OZEMPIC (semaglutide)

There are 4 contraindications. Absolute contraindication.

Contraindication List
Acute pancreatitis
Family history of medullary thyroid carcinoma
Medullary thyroid carcinoma
Multiple endocrine neoplasia type 2

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Gastroparesis

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Diabetic retinopathy
Hypoglycemic disorder
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Kidney disease with reduction in glomerular filtration rate (GFr)

There are 11 severe adverse reactions.

More Frequent	Less Frequent
None.	Biliary calculus Hypoglycemic disorder

Rare/Very Rare
Acute pancreatitis Acute renal failure Anaphylaxis Angioedema Appendicitis Cholecystitis Ileus Kidney disease with reduction in glomerular filtration rate (GFr) Necrotizing pancreatitis

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Constipation Diarrhea Elevated serum amylase Elevated serum lipase Gastroenteritis Headache disorder Nausea Pharyngitis Vomiting	Dyspepsia Eructation Fatigue Flatulence Gastroesophageal reflux disease Tachycardia

Rare/Very Rare
Alopecia Dizziness Dysesthesia Dysgeusia Gastritis Hemorrhoids Hiccups Injection site sequelae Photophobia Skin rash Urticaria

Data are lacking on the use of semaglutide in pregnant women. However, reproduction studies in animals have shown teratogenic effects. Poorly controlled diabetes mellitus during pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortion, preterm delivery, and delivery complications.

In addition, poorly controlled diabetes mellitus during pregnancy increases the risk of major fetal birth defects, stillbirth, and macrosomia-related morbidity. Embryofetal mortality, structural abnormalities (e.g., visceral and skeletal abnormalities), and alterations to growth were observed in the offspring of rats who were administered semaglutide during organogenesis at dosages resulting in systemic exposures lower than the maximum recommended human dosage. In reproduction studies in rabbits and monkeys, early pregnancy loss and structural abnormalities (e.g., visceral and skeletal abnormalities) were observed at dosages below the maximum recommended human dosage and at dosages at least 5 times greater than the maximum recommended human dosage.

Salcaprozate sodium (SNAC), an absorption enhancer contained in semaglutide oral tablets, crosses the placenta and reaches fetal tissues in rats. In a prenatal and postnatal development study in pregnant Sprague Dawley rats, SNAC was administered orally at 1000 mg/kg per day (exposure levels were not measured) on gestation day 7 through lactation day 20. An increase in the length of gestation and number of stillbirths and a decrease in pup viability were observed.

The manufacturers of the semaglutide preparations used for diabetic management state the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Semaglutide should be discontinued in women for at least 2 months before a planned pregnancy due to the drug's long half-life. The manufacturer of the semaglutide preparation used for weight control management states that weight loss offers no benefit to a pregnant patient and may cause fetal harm; if a patient becomes pregnant while receiving the drug, treatment should be discontinued. A pregnancy exposure registry has been established to monitor pregnancy outcomes in women exposed to Wegovy(R); encourage pregnant women exposed to the drug to contact 1-800-727-6500.

Semaglutide is distributed into milk in rats at concentrations 3-12 fold lower than in maternal plasma. It is not known whether semaglutide is distributed into milk in humans or what the effects of the drug are on the breast-fed infant or on milk production. The benefits of breast-feeding and the importance of semaglutide to the woman should be considered along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

SNAC, an absorption enhancer contained in semaglutide oral tablets, and/or its metabolites are concentrated in the milk of lactating rats. SNAC and/or its metabolites were detected in milk of lactating rats following a single maternal administration on lactation day 10. Mean levels of SNAC and/or its metabolites in milk were approximately 2-12 fold higher than in maternal plasma.

There are no data on the presence of SNAC in human milk; however, substances present in animal milk are likely to be present in human milk. Since the activity of UGT2B7, an enzyme involved in SNAC clearance, is lower in infants than in adults, higher SNAC plasma concentrations may occur in neonates and infants. Because of the unknown potential for serious adverse reactions in the breast-fed infant due to the possible accumulation of SNAC from breast-feeding and because there are alternative formulations of semaglutide (e.g., injection) that can be used during lactation, patients should be advised that breast-feeding is not recommended during treatment with oral semaglutide.

In the pool of placebo- and active-controlled glycemic control clinical trials, 23.6% of patients receiving subcutaneous semaglutide and 29.9% of those receiving oral semaglutide were 65 years of age and older; 3.2%

of those receiving subcutaneous semaglutide and 4.8% of those receiving oral semaglutide were 75 years of age and older. In a cardiovascular outcome trial (SUSTAIN-6) of subcutaneous semaglutide, 48% of patients were 65 years of age and older and 9.6%

were 75 years of age and older; in a cardiovascular outcomes trial of oral semaglutide (PIONEER 6), 43.4 or 12.3% of patients were at least 65 or at least 75 years of age, respectively.

In the trials of subcutaneous semaglutide (Wegovy), 8.8% of patients receiving the drug were 65-75 years of age and 0.9% were >=75 years of age. No substantial differences in safety and efficacy relative to younger adults were observed in these patients, but increased sensitivity in some geriatric individuals cannot be ruled out.