The following serious adverse reactions are described below and elsewhere in labeling: Acute Interstitial Nephritis [see Warnings and Precautions (5.2)] Clostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.3)] Bone Fracture [see Warnings and Precautions (5.4)] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)] Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6)] Hypomagnesemia [see Warnings and Precautions (5.7)] The most frequently occurring adverse reactions are as follows: For adult use (>2%) are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia.
(6) For pediatric use (>4%) are URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. (6) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc at 1-269-544-2299 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another proton pump inhibitor, and 82 patients on placebo.
The most frequently occurring adverse reactions are listed in Table 3. Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of > 2% Pantoprazole Comparators Placebo (n=1473) (n=345) (n=82) % % % Headache 12.2 12.8
1.2 Additional adverse reactions that were reported for pantoprazole in clinical trials with a frequency of ≤ 2% are listed below by body system: Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia, thrombocytopenia Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated Musculoskeletal: myalgia Nervous: depression, vertigo Skin and Appendages: urticaria, rash, pruritus Special Senses: blurred vision Pediatric Patients Safety of pantoprazole in the treatment of Erosive Esophagitis (EE) associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials.
Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain.
For safety information in patients less than 1 year of age see Use in Specific Populations (8.4) . Additional adverse reactions that were reported for pantoprazole in pediatric patients in clinical trials with a frequency of ≤ 4% are listed below by body system: Body as a Whole: allergic reaction, facial edema Gastrointestinal: constipation, flatulence, nausea Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase) Musculoskeletal: arthralgia, myalgia Nervous: dizziness, vertigo Skin and Appendages: urticaria The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.
Zollinger-Ellison Syndrome In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.
6.2Postmarketing Experience
The following adverse reactions have been identified during postapproval use of pantoprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are listed below by body system: General Disorders and Administration Conditions: asthenia, fatigue, malaise Hematologic : pancytopenia, agranulocytosis Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus Infections and Infestations : Clostridium difficile associated diarrhea Investigations: weight changes Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia Musculoskeletal Disorders: rhabdomyolysis, bone fracture Nervous : ageusia, dysgeusia Psychiatric Disorders: hallucination, confusion, insomnia, somnolence Renal and Urinary Disorders: interstitial nephritis Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal), and angioedema (Quincke's edema) and cutaneous lupus erythematosus
