adverse reactions
ADVERSE REACTIONS Worldwide, more than 11,100 patients have been treated with pantoprazole in clinical trials involving various dosages and duration of treatment. In general, pantoprazole has been well tolerated in both short-term and long-term trials. In two U.S. controlled clinical trials involving pantoprazole sodium 10, 20, or 40 mg doses for up to 8 weeks, there were no dose-related effects on the incidence of adverse events. The following adverse events considered by investigators to be possibly, probably, or definitely related to drug occurred in 1% or more in the individual studies of GERD patients on therapy with pantoprazole sodium. Most Frequent Adverse Events Reported as Drug Related in Short-term Domestic Trials % IncidenceStudy 300-USStudy 301-USStudy EventPantoprazole sodium (n = 521)Placebo (n = 82)Pantoprazole sodium (n = 161)Nizatidine (n = 82)Headache Diarrhea Flatulence Abdominal pain Rash Eructation Insomnia Hyperglycemia6 4 2 1 <1 1 <1 16 1 2 2 0 1 2 09 6 4 4 2 0 1 <113 6 0 4 0 0 1 0Note: Only adverse events with an incidence greater than or equal to the comparators are shown. In international short-term, double-blind or open-label clinical trials involving 20 mg to 80 mg per day, the following adverse events were reported to occur in 1% or more of 2805 GERD patients receiving pantoprazole for up to 8 weeks. Adverse Events in GERD Patients in Short-term International Trials % IncidenceStudy EventPantoprazole Total (N = 2805)Ranitidine 300 mg (N = 594)Omeprazole 20 mg (N = 474)Famotidine 40 mg (N = 239)Headache Diarrhea Abdominal pain2 2 13 2 12 2 <11 <1 <1In two U.S. controlled clinical trials involving pantoprazole sodium 10, 20, or 40 mg doses for up to 12 months, the following adverse events considered by investigators to be possibly, probably, or definitely related to drug occurred in 1% or more of GERD patients on long-term therapy. Most Frequent Adverse Events Reported as Drug Related in Long-term Domestic Trials % IncidenceStudy EventPantoprazole sodium (n = 536)Ranitidine (n = 185)Headache Abdominal pain Liver function tests abnormal Nausea Vomiting5 3 2 2 22 1 <1 2 2Note: Only adverse events with an incidence greater than or equal to the comparators are shown.In addition, in these short- and long-term domestic and international trials, the following treatment-emergent events, regardless of causality, occurred at a rate of1% in pantoprazole-treated patients: anxiety, arthralgia, asthenia, back pain, bronchitis, chest pain, constipation, cough increased, dizziness, dyspepsia, dyspnea, flu syndrome, gastroenteritis, gastrointestinal disorder, hyperlipemia, hypertonia, infection, liver function tests abnormal, migraine, nausea, neck pain, pain, pharyngitis, rectal disorder, rhinitis, SGPT increased, sinusitis, upper respiratory tract infection, urinary frequency, urinary tract infection, and vomiting. Additional treatment-emergent adverse experiences occurring in < 1% of pantoprazole-treated patients from these trials are listed below by body system. In most instances the relationship to pantoprazole was unclear. BODY AS A WHOLE: abscess, allergic reaction, chills, cyst, face edema, fever, generalized edema, heat stroke, hernia, laboratory test abnormal, malaise, moniliasis, neoplasm, non-specified drug reaction, photosensitivity reaction. CARDIOVASCULAR SYSTEM: abnormal electrocardiogram, angina pectoris, arrhythmia, atrial fibrillation/flutter, cardiovascular disorder, chest pain substernal, congestive heart failure, hemorrhage, hypertension, hypotension, myocardial infarction, myocardial ischemia, palpitation, retinal vascular disorder, syncope, tachycardia, thrombophlebitis, thrombosis, vasodilatation. DIGESTIVE SYSTEM: anorexia, aphthous stomatitis, cardiospasm, colitis, dry mouth, duodenitis, dysphagia, enteritis, esophageal hemorrhage, esophagitis, gastrointestinal carcinoma, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, glossitis, halitosis, hematemesis, increased appetite, melena, mouth ulceration, oral moniliasis, periodontal abscess, periodontitis, rectal hemorrhage, stomach ulcer, stomatitis, stools abnormal, tongue discoloration, ulcerative colitis. ENDOCRINE SYSTEM: diabetes mellitus, glycosuria, goiter. HEPATO-BILIARY SYSTEM: biliary pain, hyperbilirubinemia, cholecystitis, cholelithiasis, cholestatic jaundice, hepatitis, alkaline phosphatase increased, gamma glutamyl transpeptidase increased, SGOT increased. HEMIC AND LYMPHATIC SYSTEM: anemia, ecchymosis, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, leukopenia, thrombocytopenia. METABOLIC AND NUTRITIONAL: dehydration, edema, gout, peripheral edema, thirst, weight gain, weight loss. MUSCULOSKELETAL SYSTEM: arthritis, arthrosis, bone disorder, bone pain, bursitis, joint disorder, leg cramps, neck rigidity, myalgia, tenosynovitis. NERVOUS SYSTEM: abnormal dreams, confusion, convulsion, depression, dry mouth, dysarthria, emotional lability, hallucinations, hyperkinesia, hypesthesia, libido decreased, nervousness, neuralgia, neuritis, neuropathy, paresthesia, reflexes decreased, sleep disorder, somnolence, thinking abnormal, tremor, vertigo. RESPIRATORY SYSTEM: asthma, epistaxis, hiccup, laryngitis, lung disorder, pneumonia, voice alteration. SKIN AND APPENDAGES: acne, alopecia, contact dermatitis, dry skin, eczema, fungal dermatitis, hemorrhage, herpes simplex, herpes zoster, lichenoid dermatitis, maculopapular rash, pruritus, skin disorder, skin ulcer, sweating, urticaria. SPECIAL SENSES: abnormal vision, amblyopia, cataract specified, deafness, diplopia, ear pain, extraocular palsy, glaucoma, otitis externa, taste perversion, tinnitus. UROGENITAL SYSTEM: albuminuria, balanitis, breast pain, cystitis, dysmenorrhea, dysuria, epididymitis, hematuria, impotence, kidney calculus, kidney pain, nocturia, prostatic disorder, pyelonephritis, scrotal edema, urethral pain, urethritis, urinary tract disorder, urination impaired, vaginitis. In an open-label US clinical trial conducted in 35 patients with pathological hypersecretory conditions treated with pantoprazole sodium for up to 27 months, the adverse events reported were consistent with the safety profile of the drug in other populations. Postmarketing Reports There have been spontaneous reports of adverse events with the postmarketing use of pantoprazole. These reports include the following: BODY AS A WHOLE: anaphylaxis (including anaphylactic shock), angioedema (Quincke's edema). DIGESTIVE SYSTEM: increased salivation, nausea, pancreatitis. HEMIC AND LYMPHATIC SYSTEM: pancytopenia. HEPATO-BILIARY SYSTEM: hepatocellular damage leading to jaundice and hepatic failure. MUSCULOSKELETAL SYSTEM: elevated CPK (creatine phosphokinase), rhabdomyolysis. NERVOUS SYSTEM: confusion, hypokinesia, speech disorder, vertigo. SKIN AND APPENDAGES: severe dermatologic reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal). SPECIAL SENSES: anterior ischemic optic neuropathy, blurred vision, tinnitus. UROGENITAL SYSTEM: interstitial nephritis. Laboratory Values In two U.S. controlled, short-term trials in patients with erosive esophagitis associated with GERD, 0.4% of the patients on pantoprazole sodium 40 mg experienced SGPT elevations of greater than three times the upper limit of normal at the final treatment visit. In two U.S. controlled, long-term trials in patients with erosive esophagitis associated with GERD, none of 178 patients (0%) on pantoprazole sodium 40 mg and two of 181 patients (1.1%) on pantoprazole sodium 20 mg experienced significant transaminase elevations at 12 months (or earlier if a patient discontinued prematurely). Significant elevations of SGOT or SGPT were defined as values at least three times the upper limit of normal that were non-sporadic and had no clear alternative explanation. The following changes in laboratory parameters were reported as adverse events: creatinine increased, hypercholesterolemia, and hyperuricemia.