Semaglutide Side Effects, Dosing and Safety

FDA Status — Compounded Formulation

Nuvari's semaglutide is dispensed as a compounded formulation prepared by a licensed compounding pharmacy after a physician's evaluation. Compounded semaglutide is not the FDA-approved product (Wegovy®/Ozempic®) and, like all compounded medications, is not reviewed by the FDA for safety, effectiveness, or quality before dispensing. The safety information on this page is drawn from the FDA-approved labeling for semaglutide.

Indications

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition.

Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Known serious hypersensitivity to semaglutide or any of the excipients

Warnings and Precautions

• Thyroid C-cell tumors: Monitor for symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). If MTC is suspected, discontinue semaglutide and refer for evaluation.
• Acute pancreatitis: Has been reported with GLP-1 receptor agonists. Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed.
• Acute gallbladder disease: Events including cholelithiasis and cholecystitis have been reported. If gallbladder disease is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
• Hypoglycemia: Risk is increased when used with insulin secretagogues (e.g., sulfonylureas) or insulin. Consider lowering the dose of the concomitant insulin secretagogue or insulin to reduce the risk.
• Acute kidney injury: Has been reported, usually in association with nausea, vomiting, and diarrhea leading to dehydration. Monitor renal function in patients with renal impairment reporting severe gastrointestinal reactions.
• Diabetic retinopathy complications: Rapid improvement in glucose control may be associated with a temporary worsening of diabetic retinopathy. Monitor patients with a history of diabetic retinopathy.
• Hypersensitivity reactions: Serious reactions including anaphylaxis and angioedema have been reported. Discontinue if suspected and treat promptly.
• Suicidal behavior and ideation: Monitor for depression or suicidal thoughts. Discontinue if symptoms develop.
• Pulmonary aspiration: Semaglutide delays gastric emptying. There is a risk of pulmonary aspiration during procedures requiring general anesthesia or deep sedation. Consider holding semaglutide before scheduled surgeries.

Common Side Effects

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain
• Headache
• Fatigue
• Dyspepsia (indigestion)
• Dizziness
• Abdominal distension
• Eructation (belching)
• Flatulence
• Gastroenteritis
• Gastroesophageal reflux disease

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• Severe, persistent abdominal pain, with or without vomiting (possible pancreatitis)
• A lump or swelling in your neck, hoarseness, difficulty swallowing, or shortness of breath (possible thyroid tumor)
• Signs of allergic reaction: rash, itching, swelling of the face, lips, tongue, or throat, difficulty breathing
• Severe pain in the upper right abdomen (possible gallbladder problems)
• Changes in vision (in patients with diabetes)
• Decreased urination or dark-colored urine (possible kidney problems)
• Rapid heartbeat
• Depression or thoughts of self-harm

Drug Interactions

• Insulin and insulin secretagogues: Increased risk of hypoglycemia. Consider dose reduction of the concomitant insulin or sulfonylurea.
• Oral medications: Semaglutide delays gastric emptying, which may affect the absorption of concomitantly administered oral medications. Monitor the effect of oral medications when initiating or changing the dose of semaglutide.
• Oral contraceptives: Delayed gastric emptying may reduce the efficacy of oral hormonal contraceptives. Patients should use an additional non-oral contraceptive method for 4 weeks after initiation and for 4 weeks after each dose increase.
• Levothyroxine: Semaglutide may increase levothyroxine exposure. Monitor thyroid function.
• Warfarin: Monitor INR when initiating or altering semaglutide therapy in patients taking warfarin.

Use in Specific Populations

• Pregnancy: Contraindicated. Discontinue semaglutide at least 2 months before a planned pregnancy due to the long washout period. May cause fetal harm based on animal studies.
• Lactation: Not recommended during breastfeeding. It is not known whether semaglutide is excreted in human breast milk.
• Pediatric use: Safety and effectiveness have not been established in pediatric patients under 12 years of age.
• Geriatric use: No overall differences in safety or efficacy observed in geriatric patients, though greater sensitivity of some older individuals cannot be ruled out.
• Renal impairment: Monitor renal function in patients with renal impairment reporting gastrointestinal adverse reactions.
• Hepatic impairment: No dose adjustment recommended, though limited data are available for severe hepatic impairment.