What the FDA changed in 2015

Approved uses

7 entries reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.;
• +Added: Swallow immediately. • PREVACID Delayed-Release Capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows: Open capsule.;
• +Added: Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL - approximately two ounces).;
• +Added: Swallow immediately.;
• +Added: To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
• +Added: Mix intact granules into 40 mL of apple juice.
• +Added: DO NOT USE OTHER LIQUIDS.;
• +Added: Inject through the nasogastric tube into the stomach.;
• +Added: Flush with additional apple juice to clear the tube.
• +Added: PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets • PREVACID SoluTab should not be broken or cut. • PREVACID SoluTab should not be chewed.;
• +Added: Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed.;
• +Added: The tablet typically disintegrates in less than one minute.;
• +Added: Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID SoluTab can be delivered in two different ways.

Removed in this revision

• -Removed: DO NOT USE OTHER LIQUIDS. • Inject through the nasogastric tube into the stomach. • Flush with additional apple juice to clear the tube.
• -Removed: PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets • PREVACID SoluTab should not be broken or cut. • PREVACID SoluTab should not be chewed. • Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed. • The tablet typically disintegrates in less than 1 minute. • Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID SoluTab can be delivered in two different ways.

3 entries reworded without a change of meaning.

Drug interactions

4 entries reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: 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 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...

Removed in this revision

• -Removed: 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.
• -Removed: 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.
• -Removed: Patients with visible actinic keratoses and patients with a history of skin cancer were excluded from clinical trials of RENOVA ® (tretinoin cream) 0.02%.
• -Removed: Thus the effectiveness and safety of RENOVA ® (tretinoin cream) 0.02% in these populations are not known at this time.
• -Removed: 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.
• -Removed: Neither the safety nor the efficacy of 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.

1 entry reworded without a change of meaning.

Dosage and administration

1 entry reworded without a change of meaning.

Warnings

Removed in this revision

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

1 entry reworded without a change of meaning.

Adverse reactions

Removed in this revision

• -Removed: Adverse reactions reported in greater than or equal to 2% of Saxenda-treated patients and more frequently than in placebo-treated patients are shown in Table 3. 1.

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: 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: 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.
• +Added: 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.
• +Added: Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with TRULICITY.

Removed in this revision

• -Removed: It is unknown whether TRULICITY will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of this signal could not be determined from the clinical or nonclinical studies.
• -Removed: The role of serum calcitonin monitoring or thyroid ultrasound monitoring for the purpose of early detection of MTC in patients treated with TRULICITY is unknown.

5 entries reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: Important Limitations of Use • Victoza is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans.
• +Added: Prescribe Victoza only to patients for whom the potential benefits are considered to outweigh the potential risk. • 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 in this revision

• -Removed: Important Limitations of Use ▪ Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, prescribe Victoza only to patients for whom the potential benefits are considered to outweigh the potential risk.
• -Removed: Victoza is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. ▪ Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been observed in patients treated with Victoza.

Contraindications

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Cases of MTC in patients treated with Victoza have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and Victoza use in humans.
• +Added: Victoza is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2.
• +Added: Counsel patients regarding the potential risk for MTC with the use of Victoza and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
• +Added: Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza.
• +Added: Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L.
• +Added: If serum calcitonin is measured and found to be elevated, the patient should be further evaluated.
• +Added: Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

Removed in this revision

• -Removed: A statistically significant increase in cancer was observed in rats receiving liraglutide at 8-times clinical exposure compared to controls.
• -Removed: In the clinical trials, there have been 6 reported cases of thyroid C-cell hyperplasia among Victoza-treated patients and 2 cases in comparator-treated patients (1.3 vs. 1.0 cases per 1000 patient-years).
• -Removed: One comparator-treated patient with MTC had pre-treatment serum calcitonin concentrations >1000 ng/L suggesting pre-existing disease.
• -Removed: All of these cases were diagnosed after thyroidectomy, which was prompted by abnormal results on routine, protocol-specified measurements of serum calcitonin.
• -Removed: Five of the six Victoza-treated patients had elevated calcitonin concentrations at baseline and throughout the trial.
• -Removed: One Victoza and one non-Victoza-treated patient developed elevated calcitonin concentrations while on treatment.
• -Removed: Calcitonin, a biological marker of MTC, was measured throughout the clinical development program.
• -Removed: The serum calcitonin assay used in the Victoza clinical trials had a lower limit of quantification (LLOQ) of 0.7 ng/L and the upper limit of the reference range was 5.0 ng/L for women and 8.4 ng/L for men.
• -Removed: At Weeks 26 and 52 in the clinical trials, adjusted mean serum calcitonin concentrations were higher in Victoza-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator.
• -Removed: At these timepoints, the adjusted mean serum calcitonin values (~ 1.0 ng/L) were just above the LLOQ with between-group differences in adjusted mean serum calcitonin values of approximately 0.1 ng/L or less.
• -Removed: Among patients with pre-treatment serum calcitonin below the upper limit of the reference range, shifts to above the upper limit of the reference range which persisted in subsequent measurements occurred most frequently among patients treated with Victoza 1.8 mg/day.
• -Removed: In trials with on-treatment serum calcitonin measurements out to 5-6 months, 1.9% of patients treated with Victoza 1.8 mg/day developed new and persistent calcitonin elevations above the upper limit of the reference range compared to 0.8-1.1% of patients treated with control medication or the 0.6 and 1.2 mg doses of Victoza.
• -Removed: In trials with on-treatment serum calcitonin measurements out to 12 months, 1.3% of patients treated with Victoza 1.8 mg/day had new and persistent elevations of calcitonin from below or within the reference range to above the upper limit of the reference range, compared to 0.6%, 0% and 1.0% of patients treated with Victoza 1.2 mg, placebo and active control, respectively.
• -Removed: Otherwise, Victoza did not produce consistent dose-dependent or time-dependent increases in serum calcitonin.
• -Removed: Patients with MTC usually have calcitonin values >50 ng/L.
• -Removed: In Victoza clinical trials, among patients with pre-treatment serum calcitonin <50 ng/L, one Victoza-treated patient and no comparator-treated patients developed serum calcitonin >50 ng/L.
• -Removed: The Victoza-treated patient who developed serum calcitonin >50 ng/L had an elevated pre-treatment serum calcitonin of 10.7 ng/L that increased to 30.7 ng/L at Week 12 and 53.5 ng/L at the end of the 6-month trial.
• -Removed: Follow-up serum calcitonin was 22.3 ng/L more than 2.5 years after the last dose of Victoza.
• -Removed: The largest increase in serum calcitonin in a comparator-treated patient was seen with glimepiride in a patient whose serum calcitonin increased from 19.3 ng/L at baseline to 44.8 ng/L at Week 65 and 38.1 ng/L at Week 104.
• -Removed: Among patients who began with serum calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of Victoza-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients, with an incidence of 1.1% among patients treated with 1.8 mg/day of Victoza.
• -Removed: The clinical significance of these findings is unknown.
• -Removed: Counsel patients regarding the risk for MTC and the symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness).
• -Removed: Patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinologist for further evaluation.
• -Removed: Although routine monitoring of serum calcitonin is of uncertain value in patients treated with Victoza, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

2 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors • Pancreatitis • Use with Medications Known to Cause Hypoglycemia • Renal Impairment • Hypersensitivity Reactions Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may...
• +Added: Calcitonin Calcitonin, a biological marker of MTC, was measured throughout the clinical development program.
• +Added: At the end of the clinical trials, adjusted mean serum calcitonin concentrations were higher in Victoza-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator.
• +Added: Between group differences in adjusted mean serum calcitonin values were approximately 0.1 ng/L or less.
• +Added: Among patients with pretreatment calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of Victoza-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients.
• +Added: The clinical significance of these findings is unknown.

Removed in this revision

• -Removed: Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

2 entries reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: Victoza is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.
• -Removed: Victoza is not a substitute for insulin.
• -Removed: The concurrent use of Victoza and prandial insulin has not been studied.

3 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Never Share a Victoza Pen Between Patients Victoza pens must never be shared between patients, even if the needle is changed.
• +Added: Pen-sharing poses a risk for transmission of blood-borne pathogens.

Approved uses

1 entry reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.

Warnings and precautions

Added in this revision

• +Added: Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including PREVACID.
• +Added: Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.
• +Added: Discontinue PREVACID if acute interstitial nephritis develops.
• +Added: Cyanocobalamin (vitamin B12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria.
• +Added: Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature.
• +Added: This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

Drug interactions

Added in this revision

• +Added: Drugs with pH-Dependent Absorption Kinetics Due to its effects on gastric acid secretion, lansoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability.
• +Added: Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ampicillin esters, ketoconazole, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with PREVACID.
• +Added: Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH.
• +Added: The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and MMF.
• +Added: Use PREVACID with caution in transplant patients receiving MMF.

Removed in this revision

• -Removed: Drugs with pH-Dependent Absorption Kinetics PREVACID causes long-lasting inhibition of gastric acid secretion.
• -Removed: PREVACID and other PPIs may interfere with the absorption of other drugs where gastric pH is an important determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole).

3 entries reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.

Warnings and precautions

Added in this revision

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

Drug interactions

Added in this revision

• +Added: Drugs for Which Gastric pH Can Affect Bioavailability Due to its effects on gastric acid secretion, pantoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability.
• +Added: Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease.
• +Added: Co-administration of pantoprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH.
• +Added: The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PROTONIX and MMF.
• +Added: Use PROTONIX with caution in transplant patients receiving MMF.

Removed in this revision

• -Removed: Drugs for Which Gastric pH Can Affect Bioavailability Pantoprazole causes long-lasting inhibition of gastric acid secretion.
• -Removed: Therefore, pantoprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts).

1 entry reworded without a change of meaning.

Dosage and administration

1 entry reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: NEXIUM is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation.
• +Added: Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.

Removed in this revision

• -Removed: NEXIUM is contraindicated in patients with known hypersensitivity to proton pump inhibitors.
• -Removed: Hypersensitivity reactions, e.g., angioedema and anaphylactic shock, have been reported with NEXIUM use.

Warnings and precautions

Added in this revision

• +Added: Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including NEXIUM.
• +Added: Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction.
• +Added: Discontinue NEXIUM if acute interstitial nephritis develops.
• +Added: Cyanocobalamin (vitamin B-12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria.
• +Added: Rare reports of cyanocobalamin deficiency occurring with acid-supressing therapy have been reported in the literature.
• +Added: This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

2 entries reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: Drugs for Which Gastric pH Can Affect Bioavailability Due to its effects on gastric acid secretion, esomeprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability.
• +Added: Co-administration of omeprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH.
• +Added: The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving NEXIUM and MMF.
• +Added: Use NEXIUM with caution in transplant patients receiving MMF.

Removed in this revision

• -Removed: Drugs for Which Gastric pH Can Affect Bioavailability Esomeprazole inhibits gastric acid secretion.
• -Removed: Therefore, esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability.

3 entries reworded without a change of meaning.