Dosing and uses of Victoza, Saxenda (liraglutide)
Adult dosage forms and strengths
SC solution muliti-dose pen
- 18mg/3mL (Victoza); delivers doses of 0.6mg, 1.2mg, or 1.8 mg
- 18mg/3mL (Saxenda); delivers doses of 0.6mg, 1.2mg, 1.8mg, 2.4mg, or 3 mg
Diabetes Mellitus, Type 2
Victoza: 0.6 mg SC qDay for 1 week initially, THEN increase to 1.2 mg qDay
If glycemic control not achieved, can increase to 1.8 mg qDay
Initial dose of 0.6 mg SC qDay is only to decrease GI adverse effects and does not provide glycemic controL
Limitations of use for Victoza
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
- Has not been studied in patients with a history of pancreatitis; consider other antidiabetic therapies in patients with a history of pancreatitis
- Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis
- Has not been studied in combination with prandial insulin
Obesity
Approved by the FDA December 23, 2014
Indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a body mass index (BMI) of ≥30 (obesity) or adults with a BMI of ≥27 (overweight) who have at least 1 weight-related condition (eg, hypertension, type 2 diabetes, dyslipidemia)
Saxenda: Initiate at 0.6 mg SC qDay for 1 week; increase by 0.6 mg/day in weekly intervals until a dose of 3 mg/day is achieved
Limitations of use for Saxenda
- Not indicated for treatment of type 2 diabetes
- Should not be used in combination with any other GLP-1 receptor agonist
- Should not be used with insulin
- Effects on cardiovascular morbidity and mortality have not been established
- Safety and efficacy of coadministration with other products for weight loss have not been established
- Has not been studied in patients with a history of pancreatitis
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Victoza, Saxenda (liraglutide) adverse (side) effects
>10% (Victoza)
Nausea (26%)
Diarrhea (17%)
Vomiting (11%)
>10% (Saxenda)
Nausea (39.3%)
Hypoglycemia in T2DM (23%)
Diarrhea (20.9%)
Constipation (19.4%)
Vomiting (15.7%)
Headache (13.6%)
1-10% (Victoza)
Constipation (10%)
Headache (9%)
Antiliraglutide antibodies (7%)
Injection-site reactions (2%)
1-10% (Saxenda)
Decreased appetite (10%)
Dyspepsia (9.6%)
Fatigue (7.5%)
Dizziness (6.9%)
Abdominal pain (5.4%)
Increased lipase (5.3%)
Upper abdominal pain (5.1%)
Gastroesophageal reflux disease (4.7%)
Gastroenteritis (4.7%)
Abdominal distension (4.5%)
Eructation (4.5%)
Urinary tract infection (4.3%)
Flatulence (4%)
Viral gastroenteritis (2.8%)
Injection site erythema (2.5%)
Injection site reaction (2.5%)
Insomnia (2.4%)
Dry mouth (2.3%)
Asthenia (2.1%)
Anxiety (2%)
<1% (Victoza)
Urticaria
Upper respiratory tract infection
UTI
Dizziness
Sinusitis
Nasopharyngitis
Back pain
Hypertension
Hypoglycemia (mostly in combination therapy)
Pancreatitis
Papillary thyroid carcinoma
Thyroid C-cell hyperplasia
Postmarketing Reports
Dehydration resulting from nausea, vomiting, and diarrhea
Increased serum creatinine, acute renal failure, and worsening chronic renal failure, sometimes requiring hemodialysis
Hypersensitivity reactions (anaphylactic and angioedema)
Allergic reactions: Rash, pruritus
Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis
Warnings
Black box warnings
Causes thyroid C-cell tumors in rodents; human risk could not be determined
Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)
Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with liraglutide
Contraindications
Hypersensitivity
Personal or family history of medullary thyroid carcinoma
Multiple endocrine neoplasia type 2
Pregnancy (Saxenda)
Cautions
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide
Acute gallbladder disease reported
Resting heart rate may increase by 2 to 3 bpm; up to 10-20 bpm increases also reported
Not studied with insulin
Gastrointestinal reactions are the most common reactions
Hepatic impairment
Counsel patients regarding the risk of medullary thyroid carcinoma (MTC) and the symptoms of thyroid tumors; routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with liraglutide; significantly elevated serum calcitonin may indicate MTC; patients with MTC usually have values >50 ng/L; if serum calcitonin is measured and found to be elevated, evaluate patient further; patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated
Renal Impairment reported in association with nausea, vomiting, diarrhea, or dehydration, which may sometimes require hemodialysis; use caution when initiating or escalating doses of in these patients
Lower dose of insulin secretagogue (eg, sulfonylurea) when used in combination, because serious hypoglycemia may result
Use may be associated with weight loss
Not for use in patients with type 1 diabetes mellitus or for treatment of diabetic ketoacidosis
Not a substitute for insulin
Patients with a history of angioedema to other GLP-1 receptor agonists
No studies have evaluated evidence of macrovascular risk reduction
Suicidal ideation (Saxenda)
Never share pen between patients even if needle is changed
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if excreted in human milk; either discontinue drug or nursing
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Victoza, Saxenda (liraglutide)
Mechanism of action
Incretin mimetic; analogue of human glucagonlike peptide-1 (GLP-1); acts as GLP-1 receptor agonist to increase insulin secretion in the presence of elevated blood glucose; delays gastric emptying to decrease postprandial glucose; also decreases glucagon secretion
Absorption
Absolute bioavailability: 55%
Peak plasma time: 8-12 hr
Average steady state concentration over 24 hr: 128 ng/mL (at 1.8 mg dose)
Distribution
Protein bound: >98%
Vd: 13 L (SC); 0.07 L/kg (IV)
Metabolism
Endogenously metabolized to large proteins without a specific organ route
Elimination
Half-life: 13 hr
Mean apparent clearance: 1.2 L/hr (SC)
Excretion (metabolites): 5% feces, 6% urine
Administration
SC Administration
Administer SC in abdomen, thigh, or upper arm; rotate injection site
Administer SC qDay at any time, independent of meals
Injection site and time of administration can be changed without dose adjustment
If dose missed, resume the once-daily regimen with the next scheduled dose; do not give an extra dose or a higher dose; if missed dose more than 3 days, initiate therapy at 0.6 mg/day to avoid GI symptoms
Storage
Store in refrigerator (36-46°F); do not freeze; do not use if frozen
After first use, may store at room temperature (59-86°F) or refrigerate (36-46°F)
Injection pen expires 30 days after first use
