Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis or osteoarthritis in controlled NAPROSYN trials are listed below. In general, reactions in patients treated chronically with NAPROSYN were reported 2 to 10 times more frequently than they were in short-term studies in the 962 patients treated for mild to moderate pain or for dysmenorrhea. The most frequent complaints reported related to the GI tract.
A clinical study found GI reactions to be more frequent and more severe in
rheumatoid arthritis patients taking daily doses of 1500 mg naproxen compared
to those taking 750 mg naproxen (see CLINICAL PHARMACOLOGY).
In controlled clinical naproxen trials with about 80 pediatric patients and in well-monitored, open-label naproxen studies with about 400 pediatric patients with juvenile arthritis treated with naproxen, the incidence of rash and prolonged bleeding times were increased, the incidence of GI and central nervous system reactions were about the same, and the incidence of other reactions were lower in pediatric patients than in adults.
In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are:
GI Experiences, including: heartburn*, abdominal pain*, nausea*, constipation*,
diarrhea, dyspepsia, stomatitis
Central Nervous System: headache*, dizziness*, drowsiness*, lightheadedness,
Dermatologic: pruritus (itching)*, skin eruptions*, ecchymoses*, sweating,
Special Senses: tinnitus*, visual disturbances, hearing disturbances
Cardiovascular: edema*, palpitations
General: dyspnea*, thirst
*Incidence of reported reaction between 3% and 9%. Those reactions occurring
in less than 3% of the patients are unmarked.
In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1% to 10% of patients.
GI Experiences, including: flatulence, 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 less than 1% of patients taking naproxen during clinical trials and through postmarketing reports. Those adverse reactions observed through postmarketing reports are italicized.
Body as a Whole: anaphylactoid reactions, angioneurotic edema, menstrual
disorders, pyrexia (chills and fever)
Cardiovascular: congestive heart failure, vasculitis, hypertension,
GI: GI bleeding and/or perforation, hematemesis, pancreatitis,
vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative
colitis, Crohn's disease), nonpeptic GI ulceration, ulcerative stomatitis, esophagitis,
Hepatobiliary: jaundice, abnormal liver function tests, hepatitis
(some cases have been fatal)
Hemic and Lymphatic: eosinophilia, leucopenia, melena, thrombocytopenia,
agranulocytosis, granulocytopenia, hemolytic anemia, aplastic anemia
Metabolic and Nutritional: hyperglycemia, hypoglycemia
Nervous System: inability to concentrate, depression, dream abnormalities,
insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction,
Respiratory: eosinophilic pneumonitis, asthma
Dermatologic: alopecia, urticaria, skin rashes, 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
In patients taking NSAIDs, the following adverse experiences have also been
reported in less than 1% of patients:
Body as a Whole: fever, infection, sepsis, anaphylactic reactions, appetite
Cardiovascular: hypertension, tachycardia, syncope, arrhythmia, hypotension,
GI: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, glossitis,
Hepatobiliary: hepatitis, liver failure
Hemic and Lymphatic:rectal bleeding, lymphadenopathy, pancytopenia
Metabolic and Nutritional: weight changes
Nervous System: anxiety, asthenia, confusion, nervousness, paresthesia,
somnolence, tremors, convulsions, coma, hallucinations
Respiratory: asthma, respiratory depression, pneumonia
Dermatologic: exfoliative dermatitis
Special Senses: blurred vision, conjunctivitis
Urogenital: cystitis, dysuria, oliguria/polyuria, proteinuria
Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. The adverse reaction profiles for PREVACID Delayed-Release Capsules and PREVACID for Delayed-Release Oral Suspension are similar. In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials.
The following adverse events were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients in Table 4.
Table 4: Incidence of Possibly or Probably Treatment-Related
Adverse Events in Short-Term, Placebo-Controlled PREVACID Studies
|Body System/Adverse Event
|Body as a Whole
| Abdominal Pain
Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 mg and 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9%, 1.4%, 4.2%, and 7.4%, respectively).
The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.
In the risk reduction study of PREVACID for NSAID-associated gastric ulcers,
the incidence of diarrhea for patients treated with PREVACID, misoprostol, and
placebo was 5%, 22%, and 3%, respectively.
Another study for the same indication, where patients took either a COX-2 inhibitor
or lansoprazole and naproxen, demonstrated that the safety profile was similar
to the prior study. Additional events from this study not previously observed
in other clinical trials with PREVACID included contusion, duodenitis, epigastric
discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness,
impaired gastric emptying, metaplasia, and renal impairment.
Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below:
Body as a Whole – abdomen enlarged, allergic reaction, asthenia,
back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills,
edema, fever, flu syndrome, halitosis, infection (not otherwise specified),
malaise, neck pain, neck rigidity, pain, pelvic pain; Cardiovascular System
- angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction,
hypertension/hypotension, migraine, myocardial infarction, palpitations, shock
(circulatory failure), syncope, tachycardia, vasodilation; Digestive System
– abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry
mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal
ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic
gland polyps, gastritis, gastroenteritis, GI anomaly, GI disorder, GI hemorrhage,
glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation,
melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea,
gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis,
tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis;
Endocrine System - diabetes mellitus, goiter, hypothyroidism;
Hemic and Lymphatic System - anemia, hemolysis, lymphadenopathy;
Metabolic and Nutritional Disorders - avitaminosis, gout, dehydration,
hyperglycemia /hypoglycemia, peripheral edema, weight gain/loss; Musculoskeletal
System - arthralgia, arthritis, bone disorder, joint disorder, leg cramps,
musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis; Nervous
System - abnormal dreams, agitation, amnesia, anxiety, apathy, confusion,
convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional
lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia,
hypesthesia, insomnia, libido decreased /increased, nervousness, neurosis, paresthesia,
sleep disorder, somnolence, thinking abnormality, tremor, vertigo; Respiratory
System - asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis,
hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia,
respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis,
stridor; Skin and Appendages - acne, alopecia, contact dermatitis,
dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder,
pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria; Special
Senses - abnormal vision, amblyopia, blepharitis, blurred vision, cataract,
conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste
perversion, tinnitus, visual field defect; Urogenital System -
abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea,
dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea,
menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder,
urethral pain, urinary frequency, urinary retention, urinary tract infection,
urinary urgency, urination impaired, vaginitis.
Additional adverse experiences have been reported since PREVACID has been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID has not been established. Because these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below by COSTART body system.
Body as a Whole - anaphylactic/anaphylactoid reactions; Digestive
System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic
System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia,
neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic
purpura; Musculoskeletal System – myositis; Skin and Appendages
– severe dermatologic reactions including erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis (some fatal); Special Senses
- speech disorder; Urogenital System – interstitial nephritis,
The following changes in laboratory parameters in patients who received PREVACID were reported as adverse events:
Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported.
In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4 of 978) and 0.4% (11 of 2677) patients, who received placebo and PREVACID, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received PREVACID reported jaundice at any time during the study.