Important Safety Information for RYBELSUS^®

Indication and Usage

RYBELSUS^® (semaglutide) tablets 7 mg or 14 mg is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes

Limitations of Use

• RYBELSUS^® is not indicated for use in patients with type 1 diabetes

Important Safety Information cont.

Contraindications

• RYBELSUS^® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS^®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with RYBELSUS^®

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 non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS^®. 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 RYBELSUS^® and initiate appropriate management
• Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials with RYBELSUS^®, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with RYBELSUS^® and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3.0%) 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 RYBELSUS^® 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: There have been postmarketing 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 RYBELSUS^® in patients reporting severe adverse gastrointestinal reactions
• Severe Gastrointestinal Adverse Reactions: Use of RYBELSUS^® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving RYBELSUS^® (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). RYBELSUS^® is not recommended in patients with severe gastroparesis
• Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with RYBELSUS^®. If hypersensitivity reactions occur, discontinue use of RYBELSUS^®, 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, cholelithiasis was reported in 1% of patients treated with RYBELSUS^® 7 mg. Cholelithiasis was not reported in RYBELSUS^® 14 mg or placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
• Pulmonary Aspiration During General Anesthesia or Deep Sedation: RYBELSUS^® delays 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 RYBELSUS^®

Adverse Reactions

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

Drug Interactions

• RYBELSUS^® stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating RYBELSUS^®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
• RYBELSUS^® delays gastric emptying and has the potential to impact the absorption of other oral medications. Closely follow RYBELSUS^® administration instructions when coadministering with other oral medications and consider increased monitoring for medications with a narrow therapeutic index, such as levothyroxine

Use in Specific Populations

• Pregnancy: Available data with RYBELSUS^® are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue RYBELSUS^® 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 RYBELSUS^®, 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 RYBELSUS^®
• Pediatric Use: Safety and effectiveness of RYBELSUS^® have not been established in pediatric patients

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