WARNING: RISK OF THYROID C-CELL TUMORS

In rodents, Semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Semaglutide causes thyroid C-cell tumors, including Medullary Thyroid Carcinoma (MTC), in humans as human relevance of Semaglutide-induced rodent thyroid C-cell tumors has not been determined.
Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Semaglutide 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 Semaglutide.

General Semaglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Diabetic ketoacidosis has been reported in insulin-dependent patients whom had rapid discontinuation or dose reduction of insulin when treatment with a GLP-1 receptor agonist is started. Gastrointestinal Effects and DehydrationUse of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions that can cause dehydration, which in rare cases can lead to a deterioration of renal function. Patients treated with Semaglutide should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion. Risk of Thyroid C-Cell Tumors Semaglutide Tablet is contraindicated in patients with a personal or family history ofMTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of Semaglutide Tablet 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 Semaglutide Tablet. 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. Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including Semaglutide Tablet. After initiation of Semaglutide Tablet, 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, discontinue Semaglutide Tablet and initiate appropriate management. Diabetic Retinopathy Complications The effect of long-term glycemic control with Semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving Semaglutide Tablet in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia may be lowered by a reduction in the dosage of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. Acute Kidney InjuryThere have been post marketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists, including Semaglutide. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of Semaglutide Tablet in patients reporting severe adverse gastrointestinal reactions.Severe Gastrointestinal Adverse ReactionsUse of Semaglutide Tablet has been associated with gastrointestinal adverse reactions,sometimes severe. Semaglutide Tablet is not recommended in patients with severe gastroparesis.Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with Semaglutide Tablet. If hypersensitivity reactions occur, discontinue use of Semaglutide Tablet; treat promptly per standard of care, and monitor until signs and symptoms resolve.Acute Gallbladder DiseaseAcute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post marketing. If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.Pulmonary Aspiration during General Anesthesia or Deep SedationSemaglutide Tablet delays gastric emptying. There have been rare post marketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Semaglutide Tablet.Hypersensitivity ReactionsSerious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with Semaglutide Tablet. If hypersensitivity reactions occur, discontinue use of Semaglutide Tablet; treat promptly per standard of care, and monitor until signs and symptoms resolve.Heart FailureThere is no therapeutic experience in patients with congestive heart failure and Semaglutide is therefore not recommended in these patients.Effects on ability to drive and use machinesSemaglutide has no or negligible influence on the ability to drive or use machines. However, dizziness can be experienced mainly during dose escalation. Driving or use of machines should be done cautiously if dizziness occurs. When it is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.PregnancySemaglutide should not be used during pregnancy. Women of childbearing potential are recommended to use contraception when treated with Semaglutide. If a patient wishes to become pregnant, or pregnancy occurs, Semaglutide should be discontinued. Semaglutide should be discontinued at least 2 months before a planned pregnancy due to the long half-life.Nursing MothersNo measurable concentrations of Semaglutide were found in breast milk of lactating women. Salcaprozate sodium was present in breast milk and some of its metabolites were excreted in breast milk at low concentrations. As a risk to a breast-fed child cannot be excluded, Semaglutide should not be used during breast-feeding.