DIAVORIN

6 mg liraglutide daily. 2 mg. 8 mg to further improve glycaemic control. 8 mg are not recommended. 4). Combination therapy with sulfonylurea is only valid for adult patients. Self-monitoring of blood glucose is not needed in order to adjust the dose of Diavorin .

Blood glucose self-monitoring is necessary to adjust the dose of sulfonylurea and insulin, particularly when Diavorin therapy is started and insulin is reduced. A stepwise approach to insulin dose reduction is recommended. 2). Renal impairment No dose adjustment is required for patients with mild, moderate or severe renal impairment.

2). Hepatic impairment No dose adjustment is recommended for patients with mild or moderate hepatic impairment. 2). Paediatric population No dose adjustment is required for adolescents and children aged 10 years and above. 2). Method of administration Diavorin must not be administered intravenously or intramuscularly.

Diavorin 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 Diavorin is injected around the same time of the day, when the most convenient time of the day has been chosen.

6.

Summary of the safety profile In five large long-term clinical phase 3a trials over 2,500 adult patients have received treatment with Diavorin alone or in combination with metformin, a sulfonylurea (with or without metformin) or metformin plus rosiglitazone.

The most frequently reported adverse reactions during clinical trials were gastrointestinal disorders: nausea and diarrhoea were very common, whereas vomiting, constipation, abdominal pain, and dyspepsia were common. At the beginning of the therapy, these gastrointestinal adverse reactions may occur more frequently.

These reactions usually diminish within a few days or weeks on continued treatment. Headache and nasopharyngitis were also common. Furthermore, hypoglycaemia was common, and very common when liraglutide is used in combination with a sulfonylurea.

Severe hypoglycaemia has primarily been observed when combined with a sulfonylurea. Tabulated list of adverse reactions Table 1 lists adverse reactions reported in long-term phase 3a controlled trials, the LEADER trial (a long-term cardiovascular outcome trial) and spontaneous (post- marketing) reports.

Frequencies for all events have been calculated based on their incidence in phase 3a clinical trials.

Frequencies 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); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1 Adverse reactions from long-term controlled phase 3a trials, the long-term cardiovascular outcome trial (LEADER) and spontaneous (post-marketing) 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 Dizzines s Dysgeusia Cardiac disorders Increased heart rate Gastrointestina l disorders Nausea Diarrho ea Vomiting Dyspepsia Abdominal pain upper Constipation Gastritis Flatulence Abdominal distension Gastroesophageal reflux disease Delayed gastric emptyin g Intestinal obstruction Pancreatitis (including necrotising pancreatitis) Abdominal discomfort Toothache Hepatobiliary disorders Cholelithiasis Cholecystitis 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.

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. 2). There is no therapeutic 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.

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 Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. 1). Thyroid disease Thyroid adverse events, such as goitre, have been reported in clinical trials and in particular in patients with pre-existing thyroid disease.

Liraglutide should therefore be used with caution in these patients. 8). The risk of hypoglycaemia can be lowered by a reduction in the dose of sulfonylurea or 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. Excipients Diavorin contains less than 1 mmol sodium (23 mg) per dose, therefore the medicinal product is essentially ‘sodium-free’.

This medicine contains 42 mg propylene glycol in each 3 ml pre-filled multidose pen which is equivalent to 14 mg/ml. If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

1.