Victoza

• •
  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 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 ]

  . 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.

  ), Nonclinical Toxicology (

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1, and 3 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1.8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1 and the 3 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice. A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

  A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats.

  Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) proto-oncogene in thyroid C-cells.

  Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by clinical studies or nonclinical studies

  [see Boxed Warning, Warnings and Precautions ]

  .

  Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative in repeat-dose

  in vivo

  micronucleus tests in rats.

  In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide, males were treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1 mg/kg/day, a high dose yielding an estimated systemic exposure 11- times the human exposure at the MRHD, based on plasma AUC. In female rats, an increase in early embryonic deaths occurred at 1 mg/kg/day. Reduced body weight gain and food consumption were observed in females at the 1 mg/kg/day dose.

  )].
• •
  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 CONTRAINDICATIONS

  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)
    [see Warnings and Precautions ]
    .
  • •serious hypersensitivity reaction to liraglutide or to any of the excipients in VICTOZA. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with VICTOZA
    [see Warnings and Precautions (
    5.7
    )].

  • •Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. (4)
  • •Patients with a serious hypersensitivity reaction to liraglutide or any of the excipients in VICTOZA. (4)

  ), 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 ]

  . 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.

  )].

Indications and Usage (

•  Severe Gastrointestinal Adverse Reactions (
  5.6 Severe Gastrointestinal Adverse Reactions

  Use of GLP-1 receptor agonists, including liraglutide, has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions ]

  . In VICTOZA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving VICTOZA (1.2 mg 4.4%, 1.8 mg 4.2%) than placebo (1.1%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. VICTOZA is not recommended in patients with severe gastroparesis.
  ) 10/2025
  
  Pulmonary Aspiration During General Anesthesia
  
  or Deep Sedation (
  5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation

  VICTOZA delays gastric emptying

  [see Clinical Pharmacology (

  12.2

  )]

  . There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

  Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking VICTOZA, including whether modifying preoperative fasting recommendations or temporarily discontinuing VICTOZA could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking VICTOZA.
  )…………………………...……………11/2024

VICTOZA is indicated:

• •as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus,
• •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.

•  
  • •
    Adult Patients
    : Initiate at 0.6 mg injected subcutaneously once daily for one week then increase to 1.2 mg daily. If additional glycemic control is required, increase the dose to 1.8 mg daily after one week of treatment with the 1.2 mg daily dose. (
    2.1 Recommended Dosage

    Adult Patients

    • •The recommended starting dosage of VICTOZA is 0.6 mg injected subcutaneously once daily for one week. The 0.6 mg once daily dosage is intended to reduce the risk of gastrointestinal adverse reactions
      [see Warnings and Precautions , Adverse Reactions ]
      during initial titration and is not effective for glycemic control in adults.
    • •After one week at the 0.6 mg once daily dosage, increase the dosage to 1.2 mg injected subcutaneously once daily.
    • •If additional glycemic control is required, increase the dosage to the maximum recommended dosage of 1.8 mg injected subcutaneously once daily after at least one week of treatment with the 1.2 mg once daily dosage.

    Pediatric Patients Aged 10 Years and Older

    • •The recommended starting dosage of VICTOZA is 0.6 mg injected subcutaneously once daily.
    • •If additional glycemic control is required, increase the dosage in 0.6 mg increments after at least one week on the current dosage, to reduce the risk of gastrointestinal adverse reactions
      [see Warnings and Precautions , Adverse Reactions ]
      .
    • •The maximum recommended dosage is 1.8 mg injected subcutaneously once daily.
    )
  • •
    Pediatric Patients
    : Initiate at 0.6 mg injected subcutaneously once daily for at least one week. If additional glycemic control is required increase the dose to 1.2 mg daily and if additional glycemic control is still required, increase the dose to 1.8 mg daily after at least one week of treatment with the 1.2 mg daily dose. (
    2.1 Recommended Dosage

    Adult Patients

    • •The recommended starting dosage of VICTOZA is 0.6 mg injected subcutaneously once daily for one week. The 0.6 mg once daily dosage is intended to reduce the risk of gastrointestinal adverse reactions
      [see Warnings and Precautions , Adverse Reactions ]
      during initial titration and is not effective for glycemic control in adults.
    • •After one week at the 0.6 mg once daily dosage, increase the dosage to 1.2 mg injected subcutaneously once daily.
    • •If additional glycemic control is required, increase the dosage to the maximum recommended dosage of 1.8 mg injected subcutaneously once daily after at least one week of treatment with the 1.2 mg once daily dosage.

    Pediatric Patients Aged 10 Years and Older

    • •The recommended starting dosage of VICTOZA is 0.6 mg injected subcutaneously once daily.
    • •If additional glycemic control is required, increase the dosage in 0.6 mg increments after at least one week on the current dosage, to reduce the risk of gastrointestinal adverse reactions
      [see Warnings and Precautions , Adverse Reactions ]
      .
    • •The maximum recommended dosage is 1.8 mg injected subcutaneously once daily.
    )
  • •Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles. (
    2.3 Important Administration Instructions

    • •Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
    • •Inject VICTOZA subcutaneously once daily at any time of day, independently of meals.
    • •Inject VICTOZA subcutaneously in the abdomen, thigh or upper arm. No dosage adjustment is needed if changing the injection site and/or timing.
    • •Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis
      [see Adverse Reactions ].
    • •When using VICTOZA with insulin, administer as separate injections. Never mix. It is acceptable to inject VICTOZA and insulin in the same body region but the injections should not be adjacent to each other.
    )
  • •Inject VICTOZA subcutaneously once-daily at any time of day, independently of meals, in the abdomen, thigh or upper arm. (
    2.3 Important Administration Instructions

    • •Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
    • •Inject VICTOZA subcutaneously once daily at any time of day, independently of meals.
    • •Inject VICTOZA subcutaneously in the abdomen, thigh or upper arm. No dosage adjustment is needed if changing the injection site and/or timing.
    • •Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis
      [see Adverse Reactions ].
    • •When using VICTOZA with insulin, administer as separate injections. Never mix. It is acceptable to inject VICTOZA and insulin in the same body region but the injections should not be adjacent to each other.
    )
  • •When using VICTOZA with insulin, administer as separate injections. Never mix. (
    2.3 Important Administration Instructions

    • •Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
    • •Inject VICTOZA subcutaneously once daily at any time of day, independently of meals.
    • •Inject VICTOZA subcutaneously in the abdomen, thigh or upper arm. No dosage adjustment is needed if changing the injection site and/or timing.
    • •Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis
      [see Adverse Reactions ].
    • •When using VICTOZA with insulin, administer as separate injections. Never mix. It is acceptable to inject VICTOZA and insulin in the same body region but the injections should not be adjacent to each other.
    )

Injection: 18 mg/3 mL (6 mg/mL) clear, colorless solution in a prefilled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg.

Pregnancy: VICTOZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (