b'Bleed Size: 8.125Trim Size: 7.875major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respec-tively. Clinical Considerations: Disease-associated maternal and/or embryo/fetal risk: Appropriate weight gain based on pre-pregnancy weight is currently recom-mended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy. Data: Animal Data: In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.04-, 0.1-, and 0.4-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure. In an embryofetal development study in pregnant rabbits, subcuta-neous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.01-, 0.1-, and 0.9-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormali-ties were observed at greater than or equal to 0.0025 mg/kg/day, at clinically relevant exposures. In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.4-, 2-, and 6-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at greater than or equal to 0.075 mg/kg twice weekly (greater than or equal to 2 times human exposure). In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.2-, 1-, and 3-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at greater than or equal to 0.075 mg/kg twice weekly (greater than or equal to 1 time human exposure). Lactation: Risk Summary: There are no data on the presence of semaglutide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk (see Data). The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for WEGOVY and any potential adverse effects on the breastfed infant from WEGOVY or from the underlying maternal condition. Data: In lactating rats, Bleed Size:Trim Size:semaglutide was detected in milk at levels 3-12 fold lower than in maternal plasma. Females and Males of Reproductive Potential: Because of the potential for 11 10.75 fetal harm, discontinue WEGOVY in patients at least 2 months before they plan to become pregnant to account for the long half-life of semaglutide [see Use in Specific Populations]. Pediatric Use: Safety and efficacy of WEGOVY have not been established in pediatric patients. Geriatric Use: In the WEGOVY clinical trials, 233 (8.8%) WEGOVY-treated patients were between 65 and 75 years of age and 23 (0.9%) WEGOVY-treated patients were 75 years of age and over. No overall differences in safety or efficacy were detected between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment: No dose adjustment of WEGOVY is recommended for patients with renal impairment. In a study in subjects with renal impairment, including end-stage renal disease, no clinically relevant change in semaglutide pharmacokinetics was observed. Hepatic Impairment: No dose adjustment of WEGOVY is recom -mended for patients with hepatic impairment. In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide phar-macokinetics was observed. OVERDOSAGE: Overdoses have been reported with other GLP-1 receptor agonists.More detailed information is available upon request. Effects have included severe nausea, severe vomiting, and severe hypoglycemia.Manufactured by: Novo Nordisk A/S In the event of overdose, appropriate supportive treatment should be initiatedDK-2880 Bagsvaerd according to the patients clinical signs and symptoms. A prolonged period of obse-r Denmarkvation and treatment for these symptoms may be necessary, taking into account thelong half-life of WEGOVY of approximately 1 week. For information about WEGOVYcontact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536 1-833-934-6891Date of Issue: June 2021 Version: 1WEGOVY and Ozempic are registered trademarks of Novo Nordisk A/S.PATENT INFORMATION:http://www.novonordisk-us.com/products/product-patents.html 2022 Novo NordiskAll rights reserved. US22SEMO0071510/2022'