: 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.

Pregnancy: There are no adequate data from the use of liraglutide in pregnant women.
Lactation: It is not known whether liraglutide is excreted in human milk.
See prescribing information for full details.           

From clinical trials and marketed use, overdoses have been reported of up to 40 times (72 mg) the recommended maintenance dose. Generally, the patients reported severe nausea, vomiting and diarrhoea. None of the patients reported 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.

Storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Store away from the freezer compartment.
After first use: Store below 30°C or store in a refrigerator (2°C – 8°C). Do not freeze.
Compatibility: Substances added to liraglutide may cause degradation of liraglutide. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.