Saxenda

Important Administration Instructions

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Prior to initiation of SAXENDA, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.

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Inspect SAXENDA visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.

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Administer SAXENDA in combination with a reduced-calorie diet and increased physical activity.

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Inject SAXENDA subcutaneously once daily at any time of day, without regard to the timing of meals.

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Inject SAXENDA 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 , Adverse Reactions ].

Table 1. Dose Escalation Schedule

 

Adult Patients

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For adults, the recommended dosage of SAXENDA is 3 mg daily, lower dosages are for titration only.

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Discontinue SAXENDA if the patient cannot tolerate the 3 mg dosage.

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If patients do not tolerate an increased dose during dosage escalation, consider delaying dosage escalation for approximately one additional week.

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Evaluate the change in body weight 16 weeks after initiating SAXENDA and discontinue SAXENDA if the patient has not lost at least 4% of baseline body weight, since it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

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In adult patients with type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment.

Pediatric Patients

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For pediatric patients, the recommended maintenance dosage of SAXENDA is 3 mg daily. Pediatric patients who do not tolerate 3 mg daily may have their maintenance dose reduced to 2.4 mg daily. Discontinue SAXENDA if the patient cannot tolerate the 2.4 mg dose.

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If pediatric patients do not tolerate an increased dose during dosage escalation, the dose may also be lowered to the previous level. Dosage escalation for pediatric patients may take up to 8 weeks.

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Evaluate the change in BMI after 12 weeks on the maintenance dose and discontinue SAXENDA if the patient has not had a reduction in BMI of at least 1% from baseline, since it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Pregnancy

Risk Summary

Based on animal reproduction studies, there may be risks to the fetus from exposure to SAXENDA during pregnancy. SAXENDA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Additionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm. When a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, and discontinue SAXENDA (see Clinical Considerations).

Animal reproduction studies identified increased adverse embryofetal 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 3 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 and miscarriage for the indicated populations is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryofetal risk

Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy.

Animal Data

Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison.

Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans 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 exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. 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), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 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 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 exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. 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 liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data).

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SAXENDA and any potential adverse effects on the breastfed infant from SAXENDA 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 SAXENDA as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management have been established in pediatric patients aged 12 years and older with body weight above 60 kg and an initial BMI corresponding to 30 kg/m2 or greater for adults (obese) by international cut-offs. Use of SAXENDA for this indication is supported by a 56-week double-blind, placebo-controlled clinical trial in 251 pediatric patients aged 12 to 17 years, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see Clinical Pharmacology , Clinical Studies ].

In the pediatric clinical trial, there was one death due to suicide in a SAXENDA-treated patient [see Warnings and Precautions ]; one SAXENDA-treated patient had an event of pancreatitis [see Warnings and Precautions ]; more episodes of hypoglycemia confirmed by self blood glucose monitoring occurred in SAXENDA-treated patients compared to placebo [see Warnings and Precautions , Adverse Reactions ]; and mean increases in resting heart rate of 3 to 7 bpm from baseline were observed with SAXENDA-treated patients [see Warnings and Precautions ].

The safety and effectiveness of SAXENDA have not been established in patients less than 12 years of age.

Geriatric Use

In the SAXENDA clinical trials, 232 (6.9%) of the SAXENDA-treated patients were 65 years of age and over, and 17 (0.5%) of the SAXENDA-treated patients 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.

Renal Impairment

There is limited experience with SAXENDA in patients with mild, moderate, and severe renal impairment, including end‑stage renal disease.

Hepatic Impairment

There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, SAXENDA should be used with caution in this patient population [see Clinical Pharmacology ].