Important Safety Information

Contraindications

• Ozempic^® and Rybelsus^® tablets are contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in Ozempic^® or Rybelsus^® tablets. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with semaglutide tablets

Warnings and Precautions

• Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
• Acute Pancreatitis: Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide tablets. Observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back), with or without nausea or vomiting. If pancreatitis is suspected, discontinue Ozempic^® or Rybelsus^® tablets and initiate appropriate management
• Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with semaglutide tablets and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high CV risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
  Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy
• Hypoglycemia: Patients receiving Ozempic^® or Rybelsus^® tablets in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
• Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Ozempic^® or Rybelsus^® tablets that could lead to volume depletion, especially during initiation and escalation of Ozempic^® or Rybelsus^® tablets
• Severe Gastrointestinal (GI) Adverse Reactions: Use of semaglutide tablets has been associated with GI adverse reactions, sometimes severe. In clinical trials, severe GI adverse reactions were reported more frequently among patients who received semaglutide tablets (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). Severe GI adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Ozempic^® and Rybelsus^® tablets are not recommended in patients with severe gastroparesis
• Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with semaglutide tablets. If hypersensitivity reactions occur, discontinue use of Ozempic^® or Rybelsus^® tablets, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
• Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials to improve glycemic control, cholelithiasis was reported in 1% of patients treated with semaglutide tablets 7 mg. In a 4-year CV outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with semaglutide tablets 14 mg and in 0.9% of placebo-treated patients. In Trial 7, cholecystitis was reported in 1.1% treated with semaglutide tablets 14 mg and in 0.7% of placebo-treated patients. If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
• Pulmonary Aspiration During General Anesthesia or Deep Sedation: Ozempic^® and Rybelsus^® tablets delay gastric emptying. There have been rare postmarketing 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 Ozempic^® or Rybelsus^® tablets

Adverse Reactions

• The most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation

Drug Interactions

• Semaglutide stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating Ozempic^® or Rybelsus^® tablets, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
• Semaglutide delays gastric emptying and has the potential to impact the absorption of other oral medications. When using Ozempic^® or Rybelsus^® tablets concomitantly with other oral drugs that have a narrow therapeutic index or that require clinical monitoring, consider increased clinical or laboratory monitoring

Use in Specific Populations

• Pregnancy: Available data with semaglutide use in pregnant women are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue Ozempic^® or Rybelsus^® tablets in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
• Lactation: A clinical lactation study reported semaglutide concentrations below the lower limit of quantification in human breast milk. However, salcaprozate sodium (SNAC) and/or its metabolites are present in human milk. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, an absorption enhancer for Ozempic^® and Rybelsus^® tablets, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with Ozempic^® or Rybelsus^® tablets

Please click here for Ozempic^® and Rybelsus^® tablets Prescribing Information, including Boxed Warning.