What the FDA changed in 2017

Warnings and precautions

Added in this revision

• +Added: On average, serum creatinine gradually declined but remained elevated over baseline creatinine values Elevations in serum creatinine often signify a decrease in renal function, but the cause for Qsymia-associated changes in serum creatinine has not been definitively established..Therefore, measurement of serum creatinine prior to starting Qsymia and during Qsymia treatment is recommended.

Removed in this revision

• -Removed: Elevation in Creatinine Qsymia can cause an increase in serum creatinine.
• -Removed: On average, serum creatinine gradually declined but remained elevated over baseline creatinine values.
• -Removed: Elevations in serum creatinine often signify a decrease in renal function, but the cause for Qsymia-associated changes in serum creatinine has not been definitively established.
• -Removed: Therefore, measurement of serum creatinine prior to starting Qsymia and during Qsymia treatment is recommended.

1 entry reworded without a change of meaning.

Approved uses

2 entries reworded without a change of meaning.

Forms and strengths

1 entry reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: Proton pump inhibitors (PPIs), including PROTONIX, are contraindicated in patients receiving rilpivirine-containing products.

Warnings and precautions

Added in this revision

• +Added: Interference with Urine Screen for THC There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including PROTONIX.

Removed in this revision

• -Removed: Interference with Urine Screen for THC See Drug Interactions.
• -Removed: Interference with Laboratory Tests Use of PPIs, including pantoprazole, may increase chromogranin A (CgA) levels which may interfere with investigations for neuroendocrine tumors.
• -Removed: To avoid this interference, PPI treatment should be stopped 14 days before CgA measurements.

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: Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PROTONIX and instructions for preventing or managing them.
• +Added: Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Removed in this revision

• -Removed: Interference with Antiretroviral Therapy Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended.
• -Removed: Co-administration of atazanavir or nelfinavir with proton pump inhibitors is expected to substantially decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and development of drug resistance.
• -Removed: Coumarin Anticoagulants There have been postmarketing reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including PROTONIX, and warfarin concomitantly.
• -Removed: Increases in INR and prothrombin time may lead to abnormal bleeding and even death.
• -Removed: Patients treated with proton pump inhibitors and warfarin concomitantly should be monitored for increases in INR and prothrombin time.
• -Removed: Clopidogrel Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition.
• -Removed: No dose adjustment of clopidogrel is necessary when administered with an approved dose of PROTONIX.
• -Removed: 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.
• -Removed: 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.
• -Removed: 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.
• -Removed: The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PROTONIX and MMF.
• -Removed: Use PROTONIX with caution in transplant patients receiving MMF.
• -Removed: False Positive Urine Tests for THC There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving proton pump inhibitors.
• -Removed: An alternative confirmatory method should be considered to verify positive results.
• -Removed: Methotrexate Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate.
• -Removed: However, no formal drug interaction studies of Methotrexate with PPIs have been conducted.

Approved uses

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Patients treated with Retin-A Micro may use cosmetics.

Removed in this revision

• -Removed: Patients treated with Retin-A Micro® (tretinoin) Gel microsphere, 0.1%, 0.08% and 0.04% may use cosmetics.

4 entries reworded without a change of meaning.

Forms and strengths

Added in this revision

• +Added: Retin-A Micro is available in four strengths: 0.1%, 0.08%, 0.06% and 0.04%.
• +Added: Each gram of Retin-A Micro Gel, 0.06%, contains 0.6 mg of tretinoin.

Removed in this revision

• -Removed: Retin-A Micro is available in three strengths: 0.04%, 0.08% and 0.1%.

Warnings and precautions

2 entries reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: Maintenance of Healed Duodenal Ulcers PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of duodenal ulcers.
• +Added: Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) PREVACID and PREVACID SoluTab are indicated in adults and pediatric patients one year of age and older for the treatment of heartburn and other symptoms associated with GERD for up to eight weeks.
• +Added: Treatment of Erosive Esophagitis (EE) PREVACID and PREVACID SoluTab are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of EE.
• +Added: Maintenance of Healing of EE PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of EE.

Removed in this revision

• -Removed: Maintenance of Healed Duodenal Ulcers PREVACID is indicated to maintain healing of duodenal ulcers.
• -Removed: Gastroesophageal Reflux Disease (GERD) Short-Term Treatment of Symptomatic GERD PREVACID is indicated for the treatment of heartburn and other symptoms associated with GERD for up to eight weeks.
• -Removed: Short-Term Treatment of Erosive Esophagitis PREVACID is indicated for short-term treatment (up to eight weeks) for healing and symptom relief of all grades of erosive esophagitis.
• -Removed: Maintenance of Healing of Erosive Esophagitis (EE) PREVACID is indicated to maintain healing of erosive esophagitis.

9 entries reworded without a change of meaning.

Dosage and administration

This section was substantially rewritten in this revision: 21 entries added, 22 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.

6 entries reworded without a change of meaning.

Forms and strengths

Added in this revision

• +Added: PREVACID delayed-release capsules: 15 mg strength is an opaque, pink and green capsule imprinted with TAP and "PREVACID 15". 30 mg strength is an opaque, pink and black capsule imprinted with TAP and "PREVACID 30".
• +Added: PREVACID SoluTab delayed-release orally disintegrating tablets: 15 mg strength is a white to yellowish white, uncoated round tablet containing orange to dark brown speckles with "15" debossed on one side. 30 mg strength is a white to yellowish white, uncoated round tablet containing orange to dark brown speckles with "30" debossed on one side.

Removed in this revision

• -Removed: 15 mg capsules are opaque, hard gelatin, colored pink and green with the TAP logo and "PREVACID 15" imprinted on the capsule. 30 mg capsules are opaque, hard gelatin, colored pink and black with the TAP logo and "PREVACID 30" imprinted on the capsule. 15 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "15" debossed on one side of the tablet. 30 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "30"...

Contraindications

Added in this revision

• +Added: Proton Pump Inhibitors (PPIs), including PREVACID and PREVACID SoluTab, are contraindicated with rilpivirine-containing products.

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Discontinue PREVACID or PREVACID SoluTab if acute interstitial nephritis develops.
• +Added: Interactions with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity.
• +Added: The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors.
• +Added: Healthcare providers should temporarily stop lansoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high.
• +Added: If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.
• +Added: Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU).
• +Added: PREVACID SoluTab contains phenylalanine, a component of aspartame.
• +Added: Each 15 mg tablet contains 2.5 mg and each 30 mg tablet contains 5.1 mg of phenylalanine.
• +Added: Before prescribing PREVACID SoluTab to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including PREVACID SoluTab.

Removed in this revision

• -Removed: Discontinue PREVACID if acute interstitial nephritis develops.

9 entries reworded without a change of meaning.

Adverse reactions

7 entries reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: Tables 2 and 3 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PREVACID or PREVACID SoluTab and instructions for preventing or managing them.
• +Added: Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Removed in this revision

• -Removed: Drugs with pH-Dependent Absorption 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.
• -Removed: As with other drugs that decrease the intragastric acidity, the absorption of drugs such as ampicillin esters, ketoconazole, atazanavir, nelfinavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with PREVACID.
• -Removed: PREVACID is likely to substantially decrease the systemic concentrations of HIV protease inhibitors, such as atazanavir and nelfinavir, which are dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir or nelfinavir and the development of HIV resistance.
• -Removed: Therefore, PREVACID should not be co-administered with atazanavir or nelfinavir.
• -Removed: 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.
• -Removed: The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and MMF.
• -Removed: Use PREVACID with caution in transplant patients receiving MMF.
• -Removed: Warfarin In a study of healthy subjects, co-administration of single or multiple 60 mg doses of PREVACID and warfarin did not affect the pharmacokinetics of warfarin nor prothrombin time.
• -Removed: However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly.
• -Removed: Increases in INR and prothrombin time may lead to abnormal bleeding and even death.
• -Removed: Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
• -Removed: Tacrolimus Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
• -Removed: Theophylline A minor increase (10%) in the clearance of theophylline was observed following the administration of PREVACID concomitantly with theophylline.
• -Removed: Although the magnitude of the effect on theophylline clearance is small, individual patients may require additional titration of their theophylline dosage when PREVACID is started or stopped to ensure clinically effective blood levels.
• -Removed: Clopidogrel Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition.
• -Removed: No dose adjustment of clopidogrel is necessary when administered with an approved dose of PREVACID.
• -Removed: Methotrexate Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate.
• -Removed: However, no formal drug interaction studies of high dose methotrexate with PPIs have been conducted.
• -Removed: In a study of rheumatoid arthritis patients receiving low-dose methotrexate, PREVACID and naproxen, no effect on pharmacokinetics of methotrexate was observed.
• -Removed: Combination Therapy with Clarithromycin Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions.
• -Removed: Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs.
• -Removed: For information about drug interactions of antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID, refer to the DRUG INTERACTIONS section of their prescribing information.

Adverse reactions

Added in this revision

• +Added: In postmarketing use with Soolantra, occurrences of contact dermatitis and allergic dermatitis have been reported.

Approved uses

Added in this revision

• +Added: VICTOZA 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 and established cardiovascular disease.
• +Added: Limitations of Use: • VICTOZA is not a substitute for insulin.

Removed in this revision

• -Removed: VICTOZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• -Removed: 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.
• -Removed: 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: VICTOZA has not been studied in patients with a history of pancreatitis.
• -Removed: It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using VICTOZA.
• -Removed: Other antidiabetic therapies should be considered in patients with a history of pancreatitis. • VICTOZA is not a substitute for insulin.

Contraindications

Added in this revision

• +Added: Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with VICTOZA.

Warnings and precautions

Added in this revision

• +Added: VICTOZA has been studied in a limited number of patients with a history of pancreatitis.
• +Added: It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on VICTOZA.
• +Added: If a hypersensitivity reaction occurs, discontinue VICTOZA; treat promptly per standard of care, and monitor until signs and symptoms resolve.
• +Added: Do not use in patients with a previous hypersensitivity reaction to VICTOZA.
• +Added: Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists.
• +Added: Acute Gallbladder Disease In the LEADER trial, 3.1% of Victoza-treated patients versus 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis.
• +Added: The majority of events required hospitalization or cholecystectomy.
• +Added: If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

Removed in this revision

• -Removed: Consider antidiabetic therapies other than VICTOZA in patients with a history of pancreatitis.
• -Removed: If a hypersensitivity reaction occurs, the patient should discontinue VICTOZA and other suspect medications and promptly seek medical advice.
• -Removed: Angioedema has also been reported with other GLP-1 receptor agonists.
• -Removed: Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with VICTOZA or any other antidiabetic drug.

2 entries reworded without a change of meaning.

Adverse reactions

This section was substantially rewritten in this revision: 12 entries added, 11 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.

13 entries reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with TRULICITY.

Removed in this revision

• -Removed: Hypersensitivity TRULICITY is contraindicated in patients with a 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: If a hypersensitivity reaction occurs, discontinue TRULICITY; treat promptly per standard of care, and monitor until signs and symptoms resolve.
• +Added: Do not use in patients with a previous hypersensitivity reaction to TRULICITY.

Removed in this revision

• -Removed: If a hypersensitivity reaction occurs, the patient should discontinue TRULICITY and other suspected medications and promptly seek medical advice.

1 entry reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Anaphylactic reactions, angioedema.

Removed in this revision

• -Removed: Anaphylactic reactions.

Dosage and administration

Added in this revision

• +Added: If gastric irritation occurs, DORYX MPC may be given with food or milk.

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: Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood.
• +Added: Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication.
• +Added: Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses.
• +Added: Advise patients and caregivers that the patient should stop taking CONTRAVE and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.
• +Added: In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported.
• +Added: However, the symptoms persisted in some cases, therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

Removed in this revision

• -Removed: Instruct patients to contact a healthcare professional if such reactions occur.
• -Removed: In many of these cases, a causal relationship to bupropion treatment is not certain, because depressed mood can be a symptom of nicotine withdrawal.

4 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Postmarketing Experience Additional adverse reactions have been identified during post approval use of CONTRAVE.
• +Added: Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• +Added: Loss of consciousness, malaise

1 entry reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: Digoxin Coadministration of CONTRAVE with digoxin may decrease plasma digoxin levels.
• +Added: Monitor plasma digoxin levels in patients treated concomitantly with CONTRAVE and digoxin.

Warnings and precautions

Added in this revision

• +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.

5 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: In one of the 56-week trials, a subset of patients (with abnormal glucose measurements at randomization) were enrolled for a placebo-controlled 160-week period instead, followed by a 12-week off-treatment follow-up.
• +Added: For those participating in this 160-week period, patients received Saxenda for a mean treatment duration of 110 weeks (median, 159 weeks).
• +Added: T2DM = type 2 diabetes mellitus * Adverse reactions for trials with treatment period up to 56 weeks Hypoglycemia Saxenda can lower blood glucose.
• +Added: Six positively adjudicated cases of malignant colorectal neoplasms were reported in 5 Saxenda-treated patients (0.2%, mostly adenocarcinomas) and 1 in a placebo-treated patient (0.1%, neuroendocrine tumor of the rectum).

Removed in this revision

• -Removed: Of these, 1087 Saxenda-treated patients and 497 placebo-treated patients have been exposed in their original randomized groups beyond the primary endpoint for an additional mean duration of 53.0 weeks (median, 56.9 weeks).
• -Removed: T2DM = type 2 diabetes mellitus Hypoglycemia Saxenda can lower blood glucose.
• -Removed: Two positively adjudicated cases of malignant colorectal carcinoma were reported in Saxenda-treated patients (0.1%) and none in placebo-treated patients.

7 entries reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Dosage in Patients With Renal Impairment The recommended maximum dosage of phentermine hydrochloride are 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL min/1.73m 2).
• +Added: Avoid use of phentermine hydrochloride in patients with eGFR less than 15 mL/min/1.73m 2 or end-stage renal disease requiring dialysis.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

Removed in this revision

• -Removed: (See WARNINGS section.)

2 entries reworded without a change of meaning.

Dosage and administration

Removed in this revision

• -Removed: (See PRECAUTIONS section.)

2 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Interference with Laboratory Tests Use of PPIs, including pantoprazole, may increase chromogranin A (CgA) levels which may interfere with investigations for neuroendocrine tumors.
• +Added: To avoid this interference, PPI treatment should be stopped 14 days before CgA measurements.

Approved uses

1 entry 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: Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with TRULICITY.
• +Added: Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists.
• +Added: Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with TRULICITY.

Removed in this revision

• -Removed: Hypersensitivity Reactions Systemic hypersensitivity reactions were observed in patients receiving TRULICITY in clinical trials.

3 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: Postmarketing Experience The following additional adverse reactions have been reported during post-approval use of TRULICITY.
• +Added: Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• +Added: Anaphylactic reactions.

Removed in this revision

• -Removed: Heart Rate Increase and Tachycardia Related Adverse Reactions.

3 entries reworded without a change of meaning.