What the FDA changed in 2020

Approved uses

Removed in this revision

• -Removed: Saxenda should not be used in combination with any other GLP-1 receptor agonist. • The safety and effectiveness of Saxenda in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

1 entry reworded without a change of meaning.

Dosage and administration

This section was substantially rewritten in this revision: 13 entries added, 17 removed. A change this large is usually a reorganization of the document rather than a set of individual edits, so the wording is not quoted line by line.

3 entries reworded without a change of meaning.

Forms and strengths

Added in this revision

• +Added: Injection: 6 mg/mL clear, colorless solution in a 3 mL pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg.

Removed in this revision

• -Removed: Solution for subcutaneous injection, pre-filled, multi-dose, pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg (6 mg/mL, 3 mL).

Contraindications

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: In a SAXENDA pediatric clinical trial, pancreatitis was not independently adjudicated.
• +Added: Pancreatitis was reported in 1 (0.8%) SAXENDA-treated patient and resulted in treatment discontinuation.
• +Added: Hypoglycemia Adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia with use of SAXENDA, including severe hypoglycemia.
• +Added: The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.
• +Added: Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
• +Added: In the pediatric clinical trial, patients did not have type 2 diabetes but were provided with blood glucose meters.
• +Added: Clinically significant hypoglycemia, defined as blood glucose <54 mg/dL, occurred in 1.6% of the SAXENDA- treated patients compared to 0.8% of placebo-treated patients.
• +Added: Inform all pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
• +Added: In a pediatric clinical trial, mean increases from baseline in resting heart rate of 3 to 7 bpm were observed with SAXENDA treatment.
• +Added: In a SAXENDA pediatric clinical trial, 1 (0.8%) of the 125 SAXENDA-treated patients died by suicide.
• +Added: There was insufficient information to establish a causal relationship to SAXENDA.

Removed in this revision

• -Removed: Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy The risk for hypoglycemia is increased when Saxenda is used in combination with insulin secretagogues (for example, sulfonylureas) or insulin in patients with type 2 diabetes mellitus.
• -Removed: Therefore, patients may require a lower dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin in this setting.
• -Removed: Saxenda can lower blood glucose.
• -Removed: If needed, adjust co-administered anti-diabetic drugs based on glucose monitoring results and risk of hypoglycemia.

6 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: All patients received study drug in addition to a reduced-calorie diet and increased physical activity counseling.
• +Added: Adverse reactions reported in greater than or equal to 3% of SAXENDA-treated pediatric patients and more frequently than in placebo-treated patients are shown in Table 5.
• +Added: Adverse Reactions Occurring in > 2% of SAXENDA-treated Adult Patients and More Frequently than Placebo 1 The most common reactions, each reported by 1% to 2.5% of SAXENDA-treated patients and more commonly than by placebo-treated patients, included erythema, pruritus, and rash at the injection site. 2 Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia in patients with type 2 diabetes not on concomitant insulin (Study 2, Saxenda N=423, Placebo N=212).
• +Added: T2DM = type 2 diabetes mellitus Table 5.
• +Added: Adverse Reactions Occurring in > 3% of SAXENDA-treated Pediatric Patients and More Frequently than Placebo in a 56 Week Clinical Trial 1 Defined as blood glucose <70 mg/dL with symptoms of hypoglycemia.
• +Added: Pediatric patients did not have type 2 diabetes mellitus.
• +Added: See text below for more detailed hypoglycemia information.
• +Added: Pediatric Patients without Type 2 Diabetes In a 56-week placebo-controlled clinical trial of pediatric patients without type 2 diabetes mellitus in which blood glucose meters were provided, 19 (15.2%) of SAXENDA-treated patients had hypoglycemia with a blood glucose less than 70 mg/dL with symptoms as compared to 5 (4.0%) of placebo-treated patients.
• +Added: Four events of hypoglycemia defined as a plasma glucose less than 54 mg/dL occurred in 2 (1.6%) of 125 SAXENDA-treated patients and 1 event occurred in 1 (0.8%) of 126 placebo-treated patients.
• +Added: No severe hypoglycemic episodes, defined as requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, occurred in the SAXENDA treatment group.
• +Added: In a pediatric clinical trial, 8.0% of patients treated with SAXENDA versus no patients who received placebo discontinued treatment as a result of gastrointestinal adverse reactions.
• +Added: Most adverse reactions leading to discontinuation were due to vomiting and nausea (4.8% and 3.2% of SAXENDA-treated patients, respectively).
• +Added: In a pediatric clinical trial, anti-liraglutide antibodies were detected in 14 (12%) of 117 SAXENDA-treated patients with a post-baseline assessment; 5 (4.3%) had persistent antibodies as defined by more than 2 antibody visits at least 16 weeks apart.
• +Added: Two patients (1.7%) remained positive throughout the follow-up period; 1 (0.9%) had antibodies cross reactive to native GLP-1.
• +Added: No patients had neutralizing antibodies.

Removed in this revision

• -Removed: All patients received study drug in addition to diet and exercise counseling.
• -Removed: Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients and More Frequently than with Placebo* 1 Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia in patients with type 2 diabetes not on concomitant insulin (Study 2).
• -Removed: The frequency of hypoglycemia may be higher if the dose of sulfonylurea is not reduced.
• -Removed: Injection Site Reactions Injection site reactions were reported in approximately 13.9% of Saxenda-treated patients and 10.5% of placebo-treated patients.
• -Removed: The most common reactions, each reported by 1% to 2.5% of Saxenda-treated patients and more commonly than by placebo-treated patients, included erythema, pruritus, and rash at the injection site. 0.6% of Saxenda-treated patients and 0.5% of placebo-treated patients discontinued treatment due to injection site reactions.

19 entries reworded without a change of meaning.

Contraindications

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Acute Tubulointerstitial Nephritis Acute tubulointerstial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy.
• +Added: Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia).
• +Added: In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).
• +Added: Discontinue PREVACID or PREVACID SoluTab and evaluate patients with suspected acute TIN.

Removed in this revision

• -Removed: Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including PREVACID and PREVACID SoluTab.
• -Removed: Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.
• -Removed: Discontinue PREVACID or PREVACID SoluTab if acute interstitial nephritis develops.

Adverse reactions

1 entry reworded without a change of meaning.

Contraindications

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy.
• +Added: Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia).
• +Added: In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).
• +Added: Discontinue PROTONIX and evaluate patients with suspected acute TIN.

Removed in this revision

• -Removed: Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including PROTONIX.
• -Removed: Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.
• -Removed: Discontinue PROTONIX if acute interstitial nephritis develops.

Adverse reactions

1 entry reworded without a change of meaning.

Contraindications

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy.
• +Added: Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia).
• +Added: In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).
• +Added: Discontinue NEXIUM and evaluate patients with suspected acute TIN.

Removed in this revision

• -Removed: Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including NEXIUM.
• -Removed: Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.
• -Removed: Discontinue NEXIUM if acute interstitial nephritis develops.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: Limitations of Use: VICTOZA should not be used in patients with type 1 diabetes mellitus.
• +Added: VICTOZA contains liraglutide and should not be coadministered with other liraglutide-containing products.

Removed in this revision

• -Removed: Limitations of Use: • VICTOZA should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. • The concurrent use of VICTOZA and prandial insulin has not been studied.

Contraindications

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Inform patients using these concomitant medications and pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

2 entries reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: General Dosing and Administration Pregnancy testing is recommended before initiating Qsymia in patients who can become pregnant and monthly during Qsymia therapy and weight [pounds (lb) or kilograms (kg)] is provided below.

Removed in this revision

• -Removed: General Dosing and Administration Determine the patient's BMI.
• -Removed: BMI is calculated by dividing weight (in kilograms) by height (in meters) squared.
• -Removed: A BMI conversion chart (Table 1) based on height [inches (in) or centimeters (cm)] and weight [pounds (lb) or kilograms (kg)] is provided below.

Warnings and precautions

Added in this revision

• +Added: Pregnancy testing is recommended before initiating Qsymia treatment in patients who can become pregnant and monthly during Qsymia therapy.
• +Added: Advise patients who can become pregnant of the potential risk to a fetus and to use effective contraception during Qsymia therapy.

Removed in this revision

• -Removed: If Qsymia is used during pregnancy or if a patient becomes pregnant while taking Qsymia, treatment should be discontinued immediately, and the patient should be apprised of the potential hazard to a fetus.
• -Removed: Females of reproductive potential should have a negative pregnancy test before starting Qsymia and monthly thereafter during Qsymia therapy.
• -Removed: Females of reproductive potential should use effective contraception during Qsymia therapy.

2 entries reworded without a change of meaning.

Drug interactions

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Risk of Heart Valve Thickening in Pediatric Patients Less Than One Year of Age PREVACID and PREVACID SoluTab are not approved in pediatric patients less than one year of age.
• +Added: Nonclinical studies in juvenile rats with lansoprazole have demonstrated an adverse effect of heart valve thickening.
• +Added: The risk of heart valve injury does not appear to be relevant to patients one year of age and older.

1 entry reworded without a change of meaning.

Adverse reactions

Removed in this revision

• -Removed: Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment.
• -Removed: In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials.
• -Removed: The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients in Table 1.
• -Removed: Headache was also seen at greater than 1% incidence but was more common on placebo.
• -Removed: The incidence of diarrhea was similar between patients who received placebo and patients who received 15 and 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9, 1.4, 4.2, and 7.4%, respectively).
• -Removed: The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.
• -Removed: In the risk reduction study of PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with PREVACID, misoprostol, and placebo was 5, 22, and 3%, respectively.
• -Removed: Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study.
• -Removed: Additional reactions from this study not previously observed in other clinical trials with PREVACID included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment.
• -Removed: Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below: Body as a Whole - abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain Cardiovascular System - angina, arrhythmia, bradycardia, cerebrovascular...
• -Removed: The majority of these cases are foreign-sourced and a relationship to PREVACID or PREVACID SoluTab has not been established.
• -Removed: Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
• -Removed: These events are listed below by COSTART body system.
• -Removed: Body as a Whole - anaphylactic/anaphylactoid reactions, systemic lupus erythematosus;
• -Removed: Digestive System - hepatotoxicity, pancreatitis, vomiting;
• -Removed: Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura;
• -Removed: Infections and Infestations - Clostridium difficile- associated diarrhea;
• -Removed: Metabolism and Nutritional Disorders - hypomagnesemia;
• -Removed: Musculoskeletal System - bone fracture, myositis;
• -Removed: Skin and Appendages - severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), cutaneous lupus erythematosus;
• -Removed: Special Senses - speech disorder;
• -Removed: Urogenital System - interstitial nephritis, urinary retention.
• -Removed: Combination Therapy with Amoxicillin and Clarithromycin In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed.
• -Removed: Adverse reactions that have occurred have been limited to those that had been previously reported with PREVACID, amoxicillin, or clarithromycin.
• -Removed: Triple Therapy: PREVACID/amoxicillin/clarithromycin The most frequently reported adverse reactions for patients who received triple therapy for 14 days were diarrhea (7%), headache (6%), and taste perversion (5%).
• -Removed: There were no statistically significant differences in the frequency of reported adverse reactions between the 10 and 14 day triple therapy regimens.
• -Removed: No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen.
• -Removed: Dual Therapy: PREVACID/amoxicillin The most frequently reported adverse reactions for patients who received PREVACID three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%).
• -Removed: No treatment-emergent adverse reactions were observed at significantly higher rates with PREVACID three times daily plus amoxicillin three times daily dual therapy than with PREVACID alone.
• -Removed: For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information.
• -Removed: Laboratory Values The following changes in laboratory parameters in patients who received PREVACID were reported as adverse reactions: Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased,...
• -Removed: Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported.
• -Removed: Additional isolated laboratory abnormalities were reported.
• -Removed: In the placebo-controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and PREVACID, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit.
• -Removed: None of these patients who received PREVACID reported jaundice at any time during the study.
• -Removed: In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.
• -Removed: For information about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information.

1 entry reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: TRULICITY is not a substitute for insulin.
• -Removed: The use of TRULICITY is not recommended in patients with pre-existing severe gastrointestinal disease.

2 entries reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: If additional glycemic control is needed, increase the dose to 3 mg once weekly after at least 4 weeks on the 1.5 mg dose.
• +Added: If additional glycemic control is needed, increase the dose to the maximum dose of 4.5 mg once weekly after at least 4 weeks on the 3 mg dose.
• +Added: Rotate injection sites with each dose.
• +Added: Inspect TRULICITY visually before use.
• +Added: It should appear clear and colorless.
• +Added: Do not use TRULICITY if particulate matter or coloration is seen.
• +Added: When using TRULICITY with insulin, administer as separate injections and never mix.

Removed in this revision

• -Removed: The maximum recommended dose is 1.5 mg once weekly.
• -Removed: Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin When initiating TRULICITY, consider reducing the dosage of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of hypoglycemia.
• -Removed: Important Administration Instructions Prior to initiation of TRULICITY, patients should be trained by their healthcare professional on proper injection technique.
• -Removed: Training reduces the risk of administration errors such as improper injection site, needle sticks, and incomplete dosing.
• -Removed: Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.
• -Removed: The instructions can also be found at www.trulicity.com.
• -Removed: When using TRULICITY with insulin, instruct patients to administer as separate injections and to never mix the products.
• -Removed: When injecting in the same body region, advise patients to use a different injection site each week.
• -Removed: TRULICITY must not be administered intravenously or intramuscularly.
• -Removed: TRULICITY solution should be visually inspected for particulate matter and discoloration prior to administration.

4 entries reworded without a change of meaning.

Forms and strengths

Added in this revision

• +Added: Injection: TRULICITY is a clear and colorless solution available as: 0.75 mg/0.5 mL solution in a single-dose pen 1.5 mg/0.5 mL solution in a single-dose pen 3 mg/0.5 mL solution in a single-dose pen 4.5 mg/0.5 mL solution in a single-dose pen

Removed in this revision

• -Removed: Injection: 0.75 mg/0.5 mL solution in a single-dose pen Injection: 1.5 mg/0.5 mL solution in a single-dose pen

Contraindications

Added in this revision

• +Added: Prior serious hypersensitivity reaction to dulaglutide or to any of the product components.

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Based on an analysis of adjudicated events in a clinical study evaluating Trulicity 1.5 mg, 3 mg, or 4.5 mg once weekly, pancreatitis occurred in 1 patient exposed to TRULICITY 1.5 mg (0.2%), in 2 patients exposed to TRULICITY 3 mg (0.3%), and 3 patients exposed to TRULICITY 4.5 mg (0.5%).

3 entries reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: The delay in gastric emptying is dose-dependent but is attenuated with the recommended dose escalation to higher doses of TRULICITY.
• +Added: The delay is largest after the first dose and diminishes with subsequent doses.
• +Added: There is limited experience with the use of concomitant medications in clinical trials with TRULICITY doses of 3 mg and 4.5 mg.
• +Added: 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.

Removed in this revision

• -Removed: Caution should be exercised when oral medications are concomitantly administered with TRULICITY.

3 entries reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Dose Adjustment in Patients with Hepatic Impairment In patients with moderate hepatic impairment, the maximum recommended daily maintenance dose of CONTRAVE is two tablets (one tablet each morning and evening).
• +Added: CONTRAVE is not recommended for use in patients with severe hepatic impairment.

Removed in this revision

• -Removed: No dose adjustment is required in patients with mild renal impairment.
• -Removed: Dose Adjustment in Patients with Hepatic Impairment In patients with hepatic impairment, the maximum recommended daily dose of CONTRAVE is one tablet in the morning.

Forms and strengths

1 entry reworded without a change of meaning.

Contraindications

1 entry reworded without a change of meaning.

Adverse reactions

2 entries reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: Saxenda should not be used in combination with any other GLP-1 receptor agonist. • Saxenda has not been studied in patients taking insulin.

2 entries reworded without a change of meaning.

Dosage and administration

Removed in this revision

• -Removed: Saxenda and insulin should not be used together.

1 entry reworded without a change of meaning.

Warnings and precautions

Removed in this revision

• -Removed: Saxenda should not be used in patients taking insulin.

4 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients and More Frequently than with Placebo* 1 Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia in patients with type 2 diabetes not on concomitant insulin (Study 2).
• +Added: In this trial, among patients taking a sulfonylurea, hypoglycemia defined as a plasma glucose less than 54 mg/dL with or without symptoms occurred in 31 (28.2%) of 110 Saxenda-treated patients and 7 (12.7%) of 55 placebo-treated patients.
• +Added: Among patients not taking a sulfonylurea, blood glucose less than 54 mg/dL with or without symptoms occurred in 22 (7.1%) of 312 Saxenda-treated patients and 7 (4.5%) of 157 placebo-treated patients.
• +Added: In a Saxenda clinical trial in patients with overweight (excess weight) or obesity with type 2 diabetes mellitus treated with basal insulin and Saxenda in combination with a reduced-calorie diet and increased physical activity and up to 2 oral anti-diabetes medications, severe hypoglycemia was reported by 3 (1.5%) of 195 Saxenda-treated patients and 2 (1.0%) of 197 placebo-treated patients.
• +Added: No meaningful difference in hypoglycemia, defined as blood glucose less than 54 mg/dL with or without symptoms, was reported between groups.

Removed in this revision

• -Removed: Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients and More Frequently than with Placebo* 1 Documented symptomatic (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) in patients with type 2 diabetes (Study 2).
• -Removed: T2DM = type 2 diabetes mellitus * Adverse reactions for trials with treatment period up to 56 weeks Hypoglycemia Saxenda can lower blood glucose.
• -Removed: Each of these 3 Saxenda-treated patients was also taking a sulfonylurea.
• -Removed: In the same trial, among patients taking a sulfonylurea, documented symptomatic hypoglycemia (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) occurred in 48 (43.6%) of 110 Saxenda-treated patients and 15 (27.3%) of 55 placebo-treated patients.
• -Removed: Among patients not taking a sulfonylurea, documented symptomatic hypoglycemia occurred in 49 (15.7%) of 312 Saxenda-treated patients and 12 (7.6%) of 157 placebo-treated patients.

6 entries reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: TRULICITY ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.

Removed in this revision

• -Removed: TRULICITY ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• -Removed: Limitations of Use TRULICITY is not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans.
• -Removed: Prescribe TRULICITY only to patients for whom the potential benefits outweigh the potential risk.

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND).
• +Added: 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%).
• +Added: These events were prospectively ascertained as a secondary composite endpoint.
• +Added: 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 1.0%, placebo 1.0%).
• +Added: Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy.
• +Added: Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.

Removed in this revision

• -Removed: Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRULICITY.

1 entry reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Adverse reactions

Removed in this revision

• -Removed: Pool of Placebo-controlled Trials The data in Table 1 are derived from placebo-controlled trials.
• -Removed: These data reflect exposure of 1670 patients to TRULICITY and a mean duration of exposure to TRULICITY of 23.8 weeks.
• -Removed: Across the treatment arms, the mean age of patients was 56 years, 1% were 75 years or older and 53% were male.
• -Removed: The population in these studies was 69% White, 7% Black or African American, 13% Asian; 30% were of Hispanic or Latino ethnicity.
• -Removed: At baseline, the population had diabetes for an average of 8.0 years and had a mean HbA1c of 8.0%.
• -Removed: At baseline, 2.5% of the population reported retinopathy.
• -Removed: Baseline estimated renal function was normal or mildly impaired (eGFR ≥60 mL/min/1.73 m 2) in 96.0% of the pooled study populations.
• -Removed: Table 1 shows common adverse reactions, excluding hypoglycemia, associated with the use of TRULICITY in a pool of placebo-controlled trials.
• -Removed: These adverse reactions were not present at baseline, occurred more commonly on TRULICITY than on placebo, and occurred in at least 5% of patients treated with TRULICITY.
• -Removed: Gastrointestinal Adverse Reactions In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving TRULICITY than placebo (placebo 21.3%, 0.75 mg 31.6%, 1.5 mg 41.0%).
• -Removed: More patients receiving TRULICITY 0.75 mg (1.3%) and TRULICITY 1.5 mg (3.5%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.2%).
• -Removed: Investigators graded the severity of gastrointestinal adverse reactions occurring on 0.75 mg and 1.5 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.
• -Removed: In addition to the reactions in Table 1, the following adverse reactions were reported more frequently in TRULICITY-treated patients than placebo (frequencies listed, respectively, as: placebo; 0.75 mg; 1.5 mg): constipation (0.7%, 3.9%, 3.7%), flatulence (1.4%, 1.4%, 3.4%), abdominal distension (0.7%, 2.9%, 2.3%), gastroesophageal reflux disease (0.5%, 1.7%, 2.0%), and eructation (0.2%, 0.6%, 1.6%).
• -Removed: Pool of Placebo- and Active-Controlled Trials The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 6 placebo- and active-controlled trials evaluating the use of TRULICITY as monotherapy and add-on therapy to oral medications or insulin.
• -Removed: In this pool, a total of 3342 patients with type 2 diabetes were treated with TRULICITY for a mean duration of 52 weeks.
• -Removed: The mean age of patients was 56 years, 2% were 75 years or older and 51% were male.
• -Removed: The population in these studies was 71% White, 7% Black or African American, 11% Asian; 32% were of Hispanic or Latino ethnicity.
• -Removed: At baseline, the population had diabetes for an average of 8.2 years and had a mean HbA1c of 7.6-8.5%.
• -Removed: At baseline, 5.2% of the population reported retinopathy.
• -Removed: Baseline estimated renal function was normal or mildly impaired (eGFR ≥60 mL/min/1.73 m 2) in 95.7% of the TRULICITY population.
• -Removed: In the pool of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.
• -Removed: Other Adverse Reactions Hypoglycemia Table 2 summarizes the incidence of hypoglycemia in the placebo-controlled clinical studies: 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.
• -Removed: Hypoglycemia was more frequent when TRULICITY was used in combination with a sulfonylurea or insulin than when used with non-secretagogues.
• -Removed: In a 78-week clinical trial, hypoglycemia (glucose level <54 mg/dL) occurred in 20% and 21% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with a sulfonylurea.
• -Removed: Severe hypoglycemia occurred in 0% and 0.7% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with a sulfonylurea.
• -Removed: In a 52-week clinical trial, hypoglycemia (glucose level <54 mg/dL) occurred in 77% and 69% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with prandial insulin.
• -Removed: Severe hypoglycemia occurred in 2.7% and 3.4% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, were co-administered with prandial insulin.
• -Removed: Refer to Table 2 for the incidence of hypoglycemia in patients treated in combination with basal insulin glargine.
• -Removed: Heart Rate Increase and Tachycardia-Related Adverse Reactions TRULICITY 0.75 mg and 1.5 mg resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm).
• -Removed: The long-term clinical effects of the increase in HR have not been established.
• -Removed: Adverse reactions of sinus tachycardia were reported more frequently in patients exposed to TRULICITY.
• -Removed: Sinus tachycardia was reported in 3.0%, 2.8%, and 5.6% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.
• -Removed: Persistence of sinus tachycardia (reported at more than 2 visits) was reported in 0.2%, 0.4% and 1.6% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.
• -Removed: Episodes of sinus tachycardia, associated with a concomitant increase from baseline in heart rate of ≥15 beats per minute, were reported in 0.7%, 1.3% and 2.2% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.
• -Removed: Hypersensitivity Systemic hypersensitivity adverse reactions, sometimes severe (e.g., severe urticaria, systemic rash, facial edema, lip swelling), occurred in 0.5% of patients on TRULICITY in the four Phase 2 and five Phase 3 studies.
• -Removed: Injection-site Reactions In the placebo-controlled studies, injection-site reactions (e.g., injection-site rash, erythema) were reported in 0.5% of TRULICITY-treated patients and in 0.0% of placebo-treated patients.
• -Removed: PR Interval Prolongation and Adverse Reactions of First-Degree Atrioventricular (AV) Block A mean increase from baseline in PR interval of 2-3 milliseconds was observed in TRULICITY-treated patients in contrast to a mean decrease of 0.9 milliseconds in placebo-treated patients.
• -Removed: The adverse reaction of first-degree AV block occurred more frequently in patients treated with TRULICITY than placebo (0.9%, 1.7% and 2.3% for placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively).
• -Removed: On electrocardiograms, a PR interval increase to at least 220 milliseconds was observed in 0.7%, 2.5% and 3.2% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.
• -Removed: Amylase and Lipase Increase 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%.

1 entry reworded without a change of meaning.