t the importance of the drug to the mother. In lactating rats, liraglutide was excreted unchanged in milk at concentrations approximately 50% of maternal plasma concentrations.
8.4 Pediatric Use Safety and effectiveness of Victoza have not been established in pediatric patients. Victoza is not recommended for use in pediatric patients.
8.5 Geriatric Use In the Victoza clinical trials, a total of 797 (20%) of the patients were 65 years of age and over and 113 (2.8%) were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment There is limited experience in patients with mild, moderate, and severe renal impairment, including end stage renal disease. Therefore, Victoza should be used with caution in this patient population. No dose adjustment of Victoza is recommended for patients with renal impairment [see Clinical Pharmacology (12.3)].
8.7 Renal Impairment There is limited experience in patients with mild, moderate or severe hepatic impairment. Therefore, Victoza should be used with caution in this patient population. No dose adjustment of Victoza is recommended for patients with hepatic impairment [see Clinical Pharmacology (12.3)].
8.8 Gastroparesis Victoza slows gastric emptying. Victoza has not been studied in patients with pre-existing gastroparesis.
10 OVERDOSAGEIn a clinical trial, one patient with type 2 diabetes experienced a single overdose of Victoza 17.4 mg subcutaneous (10 times the maximum recommended dose). Effects of the overdose included severe nausea and vomiting requiring hospitalization. No hypoglycemia was reported. The patient recovered without complications. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.
11 DESCRIPTIONVictoza contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. The structural formula (Figure 1) is:
Figure 1 Structural Formula of liraglutide
Victoza is a clear, colorless solution. Each 1 mL of Victoza solution contains 6 mg of liraglutide. Each pre-filled pen contains a 3 mL solution of Victoza equivalent to 18 mg liraglutide (free-base, anhydrous) and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection.
12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionLiraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP |
