TRULICITY

75 mg injected subcutaneously once weekly. 5 mg once weekly for additional glycemic control. 5 mg increments after at least 4 weeks on the current dosage. 5 mg injected subcutaneously once weekly. 75 mg injected subcutaneously once weekly.

75 mg dosage. 3 ) If a dose is missed, administer the missed dose as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. 4 ) Administer once weekly at any time of day with or without food. Inject subcutaneously in the abdomen, thigh, or upper arm.

75 mg injected subcutaneously once weekly. 5 mg once weekly for additional glycemic control. 5 mg increments after at least 4 weeks on the current dosage. 5 mg injected subcutaneously once weekly. 75 mg injected subcutaneously once weekly.

75 mg dosage. 3 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to administer the dose as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day.

In each case, patients can then resume their regular once weekly dosing schedule. The day of weekly administration can be changed, if necessary, as long as the last dose was administered 3 or more days before the new day of administration.

4 Important Administration Instructions Prior to initiation, train patients and caregivers on proper injection technique [see Instructions for Use] . Administer TRULICITY once weekly, any time of day, with or without food. Inject TRULICITY subcutaneously in the abdomen, thigh, or upper arm.

Rotate injection sites with each dose. Inspect TRULICITY visually before use. It should appear clear and colorless. Do not use TRULICITY if particulate matter or coloration is seen. When using TRULICITY with insulin, administer as separate injections and never mix.

It is acceptable to inject TRULICITY and insulin in the same body region, but the injections should not be adjacent to each other.

1 ). gov/medwatch . 1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

8 weeks [see Clinical Studies ( 14 )] . The mean age of patients was 56 years, 1% were 75 years or older and 53% were male. The population was 69% White, 7% Black or African American, 13% Asian; 30% were of Hispanic or Latino ethnicity.

5% of the population reported retinopathy. 73 m 2 ) in 96%. Table 1 shows adverse reactions, excluding hypoglycemia, occurring in ≥5% of TRULICITY treated adult patients and more commonly than placebo in a pool of placebo-controlled trials.

Table 1:

Adverse Reactions in Pool of Placebo-Controlled Trials That Occurred in ≥5% of TRULICITY-Treated Adult Patients with Type 2 Diabetes Mellitus a Includes diarrhea, fecal volume increased, frequent bowel movements. b Includes retching, vomiting, vomiting projectile.

c Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, gastrointestinal pain. d Includes fatigue, asthenia, malaise.

Note:

Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction. 5 mg 41%). 2%). 5 mg of TRULICITY as “mild” in 58% and 48% of cases, respectively, “moderate” in 35% and 42% of cases, respectively, or “severe” in 7% and 11% of cases, respectively.

6%). 3 )] . The adverse reaction profile is consistent with previous clinical trials in adults.

Table 2:

Adverse Reactions That Occurred in ≥5% of TRULICITY-treated Adult Patients with Type 2 Diabetes Mellitus in a Clinical Trial through 36 Weeks a a Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction.

6 Other Adverse Reactions in Adults Hypoglycemia Table 3 summarizes the incidence of hypoglycemia in the placebo-controlled clinical studies in adult patients with type 2 diabetes mellitus: episodes with a glucose level <54 mg/dL with or without symptoms, and severe hypoglycemia, defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

7 0 Hypoglycemia was more frequent when TRULICITY was used in combination with a sulfonylurea or insulin than when used with non-secretagogues. 5 mg, respectively, were co-administered with a sulfonylurea. 5 mg, respectively, were co-administered with a sulfonylurea.

5 mg, respectively, were co-administered with prandial insulin. 5 mg, respectively, were co-administered with prandial insulin. Refer to Table 3 for the incidence of hypoglycemia in patients treated in combination with basal insulin glargine.

2%, respectively. 56/100 patient-years in placebo-treated patients after adjusting for prior cholecystectomy. 3% of patients on TRULICITY and placebo respectively. 5 mg resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm).

Adverse reactions of sinus tachycardia were reported more frequently in patients exposed to TRULICITY. 5 mg, respectively. 5 mg, respectively. 5 mg, respectively. 5% of adult patients on TRULICITY in clinical studies. 0% of placebo-treated patients.

9 milliseconds in placebo-treated patients. 5 mg, respectively). 5 mg, respectively. Amylase and Lipase Increase Adult patients exposed to TRULICITY had mean increases from baseline in lipase and/or pancreatic amylase of 14% to 20%, while placebo-treated patients had mean increases of up to 3%.

6 ) ]. 5 years and 71% of patients were female. Overall, 55% were White, 15% were Black or African American, 12% were Asian, 10% were American Indian or Alaska Native, 5% were other races, and 3% had unknown race. Additionally, 55% were Hispanic or Latino, 42% were not Hispanic or Latino, and 3% had unknown ethnicity.

1 kg/m 2 . 5 mg subcutaneously once-weekly was consistent with that described above for adult patients with type 2 diabetes mellitus with the exception of injection site reactions. 0% (1 patient) in the placebo group. 2 Postmarketing Experience The following additional adverse reactions have been reported during post-approval use of TRULICITY.

Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: ileus Hepatobiliary: cholecystitis, cholelithiasis requiring cholecystectomy, cholestasis, elevation of liver enzymes, hepatitis Hypersensitivity: anaphylactic reactions, angioedema Renal: acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis

1 ).

Pancreatitis:

Has been reported in clinical trials. Discontinue promptly if pancreatitis is suspected. 2 ).

Hypoglycemia:

Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. 3 ). , anaphylactic reactions and angioedema) have occurred. 4 ). 5 ).

Severe Gastrointestinal Disease:

Use may be associated with gastrointestinal adverse reactions, sometimes severe. 6 ).

Diabetic Retinopathy Complications:

Have been reported in a cardiovascular outcomes trial. 7 ). 8 ). 1 )] . 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. 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. 7 cases per 1000 patient years).

88 cases per 1000 patient years). 5%). 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, promptly discontinue TRULICITY and initiate appropriate management. If pancreatitis is confirmed, TRULICITY should not be restarted. TRULICITY has not been evaluated in patients with a prior history of pancreatitis.

Consider other antidiabetic therapies in patients with a history of pancreatitis. 1 ) and Drug Interactions ( 7 )]. 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. 2 )] . 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 Acute Kidney Injury In patients treated with GLP-1 receptor agonists, including TRULICITY, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis.

Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Because these reactions may worsen renal function, use caution when initiating or escalating doses of TRULICITY in patients with renal impairment.

6 )] . 1 )] . TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients. 5%). These events were prospectively ascertained as a secondary composite endpoint.

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.

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. 56/100 patient-years in placebo-treated patients after adjusting for prior cholecystectomy.

3% of patients on TRULICITY and placebo respectively. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

1 )] . Serious hypersensitivity reaction to dulaglutide or to any of the product components. 4 )] . 1 ). 4 ).