ADVERSE REACTIONS
Safety Experience with Intravenous Pantoprazole
Intravenous pantoprazole has been studied in clinical trials in several populations including patients with GERD and a history of erosive esophagitis, patients with Zollinger-Ellison Syndrome, patients involved in clinical trials for other disorders which may respond to proton pump inhibitor therapy, and healthy subjects. Adverse experiences occurring in >1% of patients treated with intravenous pantoprazole (n=836) in domestic or international clinical trials are shown below by body system. In most instances, the relationship to pantoprazole was unclear.
BODY AS A WHOLE: abdominal pain, headache, injection site reaction (including thrombophlebitis and abscess).
DIGESTIVE SYSTEM: constipation, dyspepsia, nausea, diarrhea.
NERVOUS SYSTEM: insomnia, dizziness.
RESPIRATORY SYSTEM: rhinitis.
Head-to-head comparative studies between PROTONIX I.V. for Injection and oral PROTONIX, other proton pump inhibitors (oral or I.V.), or H2 receptor antagonists (oral or I.V.) have been limited. The available information does not provide sufficient evidence to distinguish the safety profile of these regimens.
Safety Experience with Oral Pantoprazole
In short-term clinical trials in patients with erosive esophagitis associated with GERD treated with oral pantoprazole, the following adverse events, regardless of causality, occurred at a rate of ≥1%.
BODY AS A WHOLE: headache, asthenia, back pain, chest pain, neck pain, flu syndrome, infection, pain.
CARDIOVASCULAR SYSTEM: migraine.
DIGESTIVE SYSTEM: diarrhea, flatulence, abdominal pain, eructation, constipation, dyspepsia, gastroenteritis, gastrointestinal disorder, nausea, rectal disorder, vomiting.
HEPATO-BILIARY SYSTEM: liver function tests abnormal, SGPT increased.
METABOLIC AND NUTRITIONAL: hyperglycemia, hyperlipemia.
MUSCULOSKELETAL SYSTEM: arthralgia.
NERVOUS SYSTEM: insomnia, anxiety, dizziness, hypertonia.
RESPIRATORY SYSTEM: bronchitis, cough increased, dyspnea, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.
SKIN AND APPENDAGES: rash.
UROGENITAL SYSTEM: urinary frequency, and urinary tract infection.
Additional adverse experiences occurring in <1% of patients with erosive esophagitis associated with GERD receiving oral pantoprazole based on pooled results from either short-term domestic or international trials are shown below within each 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.
CARDIOVASCULAR SYSTEM: abnormal electrocardiogram, angina pectoris, arrhythmia, cardiovascular disorder, chest pain substernal, congestive heart failure, hemorrhage, hypertension, hypotension, 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, 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, pain, 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 addition, the following adverse experiences occurred at a rate of <1% in long-term clinical trials in patients treated with oral pantoprazole: atrial fibrillation/flutter, myocardial infarction, neuropathy, photosensitivity reaction. In most instances, the relationship to pantoprazole was unclear.
Postmarketing Reports
The postmarketing safety profile of intravenous pantoprazole is not substantially different from that of oral pantoprazole (described below).
There have been spontaneous reports of adverse events with postmarketing use of intravenous or oral 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 U.S. clinical trials of patients with GERD and a history of erosive esophagitis and international clinical trials of patients with erosive esophagitis associated with GERD, the overall percentages of transaminase elevations did not increase during treatment with intravenous pantoprazole. For other laboratory parameters, there were no clinically important changes identified.
In two U.S. controlled trials of oral pantoprazole in patients with erosive esophagitis associated with GERD, 0.4% of the patients on 40 mg oral pantoprazole experienced SGPT elevations of greater than three times the upper limit of normal at the final treatment visit. Except in those patients where there was a clear alternative explanation for a laboratory value change, such as intercurrent illness, the elevations tended to be mild and sporadic. The following changes in laboratory parameters were reported as adverse events: creatinine increased, hypercholesterolemia, and hyperuricemia.
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