SEMAGLUTIDE Drug Interactions: What You Need to Know

INTERACTIONS Oral Medications : OZEMPIC delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution ( 7.2 ).

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6 )]</span> .

7.2 Oral Medications OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Nonetheless, caution should be exercised when oral medications are concomitantly administered with OZEMPIC.

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6 )]</span> .

7.2 Oral Medications OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Nonetheless, caution should be exercised when oral medications are concomitantly administered with OZEMPIC.

RYBELSUS and OZEMPIC tablets are 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) [see Warnings and Precautions ( 5.1 )] .
• A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS or OZEMPIC tablets. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with semaglutide tablets [see Warnings and Precautions ( 5.7 )] .
• Personal or family history of MTC or in patients with MEN 2 syndrome type 2 ( 4 )
• Prior serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC ( 4 )

AND PRECAUTIONS

• Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Discontinue if pancreatitis is suspected. ( 5.2 )
• Diabetic Retinopathy Complications: Has been reported in a clinical trial. Patients with a history of diabetic retinopathy should be monitored. ( 5.3 )
• Never share an OZEMPIC pen between patients , even if the needle is changed. ( 5.4 )
• Hypoglycemia: Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin secretagogue or insulin may be necessary. ( 5.5 )
• Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.6 )
• Severe Gastrointestinal Adverse Reactions : Use has been associated with gastrointestinal adverse reactions, sometimes severe. OZEMPIC is not recommended in patients with severe gastroparesis. ( 5.7 )
• Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. Discontinue OZEMPIC if suspected and promptly seek medical advice. ( 5.8 )
• Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. ( 5.9 )
• Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.10 )

5.1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . It is unknown whether OZEMPIC causes thyroid C-cell tumors, including MTC, in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. OZEMPIC 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 OZEMPIC 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 OZEMPIC. Such monitoring may increase the risk of unnecessary procedures, due to the low-test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values &gt;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 Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. After initiation of OZEMPIC, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue OZEMPIC and initiate appropriate management.

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (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 (OZEMPIC 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (OZEMPIC 0.7%, placebo 0.4%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. 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.

5.4 Never Share an OZEMPIC Pen Between Patients OZEMPIC pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 )]</span>. The risk of hypoglycemia may be lowered by a reduction in the dose 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.

5.6 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 experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. Monitor renal function in patients reporting adverse reactions to OZEMPIC that could lead to volume depletion, especially during dosage initiation and escalation of OZEMPIC.

5.7 Severe Gastrointestinal Adverse Reactions Use of OZEMPIC has been associated with gastrointestinal adverse reactions, sometimes severe <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>. In OZEMPIC clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving OZEMPIC (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. OZEMPIC is not recommended in patients with severe gastroparesis.

5.8 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with OZEMPIC. If hypersensitivity reactions occur, discontinue use of OZEMPIC; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to OZEMPIC <span class="opacity-50 text-xs">[see Contraindications ( 4 ), Adverse Reactions ( 6.2 )]</span> . Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with OZEMPIC.

5.9 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 1.5% and 0.4% of patients-treated with OZEMPIC 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

5.10 Pulmonary Aspiration During General Anesthesia or Deep Sedation OZEMPIC delays gastric emptying <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.2 ) ]</span>. 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. Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking OZEMPIC, including whether modifying preoperative fasting recommendations or temporarily discontinuing OZEMPIC could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking OZEMPIC.

5.1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . It is unknown whether OZEMPIC causes thyroid C-cell tumors, including MTC, in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. OZEMPIC 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 OZEMPIC 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 OZEMPIC. Such monitoring may increase the risk of unnecessary procedures, due to the low-test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values &gt;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 Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. After initiation of OZEMPIC, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue OZEMPIC and initiate appropriate management.

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (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 (OZEMPIC 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (OZEMPIC 0.7%, placebo 0.4%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. 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.

5.4 Never Share an OZEMPIC Pen Between Patients OZEMPIC pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 )]</span>. The risk of hypoglycemia may be lowered by a reduction in the dose 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.

5.6 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 experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. Monitor renal function in patients reporting adverse reactions to OZEMPIC that could lead to volume depletion, especially during dosage initiation and escalation of OZEMPIC.

5.8 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with OZEMPIC. If hypersensitivity reactions occur, discontinue use of OZEMPIC; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to OZEMPIC <span class="opacity-50 text-xs">[see Contraindications ( 4 ), Adverse Reactions ( 6.2 )]</span> . Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with OZEMPIC.