What are the black box warnings, contraindications, common adverse drug events (ADEs), and necessary patient education for Rybelsus (semaglutide), including potential drug-to-drug interactions and recommended follow-up intervals?

From the Guidelines

Rybelsus (oral semaglutide) carries a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), and is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2, as well as in those with hypersensitivity to semaglutide, based on the most recent evidence from 1. The medication is also contraindicated in pregnancy. Common adverse drug events include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Decreased appetite
• Constipation with gastrointestinal effects being most prominent during initial therapy and typically diminishing over time, as reported in 1. Patient education should emphasize taking Rybelsus on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day. Patients should be informed about the risk of hypoglycemia, particularly when used with insulin or insulin secretagogues like sulfonylureas, which may require dose adjustments of these medications, as noted in 1. Rybelsus may interact with medications that require rapid gastrointestinal absorption or have narrow therapeutic indices, such as warfarin, levothyroxine, and oral contraceptives, potentially requiring closer monitoring. The medication can also delay gastric emptying, affecting the absorption of oral medications. Patients should be monitored for signs of pancreatitis, kidney injury, hypersensitivity reactions, and diabetic retinopathy complications. Follow-up is typically recommended 1-3 months after initiation to assess tolerability and glycemic response, with subsequent visits every 3-6 months to monitor efficacy, side effects, and potential dose adjustments, based on the guidance from 1. It is essential to note that Rybelsus should not be used with other GLP-1 RAs or with dipeptidyl peptidase-4 inhibitors, and caution is advised when using GLP-1 RAs in combination with insulin or insulin secretagogues, as stated in 1.

From the FDA Drug Label

Black Box Warning: Thyroid C-cell tumors: OZEMPIC 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).

Contraindications:

• A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Known hypersensitivity to semaglutide or to any of the product components

Common Adverse Drug Events (ADEs):

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Injection site reactions

Patient Education:

• Counsel patients regarding the potential risk for MTC with the use of OZEMPIC and inform them of symptoms of thyroid tumors
• Instruct patients to use a different injection site each week when injecting in the same body region
• Inform patients of the risk of hypoglycemia when used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin

Drug-to-Drug Interactions:

• Insulin secretagogues (e.g., sulfonylureas): increased risk of hypoglycemia
• Insulin: increased risk of hypoglycemia
• Oral medications: potential delay of gastric emptying and impact on absorption

Follow-up Intervals:

• Patients should be monitored regularly for signs and symptoms of pancreatitis, thyroid C-cell tumors, and hypoglycemia
• Follow-up intervals should be individualized based on patient-specific factors, such as medical history and concomitant medications 2, 2, 2

Key Points:

• Black Box Warning: Thyroid C-cell tumors
• Contraindications: Personal or family history of MTC or MEN 2, known hypersensitivity to semaglutide
• Common ADEs: Gastrointestinal symptoms, injection site reactions
• Patient Education: Risk of MTC, hypoglycemia, proper injection technique
• Drug-to-Drug Interactions: Insulin secretagogues, insulin, oral medications
• Follow-up Intervals: Regular monitoring for signs and symptoms of pancreatitis, thyroid C-cell tumors, and hypoglycemia

From the Research

Black Box Warnings and Contraindications

• There is no specific mention of black box warnings for Rybelsus (semaglutide) in the provided studies 3, 4, 5, 6, 7.
• Contraindications for Rybelsus are not explicitly stated in the given evidence, but it is indicated for use in patients with type 2 diabetes who require improved glycemic control and are not interested in injectable therapy 5.

Adverse Drug Events (ADEs) and Patient Education

• Common adverse events associated with semaglutide include gastrointestinal disturbances such as nausea and diarrhea 4, 6.
• Patients should be educated on the potential risks of hypoglycemia, particularly when used in combination with other glucose-lowering therapies, including insulin 4, 6.
• Patients with a history of pancreatitis or pancreatic cancer should be monitored closely, as the risk of these conditions is still being studied 4.
• Patients with diabetic retinopathy should be carefully monitored, as semaglutide may increase the risk of complications 4.

Common Side Effects

• Gastrointestinal side effects such as nausea and diarrhea are the most frequently reported adverse events 4, 6.
• Other potential side effects include hypoglycemia, pancreatitis, and pancreatic cancer, although the risk of these conditions is still being studied 4.

Follow-up Intervals

• The recommended follow-up interval for patients taking Rybelsus is not explicitly stated in the provided studies.
• However, patients should be monitored regularly for glycemic control, weight changes, and potential adverse events such as hypoglycemia and gastrointestinal disturbances 4, 6.

Drug-to-Drug Interactions

• Rybelsus may be used in combination with other glucose-lowering therapies, including insulin, but the risk of hypoglycemia should be carefully monitored 4, 6.
• There is no specific mention of other potential drug-to-drug interactions in the provided studies 3, 4, 5, 6, 7.