Victoza

Recommended Dosage

Adult Patients

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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 gastrointestinal symptoms [see Adverse Reactions (6.1)] during initial titration and is not effective for glycemic control in adults.

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After one week at the 0.6 mg once daily dosage, increase the dosage to 1.2 mg injected subcutaneously once daily.

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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

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The recommended starting dosage of VICTOZA is 0.6 mg injected subcutaneously once daily.

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If additional glycemic control is required, increase the dosage in 0.6 mg increments after at least one week on the current dosage.

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The maximum recommended dosage is 1.8 mg injected subcutaneously once daily.

Recommendations Regarding Missed Dose

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Instruct patients who miss a dose of VICTOZA to resume the once -daily dosage regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase the 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 once daily to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. Upon reinitiation, VICTOZA should be titrated at the discretion of the healthcare provider.

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 once daily at any time of day, independently of meals.

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Inject VICTOZA subcutaneously in the abdomen, thigh or upper arm. No dosage adjustment is needed if changing the injection site and/or timing.

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Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis [see Adverse Reactions ].

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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.

Pregnancy

Risk Summary

Based on animal reproduction studies, there may be risks to the fetus from exposure to VICTOZA during pregnancy. VICTOZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data].

The estimated background risk of major birth defects for women with uncontrolled pre-gestational diabetes (Hemoglobin A1C >7) is 6 to 10%. The major birth defect rate has been reported to be as high as 20 to 25% in women with a Hemoglobin A1C >10. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

Animal Data

Female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the human exposure at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.

Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the human exposure at the MRHD of 1.8 mg/day at all doses, based on plasma AUC. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), ≥ 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), ≥ 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group.

In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times human exposure at the MRHD of 1.8 mg/day, based on plasma AUC. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group.

Lactation

Risk Summary

There are no data on the presence of VICTOZA in human milk, the effects on the breastfed infant, or the effects on milk production. Liraglutide was present in milk of lactating rats [see Data].

Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VICTOZA and any potential adverse effects on the breastfed infant from VICTOZA or from the underlying maternal condition.

Data

In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations.

Pediatric Use

The safety and effectiveness of VICTOZA as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients 10 years of age and older. Use of VICTOZA for this indication is supported by a 26-week placebo-controlled clinical trial and a 26-week open-label extension in 134 pediatric patients 10 to 17 years of age with type 2 diabetes mellitus, a pediatric pharmacokinetic study, and studies in adults with type 2 diabetes mellitus [see Clinical Pharmacology and Clinical Studies ]. The risk of hypoglycemia was higher with VICTOZA in pediatric patients regardless of insulin and/or metformin use [see Adverse Reactions ].

The safety and effectiveness of VICTOZA have not been established in pediatric patients less than 10 years of age.

Geriatric Use

In the VICTOZA treatment arms of the glycemic control trials, a total of 832 (19.3%) of the patients were 65 to 74 years of age and 145 (3.4%) were 75 years of age and over [see Clinical Studies ]. In the VICTOZA treatment arm of the LEADER trial [see Clinical Studies ( 14.3)], a total of 1738 (37.2%) patients were 65 to 74 years of age, 401 (8.6%) were 75 to 84 years of age, and 17 (0.4%) were 85 years of age or older at baseline.

No overall differences in safety or effectiveness for VICTOZA have been observed between patients 65 years of age and older and younger patients.

Renal Impairment

No dose adjustment of VICTOZA is recommended for patients with renal impairment [see Clinical Pharmacology ]. The safety and efficacy of VICTOZA was evaluated in a 26-week clinical study that included patients with moderate renal impairment (eGFR 30 to 60 mL/min/1.73m2) [see Clinical Studies ].

In the VICTOZA treatment arm of the LEADER trial [see Clinical Studies ( 14.3)], 1932 (41.4%) patients had mild renal impairment, 999 (21.4%) patients had moderate renal impairment and 117 (2.5%) patients had severe renal impairment at baseline. No overall differences in safety or efficacy were seen in these patients compared to patients with normal renal function.

There is limited experience with VICTOZA in patients with end stage renal disease. There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis [see Warnings and Precautions and Adverse Reactions ]. Use caution in patients who experience dehydration.

Hepatic 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 ].

Gastroparesis

VICTOZA slows gastric emptying. VICTOZA has not been studied in patients with pre-existing gastroparesis.