Safety

Vimovo (naproxen/esomeprazole magnesium) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

May 2016

Summary View

BOXED WARNING

  • This section has had an extensive update, please refer to label.

CONTRAINDICATIONS

  • This section has had an extensive update, please refer to label.

WARNINGS AND PRECAUTIONS

The following sections all include extensive updates, please refer to label:

  • Cardiovascular Thrombotic Events
    • Status Post Coronary Artery Bypass Graft (CABG) Surgery
    • Post-MI Patients
       
  • Gastrointestinal Bleeding, Ulceration, and Perforation
    • Risk Factors for GI Bleeding, Ulceration, and Perforation
    • Strategies to Minimize the GI Risks in NSAID-treated patients
       
  • Hepatotoxicity
  • Heart Failure and Edema
  • Renal Toxicity and Hyperkalemia
  • Anaphylactic Reactions
  • Exacerbation of Asthma Related to Aspirin Sensitivity
  • Serious Skin Reactions
  • Premature Closure of Fetal Ductus Arteriosis
  • Hematologic Toxicity
  • Masking of Inflammation and Fever
  • Laboratory Monitoring
  • Concurrent Gastric Malignancy
  • Atrophic Gastritis
  • Interactions with Diagnostic Investigations for Neuroendocrine Tumors

ADVERSE REACTIONS

The following sections all include extensive updates, please refer to label:

The following adverse reactions are discussed in greater detail in other sections of the labeling

  • Clinical Trials Experience
    • Clinical Trials Experience with {product name}
  • Post Marketing Experience

DRUG INTERACTIONS

  • There has been updated information added, in table formation, please refer to label.

USE IN SPECIFIC POPULATIONS

  • Label has been updated to reflect PLLR conversion

PATIENT INFORMATION

  • This section has been updated extensively, please refer to label.

MEDICATION GUIDE

  • This section has been updated extensively, please refer to label.

 

June 2015

Summary View

WARNINGS AND PRECAUTIONS

  • Advanced Renal Disease: …patients should be adequately hydrated…

ADVERSE REACTIONS

Clinical Trials Experience with Naproxen and Other NSAIDs

In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are:

  • Gastrointestinal: heartburn, nausea, dyspepsia, stomatitis
  • Central Nervous System: drowsiness, lightheadedness, vertigo
  • Dermatologic: pruritus, skin eruptions, ecchymoses, sweating, purpura
  • Special Senses: tinnitus, visual disturbances, hearing disturbances
  • Cardiovascular: palpitations
  • General: dyspnea, thirst

In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1% to 10% of patients.

  • Gastrointestinal: gross bleeding/perforation, GI ulcers (gastric/duodenal), vomiting
  • General: abnormal renal function, anemia, elevated liver enzymes, increased bleeding time, rashes

The following are additional adverse experiences reported in <1% of patients taking naproxen during clinical trials

  • Gastrointestinal: pancreatitis
  • Hepatobiliary: jaundice
  • Hemic and Lymphatic: melena, thrombocytopenia, agranulocytosis
  • Nervous System: inability to concentrate
  • Dermatologic: skin rashes


In patients taking NSAIDs, the following adverse experiences have also been reported in <1% of patients

  • Body as a Whole: fever, infection, sepsis, anaphylactic reactions, appetite changes, death
  • Cardiovascular: hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction
  • Gastrointestinal: dry mouth, glossitis, eructation
  • Hepatobilitary: hepatitis, liver failure
  • Hemic and Lymphatic: rectal bleeding, lymphadenopathy, pancytopenia
  • Metabolic and Nutritional: weight changes
  • Nervous System: anxiety, asthenia, confusion, nervousness, paresthesia, somnolence, tremor, coma, hallucinations
  • Respiratory: asthma, respiratory depression, pneumonia
  • Dermatologic: exfoliative dermatitis
  • Special Senses: blurred vision, conjunctivitis
  • Urogenital: cystitis, dysuria, oliguria/polyuria, proteinuria

Clinical Trials Experience with Esomeprazole Magnesium

Additional adverse reactions that were reported as possibly or probably related to NEXIUM with an incidence < 1% are listed below by body system:
 

  • Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, , malaise, pain, rigors
  • Cardiovascular: flushing, hypertension, tachycardia
  • Endocrine: goiter
  • Gastrointestinal:, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting
  • Hearing: earache, tinnitus
  • Hematologic: anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia
  • Hepatic: bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased
  • Metabolic/Nutritional: glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease
  • Musculoskeletal: arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica
  • Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect
  • Reproductive: dysmenorrhea, menstrual disorder, vaginitis
  • Respiratory: asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis
  • Skin and Appendages: acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria
  • Special Senses: otitis media, parosmia, taste loss
  • Urogenital: abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria
  • Visual: conjunctivitis, vision abnormal


The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to esomeprazole, were reported in ≤ 1% of patients: increased creatinine, uric acid, total bilirubin, alkaline phosphatase, ALT, AST, hemoglobin, white blood cell count, platelets, serum gastrin, potassium, sodium, thyroxine and thyroid stimulating hormone. Decreases were seen in hemoglobin, white blood cell count, platelets, potassium, sodium, and thyroxine.

Endoscopic findings that were reported as adverse reactions include: duodenitis, esophagitis, esophageal stricture, esophageal ulceration, esophageal varices, gastric ulcer, hernia, benign polyps or nodules, Barrett’s esophagus, and mucosal discoloration.

Postmarketing Experience

Vimovo
 

  • Body as a Whole: gait disturbance
  • Gastrointestinal: abdominal distension, abdominal pain, gastroesophageal reflux, Hematochezia
  • Injury, Poisoning and Procedural Complications: contusion, fall
  • Musculoskeletal and Connective Tissue: joint swelling, muscle spasms
  • Urogenital: renal tubular necrosis

Naproxen

  • Body as aWhole: angioneurotic edema, menstrual disorders
  • Cardiovascular: congestive heart failure, vasculitis, pulmonary edema
  • Gastrointestinal: inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, and obstruction of the upper or lower gastrointestinal tract, esophagitis, stomatitis, hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
  • Hepatobiliary: hepatitis (some cases have been fatal)
  • Hemic and Lymphatic: eosinophilia, hemolytic anemia, aplastic anemia
  • Metabolic and Nutritional: hyperglycemia, hypoglycemia
  • Nervous System: depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions
  • Respiratory: eosinophilic pneumonitis
  • Dermatologic: alopecia, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa. If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.
  • Special Senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema
  • Urogenital: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine
  • Reproduction (female): infertility
  • Esomeprazole Magnesium
  • Blood and Lymphatic: agranulocytosis
  • Eye: blurred vision
  • Gastrointestinal: pancreatitis, microscopic colitis
  • Hepatobiliary: hepatic failure, hepatitis with or without jaundice
  • Immune System: anaphylactic reaction/shock
  • Infections and Infestations: GI candidiasis, Clostridium difficile associated diarrhea
  • Metabolism and Nutritional Disorders: hypomagnesemia, with or without hypocalcemia and/or hypokalemia
  • Musculoskeletal and Connective Tissue: muscular weakness, myalgia, bone fracture
  • Nervous System: hepatic encephalopathy
  • Psychiatric: aggression, agitation, hallucination
  • Renal and Urinary: interstitial nephritis
  • Reproductive System and Breast: gynecomastia
  • Respiratory, Thoracic, and Mediastinal: bronchospasm
  • Skin and Subcutaneous Tissue: alopecia, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal)

 

December 2014

Summary View

WARNINGS AND PRECAUTIONS

Acute Interstitial Nephritis

*Section Added

Cyanocobalamin (vitamin B12) Deficiency

*Section added

DRUG INTERACTIONS

*Addition of information regarding concomitant dosing of mycophenolate mofetil with PPIs resulting in reduced systemic exposure of mycophenolate mofetil
 

 

March 2014

Summary View

WARNINGS AND PRECAUTIONS

Renal Effects
  • Patients at greatest risk of this reaction are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics, ACE inhibitors, or angiotensin II receptor antagonists and the elderly.
Laboratory Tests
  • Healthcare providers should temporarily stop esomeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. 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

 

January 2012

Summary View

5 WARNINGS AND PRECAUTIONS

5.21 Concomitant use of VIMOVO with Methotrexate
  • Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate...

6 ADVERSE REACTIONS

6.2 Postmarketing Experience
  • esomeprazole - microsopic colitis....added

7 DRUG INTERACTIONS

7.8 Methotrexate
  • NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. NSAIDs have been reported.....
7.14 Interactions Related to Absorption
  • ...Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazle, iron salts and erlotinib can decrease...

MEDICATION GUIDE

Tell your healthcare provider about all the medicines you take.....

Especially tell your healthcare provider if you take:

  • Erlotinib (or another anticancer drug from the same class)

 

November 2011

Summary View

WARNINGS AND PRECAUTIONS

Bone Fracture
  • Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer).
  • Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines.
  • Vimovo (a combination PPI/NSAID) is approved for use twice a day and does not allow for administration of a lower daily dose of the PPI.

ADVERSE REACTIONS

Postmarketing Experience
  • bone fracture 

 

June 2011

Summary View

WARNINGS AND PRECAUTIONS

  • information regarding severe hepatic impairment, interactions with diagnostic investigations for neuroendocrine tumors, and concomitant use with St. John’s Wort or rifampin

DRUG INTERACTIONS

  • information regarding interactions with diagnostic investigations for neuroendocrine tumors, and concomitant use with cyclosporine, tacrolimus, anticoagulants, digoxin, and St. John’s Wort or rifampin

SPECIAL POPULATIONS

  • information regarding severe hepatic impairment

 

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