What the FDA changed in 2025

Approved uses

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: A patient may self-inject if a healthcare provider determines that it is appropriate.

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

3 entries reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: Mitotane Avoid concomitant use of ALDACTONE and mitotane.
• +Added: Spironolactone reduces mitotane plasma levels.

Approved uses

Added in this revision

• +Added: RYBELSUS 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 (CV) events (CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events.

Removed in this revision

• -Removed: RYBELSUS is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• -Removed: Limitations of Use RYBELSUS is not indicated for use in patients with type 1 diabetes mellitus.

Dosage and administration

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: 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 semaglutide.
• +Added: The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea.
• +Added: Monitor renal function in patients reporting adverse reactions to RYBELSUS that could lead to volume depletion, especially during dosage initiation and escalation of RYBELSUS.
• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.
• +Added: In a 4-year CV outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with RYBELSUS 14 mg and in 0.9% of placebo-treated patients.
• +Added: In Trial 7, cholecystitis was reported in 1.1% of patients treated with RYBELSUS 14 mg and in 0.7% of placebo-treated patients.

Removed in this revision

• -Removed: Acute Kidney Injury There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists, including semaglutide.
• -Removed: Some of these events have been reported in patients without known underlying renal disease.
• -Removed: A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea or dehydration.
• -Removed: Monitor renal function when initiating or escalating doses of RYBELSUS in patients reporting severe adverse gastrointestinal reactions.
• -Removed: Cholelithiasis was not reported in RYBELSUS 14 mg or placebo-treated patients.

3 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: In a 4-year CV outcomes trial (Trial 7), 4,825 patients were randomized to RYBELSUS for a median follow-up of 49.6 months and 4,825 patients were randomized to placebo for a median follow-up of 49.4 months.
• +Added: Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest.
• +Added: Study drug was permanently discontinued due to an adverse event in 15.5% of RYBELSUS-treated patients and 11.6% of placebo-treated patients.
• +Added: Additional information from this trial is included in subsequent sections below, when relevant.
• +Added: In a 4-year CV outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with RYBELSUS 14 mg and in 0.9% of placebo-treated patients.
• +Added: In Trial 7, cholecystitis was reported in 1.1% of patients treated with RYBELSUS 14 mg and in 0.7% of placebo-treated patients.
• +Added: Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Gastrointestinal: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction • Hypersensitivity: anaphylaxis, angioedema, rash, urticaria • Hepatobiliary: cholecystitis, cholelithiasis requiring...

Removed in this revision

• -Removed: Cholelithiasis was not reported in RYBELSUS 14 mg or placebo-treated patients.
• -Removed: Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Gastrointestinal: ileus • Hypersensitivity: anaphylaxis, angioedema, rash, urticaria • Hepatobiliary: cholecystitis, cholelithiasis requiring cholecystectomy • Nervous system disorders: dizziness, dysesthesia, dysgeusia • Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1...

5 entries reworded without a change of meaning.

Drug interactions

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Inject ZEPBOUND subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm.

Removed in this revision

• -Removed: Inject ZEPBOUND subcutaneously in the abdomen, thigh, or upper arm.

Warnings and precautions

Added in this revision

• +Added: ZEPBOUND is not recommended in patients with severe gastroparesis.
• +Added: 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, or ZEPBOUND.
• +Added: The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea.

Removed in this revision

• -Removed: ZEPBOUND has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.
• -Removed: Acute Kidney Injury Use of ZEPBOUND has been associated with acute kidney injury, which can result from dehydration due to gastrointestinal adverse reactions to ZEPBOUND, including nausea, vomiting, and diarrhea.
• -Removed: In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis.
• -Removed: Some of these events have been reported in patients without known underlying renal disease.
• -Removed: A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.
• -Removed: In clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure).
• -Removed: In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), 0.2% of ZEPBOUND-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure).
• -Removed: The exposure-adjusted incidence rate for treatment-emergent adjudication-confirmed pancreatitis in the pooled clinical studies for OSA (Studies 5 and 6) was 0.84 patients per 100 years for ZEPBOUND and 0 for placebo-treated patients.
• -Removed: Continuation of ZEPBOUND after a confirmed diagnosis of pancreatitis should be individually determined in the clinical judgment of a patient's health care provider.

3 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: Inject MOUNJARO subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm.

Removed in this revision

• -Removed: Inject MOUNJARO subcutaneously in the abdomen, thigh, or upper arm.

Dosage and administration

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

1 entry reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Cardiovascular Safety Cardiovascular safety was assessed (LEADER, NCT01179048) in 9,340 patients with inadequately controlled type 2 diabetes and cardiovascular disease randomized to liraglutide 1.8 mg or placebo in addition to standard of care treatments for type 2 diabetes for a median duration of 3.5 years.
• +Added: The primary endpoint was the time from randomization to first occurrence of a major adverse cardiovascular event (MACE) defined as: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.
• +Added: No increased risk for MACE was observed with liraglutide 1.8 mg.
• +Added: The total number of primary component MACE endpoints was 1,302 [608 (13.0%) with liraglutide 1.8 mg and 694 (14.9%) with placebo].
• +Added: Liraglutide 1.8 mg (Victoza) is used in the treatment of type 2 diabetes mellitus in adults.
• +Added: The efficacy of liraglutide at doses below 3 mg daily has not been established for weight reduction.

4 entries reworded without a change of meaning.

Forms and strengths

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

3 entries reworded without a change of meaning.

Adverse reactions

10 entries reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: CONTRAVE 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 overweight in the presence of at least one weight-related comorbid condition.
• +Added: CONTRAVE contains naltrexone and bupropion.
• +Added: Coadministration with other naltrexone-containing products is not recommended.
• +Added: Coadministration with other bupropion-containing products is contraindicated.

Removed in this revision

• -Removed: CONTRAVE is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m 2 or greater (obese) or 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).
• -Removed: The safety and effectiveness of CONTRAVE in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

Dosage and administration

Added in this revision

• +Added: Recommended Dosage Initiate and escalate the dosage of CONTRAVE according to the schedule in Table 1: A total daily dosage of 32 mg of naltrexone hydrochloride (HCl) and 360 mg bupropion HCl (two CONTRAVE 8 mg/90 mg tablets twice daily) is reached at the start of Week 4.

Removed in this revision

• -Removed: Recommended Dosing CONTRAVE dosing should be escalated according to the following schedule: A total daily dosage of two CONTRAVE 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4.
• -Removed: BMI is calculated by dividing weight (in kg) by height (in meters) squared.
• -Removed: A BMI chart for determining BMI based on height and weight is provided in Table 1.

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: CONTRAVE is not approved for use in pediatric patients.

Approved uses

Added in this revision

• +Added: RETIN-A MICRO ® is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older.

Removed in this revision

• -Removed: Retin-A Micro ® is a retinoid indicated for topical application in the treatment of acne vulgaris.

Dosage and administration

Added in this revision

• +Added: Not for oral, ophthalmic, or intravaginal use. • Prior to RETIN-A MICRO use, thoroughly cleanse area(s) with a mild, non-medicated cleanser then pat the skin dry. • When applying RETIN-A MICRO, keep away from the eyes, the mouth, paranasal creases of the nose, and mucous membranes. • Apply a thin layer of RETIN-A MICRO (0.04%, 0.06%, 0.08%, or 0.1%) to skin where acne lesions appear (cover the entire affected area), once daily in the evening.
• +Added: Do not apply more than a thin layer.
• +Added: Improvements in acne lesions may be noticed after two weeks of RETIN-A MICRO therapy, but more than seven weeks of therapy may be needed for sustained benefit.
• +Added: If RETIN-A MICRO was temporarily discontinued due to local adverse reactions, RETIN-A MICRO therapy may be resumed upon resolution of local adverse reactions.

Removed in this revision

• -Removed: Not for ophthalmic, oral, or intravaginal use.
• -Removed: Retin-A Micro should be applied once a day, in the evening, to the skin where acne lesions appear, using enough to cover the entire affected area in a thin layer.
• -Removed: Areas to be treated should be cleansed thoroughly before the medication is applied.
• -Removed: If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur.
• -Removed: A transitory feeling of warmth or slight stinging may be noted on application.
• -Removed: In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or the frequency of application increased as the patient becomes able to tolerate the treatment.
• -Removed: Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
• -Removed: Efficacy has not been established for less than once daily dosing frequencies.
• -Removed: During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur.
• -Removed: If tolerated, this should not be considered a reason to discontinue therapy.
• -Removed: Therapeutic results may be noticed after two weeks, but more than seven weeks of therapy are required before consistent beneficial effects are observed.
• -Removed: Retin-A Micro should be kept away from the eyes, the mouth, paranasal creases of the nose, and mucous membranes.
• -Removed: Patients treated with Retin-A Micro may use cosmetics.
• -Removed: Concomitant topical medication, medicated or abrasive soaps and cleansers, products that have a strong drying effect, products with high concentrations of alcohol, astringents, or spices should be used with caution because of possible interaction with tretinoin.
• -Removed: Avoid contact with the peel of limes.
• -Removed: Particular caution should be exercised with the concomitant use of topical over-the-counter acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with Retin-A Micro.
• -Removed: It also is advisable to allow the effects of such preparations to subside before use of Retin-A Micro is begun.

Forms and strengths

Added in this revision

• +Added: Gel (white to very pale yellow and opaque): • 0.04% (0.4 mg of tretinoin per gram) • 0.06% (0.6 mg of tretinoin per gram) • 0.08% (0.8 mg of tretinoin per gram) • 0.1% (1 mg of tretinoin per gram).

Removed in this revision

• -Removed: Retin-A Micro is a white to very pale yellow opaque gel.
• -Removed: Retin-A Micro is available in four strengths: 0.1%, 0.08%, 0.06% and 0.04%.
• -Removed: Each gram of Retin-A Micro Gel, 0.1%, contains 1 mg of tretinoin.
• -Removed: Each gram of Retin-A Micro Gel, 0.08%, contains 0.8 mg of tretinoin.
• -Removed: Each gram of Retin-A Micro Gel, 0.06%, contains 0.6 mg of tretinoin.
• -Removed: Each gram of Retin-A Micro Gel, 0.04%, contains 0.4 mg of tretinoin.

Warnings and precautions

This section was substantially rewritten in this revision: 16 entries added, 10 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.

1 entry reworded without a change of meaning.

Adverse reactions

This section was substantially rewritten in this revision: 18 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.

4 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: The percentage of subjects that had symptoms present before treatment (at baseline), during treatment, and the percent with symptoms present at Week 12 are shown in Table 1. *Mod. = Moderate Postmarketing Experience Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Removed in this revision

• -Removed: The percentage of subjects that had symptoms present before treatment (at baseline), during treatment, and the percent with symptoms present at Week 12 are shown in Table 1.
• -Removed: Postmarketing Experience Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Approved uses

Added in this revision

• +Added: RENOVA (tretinoin cream) 0.02% has NOT DEMONSTRATED A MITIGATING EFFECT on significant signs of chronic sunlight exposure such as coarse or deep wrinkling, tactile roughness, mottled hyperpigmentation, lentigines, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis.
• +Added: RENOVA (tretinoin cream) 0.02% should be used under medical supervision as an adjunct to a comprehensive skin care and sunlight avoidance program that includes the use of effective sunscreens (minimum SPF of 15) and protective clothing.
• +Added: Patients with visible actinic keratosis and patients with a history of skin cancer were excluded from clinical trials of RENOVA (tretinoin cream) 0.02%.
• +Added: Thus the effectiveness and safety of RENOVA (tretinoin cream) 0.02% in these populations are not known at this time.
• +Added: Neither the safety nor the effectiveness of RENOVA (tretinoin cream) 0.02% for the prevention or treatment of actinic keratoses or skin neoplasms has been established.
• +Added: Neither the safety nor the efficacy of using RENOVA (tretinoin cream) 0.02% daily for greater than 52 weeks has been established, and daily use beyond 52 weeks has not been systematically and histologically investigated in adequate and well-controlled trials (see WARNINGS).

Removed in this revision

• -Removed: Thus the effectiveness and safety of RENOVA (tretinoin cream) 0.02% in these populations are not known at this time. • Neither the safety nor the effectiveness of RENOVA (tretinoin cream) 0.02% for the prevention or treatment of actinic keratoses or skin neoplasms has been established. • Neither the safety nor the efficacy of using RENOVA (tretinoin cream) 0.02% daily for greater than 52 weeks has been established, and daily use beyond 52 weeks has not been systematically and histologically...

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is pregnant or is attempting to become pregnant or is at high risk of pregnancy.
• +Added: Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is sunburned or if the patient has eczema or other chronic skin conditions of the face.
• +Added: Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is inherently sensitive to sunlight.
• +Added: Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is also taking drug(s) known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity.

Removed in this revision

• -Removed: • Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is pregnant or is attempting to become pregnant or is at high risk of pregnancy. • Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is sunburned or if the patient has eczema or other chronic skin conditions of the face. • Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is inherently sensitive to sunlight. • Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is also taking drug(s) known to be photosensitizers...

Warnings

Added in this revision

• +Added: The significance of these findings and their relevance for RENOVA (tretinoin cream) 0.02% are unknown.

1 entry reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: Limitations of Use MOUNJARO has not been studied in patients with a history of pancreatitis.
• -Removed: MOUNJARO is not indicated for use in patients with type 1 diabetes mellitus.

Warnings and precautions

Added in this revision

• +Added: 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, or MOUNJARO.
• +Added: The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea.
• +Added: Monitor renal function in patients reporting adverse reactions to MOUNJARO that could lead to volume depletion, especially during dosage initiation and escalation of MOUNJARO.
• +Added: MOUNJARO is not recommended in patients with severe gastroparesis.

Removed in this revision

• -Removed: In clinical studies, 14 events of acute pancreatitis were confirmed by adjudication in 13 MOUNJARO-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure).
• -Removed: MOUNJARO has not been studied in patients with a prior history of pancreatitis.
• -Removed: It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on MOUNJARO.
• -Removed: Acute Kidney Injury MOUNJARO has been associated with gastrointestinal adverse reactions, which include nausea, vomiting, and diarrhea.
• -Removed: These events may lead to dehydration, which if severe could cause acute kidney injury.
• -Removed: In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis.
• -Removed: Some of these events have been reported in patients without known underlying renal disease.
• -Removed: A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.
• -Removed: Monitor renal function when initiating or escalating doses of MOUNJARO in patients with renal impairment reporting severe gastrointestinal adverse reactions.
• -Removed: MOUNJARO has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.

1 entry reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: SAXENDA 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 and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. • Adults with overweight in the presence of at least one weight-related comorbid condition.
• +Added: Limitations of Use • SAXENDA contains liraglutide.
• +Added: Coadministration with other liraglutide-containing products or with any other glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended. • The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been established.

Removed in this revision

• -Removed: SAXENDA is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: • Adult patients with an initial body mass index (BMI) of: ▪ 30 kg/m 2 or greater (obese), or ▪ 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) • Pediatric patients aged 12 years and older with: ▪ body weight above 60 kg and ▪ an initial BMI corresponding...

Dosage and administration

Added in this revision

• +Added: Important Administration Instructions • Prior to initiation of SAXENDA, train patients on proper injection technique.
• +Added: Then follow the dosage escalation schedule in Table 1 to reduce the risk of gastrointestinal adverse reactions.

Removed in this revision

• -Removed: Patient Selection Select patients for SAXENDA treatment as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management based on the BMI values provided in Tables 1 and 2.
• -Removed: Adult and Pediatric Patients BMI is calculated by dividing weight in (kilograms) by height (in meters) squared.
• -Removed: A chart for determining BMI based on height and weight is provided in Table 1.
• -Removed: Table 1: BMI Conversion Chart Pediatric Patients Aged 12 Years and Older BMI cut-offs for obesity in pediatric patients aged 12 years and older are presented in Table 2.
• -Removed: Table 2: International Obesity Task Force BMI Cut-offs for Obesity by Sex and Age for Pediatric Patients Aged 12 Years and Older (Cole Criteria) Important Administration Instructions • Prior to initiation of SAXENDA, train patients on proper injection technique.
• -Removed: Then follow the dose escalation schedule in Table 3 to minimize gastrointestinal adverse reactions.

6 entries reworded without a change of meaning.

Forms and strengths

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: If pancreatitis is suspected, discontinue SAXENDA and initiate appropriate management.
• +Added: 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 liraglutide.
• +Added: The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea.
• +Added: Monitor renal function in patients reporting adverse reactions to SAXENDA that could lead to volume depletion, especially during dosage initiation and escalation.
• +Added: Severe Gastrointestinal Adverse Reactions Use of GLP-1 receptor agonists, including liraglutide, has been associated with gastrointestinal adverse reactions, sometimes severe.
• +Added: In SAXENDA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving SAXENDA (4.8%) than placebo (1.4%).
• +Added: SAXENDA is not recommended in patients with severe gastroparesis.

Removed in this revision

• -Removed: If pancreatitis is suspected, SAXENDA should promptly be discontinued and appropriate management should be initiated.
• -Removed: If pancreatitis is confirmed, SAXENDA should not be restarted.
• -Removed: In SAXENDA clinical trials in adults, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 SAXENDA-treated patients and 2 (0.1%) of 1843 placebo-treated patients.
• -Removed: In addition, there were 2 cases of acute pancreatitis in SAXENDA-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose.
• -Removed: There were 2 additional cases in SAXENDA-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing SAXENDA, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days.
• -Removed: In a SAXENDA pediatric clinical trial, pancreatitis was not independently adjudicated.
• -Removed: Pancreatitis was reported in 1 (0.8%) SAXENDA-treated patient and resulted in treatment discontinuation.
• -Removed: Liraglutide has been studied in a limited number of adult patients with a history of pancreatitis.
• -Removed: It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on SAXENDA.
• -Removed: Renal Impairment In patients treated with GLP-1 receptor agonists, including SAXENDA, there have been reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis.
• -Removed: Some of these events were reported in patients without known underlying renal disease.
• -Removed: A majority of the reported events occurred in patients who had experienced nausea, vomiting, or diarrhea leading to volume depletion.
• -Removed: Some of the reported events occurred in patients receiving one or more medications known to affect renal function or volume status.
• -Removed: Altered renal function has been reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative agents, including liraglutide.
• -Removed: Use caution when initiating or escalating doses of SAXENDA in patients with renal impairment.

1 entry reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Acute Pancreatitis In SAXENDA clinical trials in adults, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 SAXENDA-treated patients and 2 (0.1%) of 1843 placebo-treated patients.
• +Added: In addition, there were 2 cases of acute pancreatitis in SAXENDA-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose.
• +Added: There were 2 additional cases in SAXENDA-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing SAXENDA, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days.
• +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: Severe gastrointestinal adverse reactions were reported more frequently among patients receiving SAXENDA (4.8%) than placebo (1.4%).
• +Added: Gastrointestinal acute pancreatitis; hemorrhagic and necrotizing pancreatitis, sometimes resulting in death; ileus, nausea, vomiting and diarrhea leading to dehydration Hepatobiliary hyperbilirubinemia, elevations of liver enzymes, cholestasis and hepatitis Hypersensitivity rash, pruritus, angioedema and anaphylactic reactions Neoplasms medullary thyroid carcinoma Neurologic dysesthesia Pulmonary Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective...
• +Added: Renal Acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis; increased serum creatinine General Disorders and Administration Site Conditions Allergic reactions: rash and pruritus Immune System Angioedema and anaphylactic reactions Skin and Subcutaneous Tissue Cutaneous amyloidosis, alopecia

Removed in this revision

• -Removed: Neoplasms Medullary thyroid carcinoma Gastrointestinal Disorders Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death, ileus Metabolism and Nutrition Disorders Dehydration resulting from nausea, vomiting and diarrhea Renal and Urinary Disorders Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis General Disorders and Administration Site Conditions Allergic reactions: rash and pruritus...

9 entries reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: Limitations of Use: VICTOZA contains liraglutide.
• +Added: Coadministration with other liraglutide-containing products is not recommended.

Removed in this revision

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

Dosage and administration

3 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including VICTOZA.
• +Added: If pancreatitis is suspected, discontinue VICTOZA and initiate appropriate management.
• +Added: 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 VICTOZA.
• +Added: The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea.
• +Added: Monitor renal function in patients reporting adverse reactions to VICTOZA that could lead to volume depletion, especially during dosage initiation and escalation of VICTOZA..
• +Added: Severe Gastrointestinal Adverse Reactions Use of GLP-1 receptor agonists, including VICTOZA, has been associated with gastrointestinal adverse reactions, sometimes severe.
• +Added: In VICTOZA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving VICTOZA (1.2 mg 4.4%, 1.8 mg 4.2%) than placebo (1.1%).
• +Added: VICTOZA is not recommended in patients with severe gastroparesis.

Removed in this revision

• -Removed: Pancreatitis Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with VICTOZA.
• -Removed: If pancreatitis is suspected, VICTOZA should promptly be discontinued and appropriate management should be initiated.
• -Removed: If pancreatitis is confirmed, VICTOZA should not be restarted.
• -Removed: In glycemic control trials of VICTOZA, there have been 13 cases of pancreatitis among VICTOZA-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0.5 cases per 1000 patient-years).
• -Removed: Nine of the 13 cases with VICTOZA were reported as acute pancreatitis and four were reported as chronic pancreatitis.
• -Removed: In one case in a VICTOZA-treated patient, pancreatitis, with necrosis, was observed and led to death; however clinical causality could not be established.
• -Removed: Some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.
• -Removed: VICTOZA has been studied in a limited number of patients with a history of pancreatitis.
• -Removed: It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on VICTOZA.
• -Removed: Acute Kidney Injury VICTOZA has not been found to be directly nephrotoxic in animal studies or clinical trials.
• -Removed: There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis in VICTOZA-treated patients.
• -Removed: Some of these events were reported in patients without known underlying renal disease.
• -Removed: A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.
• -Removed: Some of the reported events occurred in patients receiving one or more medications known to affect renal function or hydration status.
• -Removed: Altered renal function has been reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative agents, including VICTOZA.
• -Removed: Use caution when initiating or escalating doses of VICTOZA in patients with renal impairment.

Adverse reactions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions were reported more frequently among patients receiving VICTOZA (1.2 mg 4.4%, 1.8 mg 4.2%) than placebo (1.1%).
• +Added: Pancreatitis In glycemic control trials of VICTOZA, there have been 13 cases of pancreatitis among VICTOZA-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0.5 cases per 1000 patient-years).
• +Added: Nine of the 13 cases with VICTOZA were reported as acute pancreatitis and four were reported as chronic pancreatitis.
• +Added: In one case in a VICTOZA-treated patient, pancreatitis, with necrosis, was observed and led to death; however clinical causality could not be established.
• +Added: Some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.

3 entries reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: Limitations of Use TRULICITY: Has not been studied in patients with a history of pancreatitis.
• -Removed: Consider other antidiabetic therapies in patients with a history of pancreatitis.
• -Removed: Should not be used in patients with type 1 diabetes mellitus.
• -Removed: Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients.

Warnings and precautions

Added in this revision

• +Added: 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.
• +Added: 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.
• +Added: The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea.
• +Added: Monitor renal function in patients reporting adverse reactions to TRULICITY that could lead to volume depletion, especially during dosage initiation and escalation of TRULICITY.
• +Added: TRULICITY is not recommended in patients with severe gastroparesis.

Removed in this revision

• -Removed: Pancreatitis In a pooled analysis from the original registration studies, 12 (3.4 cases per 1000 patient years) pancreatitis-related adverse reactions were reported in patients exposed to TRULICITY versus 3 in non-incretin comparators (2.7 cases per 1000 patient years).
• -Removed: An analysis of adjudicated events revealed 5 cases of confirmed pancreatitis in patients exposed to TRULICITY (1.4 cases per 1000 patient years) versus 1 case in non-incretin comparators (0.88 cases per 1000 patient years).
• -Removed: Based on an analysis of adjudicated events in a clinical trial 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%).
• -Removed: If pancreatitis is confirmed, TRULICITY should not be restarted.
• -Removed: TRULICITY has not been evaluated in patients with a prior history of pancreatitis.
• -Removed: Consider other antidiabetic therapies in patients with a history of pancreatitis.
• -Removed: 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.
• -Removed: Some of these events were reported in patients without known underlying renal disease.
• -Removed: A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.
• -Removed: Because these reactions may worsen renal function, use caution when initiating or escalating doses of TRULICITY in patients with renal impairment.
• -Removed: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions.
• -Removed: TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.

1 entry reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Fixed Drug Eruption Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption.
• +Added: If severe reactions occur, discontinue ORACEA immediately and initiate appropriate therapy.

Warnings and precautions

Added in this revision

• +Added: Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption.
• +Added: If severe skin reactions occur, discontinue DORYX MPC immediately and institute appropriate therapy.

Removed in this revision

• -Removed: If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.

Adverse reactions

Added in this revision

• +Added: Psychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination

1 entry reworded without a change of meaning.

Drug interactions

Removed in this revision

• -Removed: Penthrane The concurrent use of tetracycline and Penthrane ® (methoxyflurane) has been reported to result in fatal renal toxicity.

Forms and strengths

Removed in this revision

• -Removed: Metformin Hydrochloride Tablets USP, 850 mg: White, biconvex, circular shaped film coated tablets with 'A' debossed on one side and '13' debossed on the other side.
• -Removed: Metformin Hydrochloride Tablets USP, 1000 mg: White, biconvex, oval shaped film coated tablets with a score line in between '1' and '4' on one side and 'A' debossed on the other side.

Approved uses

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Recommended Dose Escalation Schedule The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks.
• +Added: Recommended Maintenance and Maximum Dosage Recommended Maintenance Dosage Weight Reduction and Long-Term Maintenance The recommended maintenance dosage is 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.
• +Added: OSA The recommended maintenance dosage is 10 mg or 15 mg injected subcutaneously once weekly.

Removed in this revision

• -Removed: Recommended Dosage The recommended starting dosage of ZEPBOUND is 2.5 mg injected subcutaneously once weekly.
• -Removed: The recommended maintenance dosages of ZEPBOUND in adults are 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Similar rates of severe gastrointestinal adverse reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND clinical trials for OSA.
• +Added: Similar rates of cholelithiasis were reported in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA.
• +Added: The exposure-adjusted incidence rate for treatment-emergent adjudication-confirmed pancreatitis in the pooled clinical studies for OSA (Studies 5 and 6) was 0.84 patients per 100 years for ZEPBOUND and 0 for placebo-treated patients.
• +Added: Continuation of ZEPBOUND after a confirmed diagnosis of pancreatitis should be individually determined in the clinical judgment of a patient's health care provider.
• +Added: Similar rates of severe hypersensitivity reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA.

Removed in this revision

• -Removed: ZEPBOUND has not been studied in patients with a prior history of pancreatitis.
• -Removed: It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on ZEPBOUND.
• -Removed: If the diagnosis of pancreatitis is confirmed, ZEPBOUND should not be restarted.

4 entries reworded without a change of meaning.