INTERACTIONS Oral Medications: Delays gastric emptying and has the potential to reduce the rate of absorption of concomitantly administered oral medications ( 7.1 , 12.3 ).
7.1 Oral Medications TRULICITY delays gastric emptying and thus has the potential to reduce the rate of absorption of concomitantly administered oral medications. The delay in gastric emptying is dose-dependent but is attenuated with the recommended dose escalation to higher doses of TRULICITY <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span> . The delay is largest after the first dose and diminishes with subsequent doses. In clinical pharmacology studies, TRULICITY 1.5 mg did not affect the absorption of the tested orally administered medications to a clinically relevant degree <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . There is limited experience with the use of concomitant medications in clinical trials with TRULICITY doses of 3 mg and 4.5 mg. Monitor drug levels of oral medications with a narrow therapeutic index (e.g., warfarin) when concomitantly administered with TRULICITY.
7.2 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin When initiating TRULICITY, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )]</span>.
TRULICITY is contraindicated in patients with: 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 )] . Serious hypersensitivity reaction to dulaglutide or to any of the product components. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with TRULICITY [see Warnings and Precautions ( 5.4 )] . Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 ( 4 , 5.1 ). Patients with a serious hypersensitivity reaction to dulaglutide or any of the product components ( 4 , 5.4 ).
AND PRECAUTIONS Thyroid C-cell Tumors: See Boxed Warning ( 5.1 ).
Acute
Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including TRULICITY. Discontinue if pancreatitis is suspected ( 5.2 ). Hypoglycemia: Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing the dose of insulin secretagogue or insulin may be necessary ( 5.3 ).
Hypersensitivity
Reactions: Serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) have occurred. Discontinue TRULICITY and promptly seek medical advice ( 5.4 ).
Acute Kidney Injury
Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion ( 5.5 ).
Severe Gastrointestinal Adverse
Reactions: Use may be associated with gastrointestinal adverse reactions, sometimes severe. TRULICITY is not recommended in patients with severe gastroparesis ( 5.6 ).
Diabetic Retinopathy
Complications: Have been reported in a cardiovascular outcomes trial. Monitor patients with a history of diabetic retinopathy ( 5.7 ).
Acute Gallbladder
Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated ( 5.8 ).
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 ( 5.9 ).
5.1 Risk of Thyroid C-cell Tumors In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . Glucagon-like peptide-1 (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. It is unknown whether TRULICITY will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. One case of MTC was reported in a patient treated with TRULICITY in a clinical trial. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). 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. TRULICITY 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 TRULICITY 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 TRULICITY. 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, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including TRULICITY <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . After initiation of TRULICITY, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue TRULICITY and initiate appropriate management.
5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving TRULICITY 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 ) and 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.
5.4 Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions including anaphylactic reactions and angioedema in patients treated with TRULICITY <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . If a hypersensitivity reaction occurs, discontinue TRULICITY; treat promptly per standard of care, and monitor until signs and symptoms resolve. TRULICITY is contraindicated in patients with a previous serious hypersensitivity reaction to dulaglutide or to any of the components of TRULICITY. 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 TRULICITY.
5.5 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 GLP-1 receptor agonists, including TRULICITY <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . 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 TRULICITY that could lead to volume depletion, especially during dosage initiation and escalation of TRULICITY.
5.6 Severe Gastrointestinal Adverse Reactions Use of TRULICITY has been associated with gastrointestinal adverse reactions, sometimes severe <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> . In the pool of placebo-controlled trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving TRULICITY (0.75 mg 2.2%, 1.5 mg 4.3%) than placebo (1.4%). TRULICITY is not recommended in patients with severe gastroparesis.
5.7 Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy In a cardiovascular outcomes trial with a median follow up of 5.4 years involving patients with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors, diabetic retinopathy complications occurred in patients treated with TRULICITY 1.5 mg (1.9%) and placebo (1.5%). These events were prospectively ascertained as a secondary composite endpoint. The proportion of patients with diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (TRULICITY 8.5%, placebo 6.2%) than among patients without a known history of diabetic retinopathy (TRULICITY 1%, placebo 1%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
5.8 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 a cardiovascular outcomes trial with a median follow up of 5.4 years, cholelithiasis occurred at a rate of 0.62/100 patient-years in TRULICITY-treated patients and 0.56/100 patient-years in placebo-treated patients after adjusting for prior cholecystectomy. Serious events of acute cholecystitis were reported in 0.5% and 0.3% of patients on TRULICITY and placebo respectively. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation TRULICITY 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 TRULICITY, including whether modifying preoperative fasting recommendations or temporarily discontinuing TRULICITY 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 TRULICITY.