VICTOZA- liraglutide injection
Novo Nordisk
WARNING: RISK OF THYROID C-CELL TUMORS
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Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether VICTOZA causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1)].
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VICTOZA is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of VICTOZA and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with VICTOZA [see Contraindications (4) and Warnings and Precautions (5.1)].
1 INDICATIONS AND USAGE
VICTOZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
1.1 Important Limitations of Use
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VICTOZA is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans. Prescribe VICTOZA only to patients for whom the potential benefits are considered to outweigh the potential risk [see Warnings and Precautions (5.1)].
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Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been observed in patients treated with VICTOZA. VICTOZA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using VICTOZA. Other antidiabetic therapies should be considered in patients with a history of pancreatitis.
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VICTOZA is not a substitute for insulin. VICTOZA should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
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The concurrent use of VICTOZA and prandial insulin has not been studied.
2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
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Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
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Inject VICTOZA subcutaneously in the abdomen, thigh or upper arm. No dose adjustment is needed if changing the injection site and/or timing.
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When using VICTOZA with insulin, administer as separate injections. Never mix.
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It is acceptable to inject VICTOZA and insulin in the same body region but the injections should not be adjacent to each other.
2.2 General Dosing and Administration
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Inject VICTOZA subcutaneously once-daily at any time of day, independently of meals.
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Initiate VICTOZA with a dose of 0.6 mg per day for one week. The 0.6 mg dose is a starting dose intended to reduce gastrointestinal symptoms during initial titration, and is not effective for glycemic control. After one week at 0.6 mg per day, the dose should be increased to 1.2 mg. If the 1.2 mg dose does not result in acceptable glycemic control, the dose can be increased to 1.8 mg. If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase in dose to make up for the missed dose.
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If more than 3 days have elapsed since the last VICTOZA dose, reinitiate VICTOZA at 0.6 mg to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. Upon reinitiation, VICTOZA should be titrated at the discretion of the prescriber.
2.3 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
When initiating VICTOZA, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycemia [see Warnings and Precautions (5.4) and Adverse Reactions (6)].
2.4 Dosage in Patients with Renal Impairment
No dose adjustment is recommended for patients with renal impairment.
3 DOSAGE FORMS AND STRENGTHS
Injection: 6 mg/mL solution in a pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg.
4 CONTRAINDICATIONS
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Medullary Thyroid Carcinoma
VICTOZA is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
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Hypersensitivity
VICTOZA is contraindicated in patients with a prior serious hypersensitivity reaction to VICTOZA or to any of the product components.
5 WARNINGS AND PRECAUTIONS
5.1 Risk of Thyroid C-cell Tumors
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical Toxicology (13.1)]. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether VICTOZA will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
Cases of MTC in patients treated with VICTOZA have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and VICTOZA use in humans.
VICTOZA is contraindicated in patients with a personal or family history of MTC or in patients
with MEN 2. Counsel patients regarding the potential risk for MTC with the use of VICTOZA and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with VICTOZA. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
5.2 Pancreatitis
Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with VICTOZA. After initiation of VICTOZA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, VICTOZA should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, VICTOZA should not be restarted. Consider antidiabetic therapies other than VICTOZA in patients with a history of pancreatitis.
DESCRIPTION
VICTOZA 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 C172 H265 N43 O51 and the molecular weight is 3751.2 Daltons
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Liraglutide 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 (cAMP) leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying.
How Supplied
VICTOZA is available in the following package sizes containing disposable, pre-filled, multi-dose pens. Each individual pen delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg (6 mg/mL, 3 mL).
2 x VICTOZA pen NDC 0169-4060-12
3 x VICTOZA pen NDC 0169-4060-13
Each VICTOZA pen is for use by a single patient. A VICTOZA pen must never be shared between patients, even if the needle is changed.
16.2 Recommended Storage
Prior to first use, VICTOZA should be stored in a refrigerator between 36�F to 46�F (2�C to 8�C) (Table 12). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze VICTOZA and do not use VICTOZA if it has been frozen.
After initial use of the VICTOZA pen, the pen can be stored for 30 days at controlled room temperature (59�F to 86�F; 15�C to 30�C) or in a refrigerator (36�F to 46�F; 2�C to 8�C). Keep the pen cap on when not in use. VICTOZA should be protected from excessive heat and sunlight. Always remove and safely discard the needle after each injection and store the VICTOZA pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy. Always use a new needle for each injection to prevent contamination.
