orforglipron 17.2 MG Oral Tablet

INDICATIONS AND USAGE FOUNDAYO TM is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. FOUNDAYO™ is a GLP-1 receptor agonist indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. ( 1 ) Limitations of Use Concomitant use with another GLP-1 receptor agonist is not recommended. ( 1 ) Limitations of Use Concomitant use with another GLP-1 receptor agonist is not recommended.

DOSAGE AND ADMINISTRATION Take FOUNDAYO orally once daily, with or without food. ( 2.1 ) Swallow tablets whole. Do not break, crush, or chew. ( 2.1 ) Do not take more than one tablet per day. ( 2.1 ) Starting dosage is 0.8 mg once daily. After at least 30 days, increase dosage to 2.5 mg once daily. ( 2.1 ) After at least 30 days on the 2.5 mg dosage, increase dosage to 5.5 mg once daily. ( 2.1 ) Dosage may be increased to the next dosage level (9 mg, 14.5 mg, or 17.2 mg once daily) after at least 30 days on the current dosage, based on treatment response and tolerability. ( 2.1 ) Maximum dosage is 17.2 mg once daily. ( 2.1 ) 2.1 Recommended Dosage and Administration Recommended Administration Take FOUNDAYO orally once daily, with or without food. Swallow tablets whole. Do not break, crush, or chew. Do not take more than one tablet per day. Recommended Dosage Escalation Follow the FOUNDAYO starting dosage and escalation described below to reduce the risk of gastrointestinal (GI) adverse reactions [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6 )] . The starting dosage is 0.8 mg orally once daily. After at least 30 days on the 0.8 mg dosage, increase the dosage to 2.5 mg once daily. After at least 30 days on the 2.5 mg dosage, increase the dosage to 5.5 mg once daily. The dosage may be increased to the next dosage level (9 mg, 14.5 mg, or 17.2 mg once daily) after at least 30 days on the current dosage, based on treatment response and tolerability. The maximum dosage of FOUNDAYO is 17.2 mg once daily. 2.2 Dosage Modification for Concomitant Use with CYP3A4 Inhibitors and CYP3A4 Inducers FOUNDAYO dosage modification may be required to manage interactions with some concomitant medications [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . Strong CYP3A4 Inhibitors Avoid strong CYP3A4 inhibitors that also inhibit OATP1B when taking FOUNDAYO. The maximum dosage of FOUNDAYO is 9 mg once daily when used concomitantly with a strong CYP3A4 inhibitor [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . Strong and Moderate CYP3A4 Inducers Avoid strong CYP3A4 inducers when taking FOUNDAYO. Monitor FOUNDAYO effectiveness when concomitantly using moderate CYP3A4 inducers and escalate FOUNDAYO dosage as needed [see Dosage and Administration ( 2.1 , 2.3 ), Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . 2.3 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose. If 7 or more consecutive doses are missed, reinitiate dosage escalation at a lower dosage to reduce the risk of gastrointestinal adverse reactions [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6 )] .

WARNINGS AND PRECAUTIONS Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including FOUNDAYO. Discontinue if pancreatitis is suspected. ( 5.2 ) Severe Gastrointestinal Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. FOUNDAYO is not recommended in patients with severe gastroparesis. ( 5.3 ) Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.4 ) Hypoglycemia: Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing the dosage of insulin or insulin secretagogue may be necessary. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. ( 5.5 ) Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists. If suspected, advise the patient to promptly seek medical attention and discontinue FOUNDAYO. ( 5.6 ) Diabetic Retinopathy Complications in Patients with Type 2 Diabetes: Has not been studied in patients with diabetic retinopathy and/or macular edema requiring acute treatment. Monitor patients with a history of diabetic retinopathy for progression. ( 5.7 ) Acute Gallbladder Disease : Has been reported in clinical trials. If cholecystitis is suspected, gallbladder studies and clinical follow-up are indicated. ( 5.8 ) Pulmonary Aspiration During General Anesthesia and 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. ( 5.9 ) 5.1 Risk of Thyroid C-Cell Tumors In products with GLP-1 receptor agonist activity that are pharmacologically active in rats and mice, rodent thyroid C-cell tumors (adenomas and carcinomas) have been observed at clinically relevant exposures and are considered GLP-1 receptor-dependent effects in rodents. Orforglipron is not pharmacologically active in rats or mice and did not produce tumors in rodents [see Nonclinical Toxicology ( 13.1 )] . While orforglipron is pharmacologically active at the human GLP-1 receptor, the human relevance of GLP-1 receptor-dependent thyroid C-cell tumors observed in rodents has not been determined [see Nonclinical Toxicology ( 13.1 )] . 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. FOUNDAYO 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 FOUNDAYO and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, or persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with FOUNDAYO. 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 values may indicate MTC and patients with MTC usually have calcitonin values >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 has been reported in patients treated with FOUNDAYO. Fatal and non-fatal hemorrhagic or necrotizing pancreatitis have been observed in patients treated with GLP-1 receptor agonists [see Adverse Reactions ( 6 )] . After initiation of FOUNDAYO, 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 FOUNDAYO and initiate appropriate management. 5.3 Severe Gastrointestinal Reactions Use of FOUNDAYO has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients treated with orforglipron (approximately 3%) than patients who received placebo (1%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists [see Adverse Reactions ( 6 )] . FOUNDAYO is not recommended in patients with severe gastroparesis. 5.4 Acute Kidney Injury Due to Volume Depletion There have been reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists or FOUNDAYO. The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions ( 6 )] . Monitor renal function in patients reporting adverse reactions to FOUNDAYO that could lead to volume depletion, especially during dosage initiation and escalation of FOUNDAYO. 5.5 Hypoglycemia FOUNDAYO lowers blood glucose and can cause hypoglycemia. In a trial of adults with type 2 diabetes and BMI ≥27 kg/m 2 (Trial 2), hypoglycemia (plasma glucose <54 mg/dL) was reported in 2% of patients treated with orforglipron versus 0.2% of patients receiving placebo. One patient treated with orforglipron and no patients receiving placebo reported severe hypoglycemia in Trial 2. In Trial 2, 7% of patients treated with orforglipron once daily in combination with sulfonylurea reported hypoglycemia compared with 0.5% of patients not taking a sulfonylurea [see Adverse Reactions ( 6.1 )] . There is also increased risk of hypoglycemia in patients treated with FOUNDAYO in combination with insulin [see Drug Interactions ( 7.2 )] . Hypoglycemia has also been associated with FOUNDAYO and GLP-1 receptor agonists in adults without type 2 diabetes [see Adverse Reactions ( 6.1 )] . Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In patients with diabetes, monitor blood glucose prior to starting FOUNDAYO and during FOUNDAYO treatment. The risk of hypoglycemia may be lowered by a reduction in the dose of insulin or sulfonylurea (or other concomitantly administered insulin secretagogue). 5.6 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists [see Adverse Reactions ( 6.2 )] . If hypersensitivity reactions occur, advise the patient to promptly seek medical attention and discontinue use of FOUNDAYO. FOUNDAYO is contraindicated in patients with a prior serious hypersensitivity reaction to orforglipron or to any of the excipients in FOUNDAYO. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with FOUNDAYO. 5.7 Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Temporary worsening of diabetic retinopathy has been reported with rapid improvement in glucose control. FOUNDAYO has not been studied in patients with diabetic retinopathy and/or macular edema requiring acute treatment. Monitor patients with a history of diabetic retinopathy for progression of diabetic retinopathy. 5.8 Acute Gallbladder Disease Treatment with FOUNDAYO and GLP-1 receptor agonists is associated with an increased occurrence of acute gallbladder disease. In a pool of two clinical trials for weight reduction (Trials 1 and 2), cholelithiasis was reported in 1% of patients treated w

CONTRAINDICATIONS FOUNDAYO is contraindicated in patients with: A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions ( 5.1 )] . Known serious hypersensitivity to orforglipron or any of the excipients in FOUNDAYO. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with GLP-1 receptor agonists [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.2 )] . Personal or family history of MTC or in patients with MEN 2 ( 4 ) Known serious hypersensitivity to orforglipron or any of the excipients in FOUNDAYO ( 4 )

Mechanism of Action FOUNDAYO is a GLP-1 receptor agonist that binds to and activates the human GLP-1 receptor. GLP-1 is a physiological regulator of appetite and caloric intake. GLP-1 receptors are present in brain regions that regulate appetite. In animal studies, orforglipron distributed to and activated neurons in brain regions that regulate appetite and food intake.