saxenda

Important safety information

Thyroid C-cell Tumors: See Boxed Warning ( 5.1 ). • Acute Pancreatitis: Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed ( 5.2 ). • Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated ( 5.3 ). • Hypoglycemia: Can occur in adults when SAXENDA 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 SAXENDA-treated pediatric patients. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia ( 2 , 5.4 ). • Heart Rate Increase: Monitor heart rate at regular intervals ( 5.5 ). • 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 SAXENDA in patients with renal impairment ( 5.6 ). • Hypersensitivity Reactions: Postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema). Discontinue SAXENDA and other suspect medications and promptly seek medical advice ( 5.7 ). • Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue SAXENDA if symptoms develop ( 5.8 ). 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 ( 13.1 )] . Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether SAXENDA 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 liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. SAXENDA 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 SAXENDA 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 SAXENDA. 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 greater than 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. 5.2 Acute Pancreatitis Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of SAXENDA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, SAXENDA should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, SAXENDA should not be restarted. In SAXENDA clinical trials in adults, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 SAXENDA-treated patients and 2 (0.1%) of 1843 placebo-treated patients. In addition, there were 2 cases of acute pancreatitis in SAXENDA-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose. There were 2 additional cases in SAXENDA-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing SAXENDA, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days. In a SAXENDA pediatric clinical trial, pancreatitis was not independently adjudicated. Pancreatitis was reported in 1 (0.8%) SAXENDA-treated patient and resulted in treatment discontinuation. Liraglutide has been studied in a limited number of adult patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on SAXENDA. 5.3 Acute Gallbladder Disease In SAXENDA clinical trials in adults, 2.2% of SAXENDA-treated patients reported adverse events of cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in SAXENDA-treated patients versus 0.4% in placebo-treated patients. The majority of SAXENDA-treated patients with adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in SAXENDA-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated. 5.4 Hypoglycemia Adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia with use of SAXENDA, including severe hypoglycemia. In patients with type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment [see Dosage and Administration ( 2 ) and Adverse Reactions ( 6.1 )] . The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In the pediatric clinical trial, patients did not have type 2 diabetes but were provided with blood glucose meters. Clinically significant hypoglycemia, defined as blood glucose <54 mg/dL, occurred in 1.6% of the SAXENDA- treated patients compared to 0.8% of placebo-treated patients [see Adverse Reactions ( 6.1 )]. Inform all pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. 5.5 Heart Rate Increase Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in SAXENDA-treated adult patients compared to placebo in clinical trials. More patients treated with SAXENDA, compared with placebo, had changes from baseline at two consecutive visits of more than 10 bpm (34% versus 19%, respectively) and 20 bpm (5% versus 2%, respectively). At least one resting heart rate exceeding 100 bpm was recorded for 6% of SAXENDA-treated patients compared with 4% of placebo-treated patients, with this occurring at two consecutive study visits for 0.9% and 0.3%, respectively. Tachycardia was reported as an adverse reaction in 0.6% of SAXENDA-treated patients and in 0.1% of placebo-treated patients. In a clinical pharmacology trial that monitored heart rate continuously for 24 hours, SAXENDA treatment was associated with a heart rate that was 4 to 9 bpm higher than that observed with placebo. In a pediatric clinical trial, mean increases from baseline in resting heart rate of 3 to 7 bpm were observed with SAXENDA treatment. Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform health care providers of…