Liraglutide

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). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-4 and NEP.

Inject Liraglutide subcutaneously in the abdomen, thigh, or upper arm once daily at any time of day, without regard to the timing of meals. The recommended dose of Liraglutide is 3 mg daily. Initiate at 0.6 mg per day for one week. In weekly intervals, increase the dose until a dose of 3 mg is reached. If pediatric patients do not tolerate an increased dose during dose escalation, the dose may also be lowered to the previous level. Dose escalation for pediatric patients may take up to 8 weeks. Pediatric patients who do not tolerate 3 mg daily may have their dose reduced to 2.4 mg daily. Adult patients with type 2 diabetes should monitor blood glucose prior to starting Liraglutide and during Liraglutide treatment.

Pediatric Use: The safety and effectiveness of Liraglutide 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.

Liraglutide causes a delay of gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Liraglutide.

• Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type-2.
• Hypersensitivity to liraglutide or any excipients in Liraglutide.
• Pregnancy

Most common adverse reactions, reported in greater than or equal to 5% are: nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia, and gastroenteritis

Liraglutide is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. There are no available data with liraglutide in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Liraglutide should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Liraglutide should be discontinued.

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

Acute Pancreatitis: Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed.
Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.
Hypoglycemia: This can occur in adults when Liraglutide is used with an insulin secretagogue (e.g. a sulfonylurea) or insulin. The risk may be lowered by a reduction in the dose of concomitantly administered insulin secretagogues or insulin. In the pediatric clinical trial, patients did not have type 2 diabetes. Hypoglycemia occurred in Liraglutide-treated pediatric patients. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
Heart Rate Increase: Monitor heart rate at regular intervals.
Renal Impairment: Has been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration which may sometimes require hemodialysis. Use caution when initiating or escalating doses of Liraglutide in patients with renal impairment.
Hypersensitivity Reactions: Postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema). Discontinue Liraglutide and other suspect medications and promptly seek medical advice.
Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue Liraglutide if symptoms develop.

Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea, severe vomiting and severe hypoglycemia. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.

GLP-1 receptor agonists

Store between 2-8°C. Do not freeze. After initial use, it can be stored between 15-30°C for 30 days. Protect from heat and light.