Esomeprazoleside effects

The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis Clostridium difficile-Associated Diarrhea Bone Fracture Severe Cutaneous Adverse Reactions Cutaneous and Systemic Lupus Erythematosus Cyanocobalamin (Vitamin B-12) Deficiency Hypomagnesemia and Mineral Metabolism Fundic Gland Polyps Most common adverse reactions: Adults (≥ 18 years) (> 1%) are: headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth. Pediatrics (1 to 17 years) (≥ 2%) are: headache, diarrhea, abdominal pain, nausea, and somnolence. Pediatrics (1 month to less than 1 year) (> 1%) are: abdominal pain, regurgitation, tachypnea, and increased ALT. To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

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 practice. Adults The safety of esomeprazole magnesium delayed-release capsules was evaluated in over 15,000 patients (aged 18 to 84 years) in clinical trials worldwide including over 8,500 patients in the United States and over 6,500 patients in Europe and Canada. Over 2,900 patients were treated in long-term studies for up to 6 to 12 months. The safety in the treatment of healing of EE in adults was assessed in four randomized comparative clinical trials, which included 1,240 patients who received esomeprazole magnesium 20 mg once daily, 2,434 patients on esomeprazole magnesium 40 mg once daily, and 3,008 patients on omeprazole 20 mg once daily. The most frequently occurring adverse reactions (at least 1%) in all three groups were headache (5.5%, 5%, and 3.8%, respectively) and diarrhea (no difference among the three groups). Nausea, flatulence, abdominal pain, constipation, and dry mouth occurred at similar rates among patients taking esomeprazole magnesium or omeprazole. Less common adverse reactions with an incidence of less than 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, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors; Cardiovascular flushing, hypertension, tachycardia; Endocrine goiter; Gastrointestinal bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, 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, dizziness, 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, taste perversion; 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 magnesium, were reported in 1% or less 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, gastritis, hernia, benign polyps or nodules, Barrett's esophagus, and mucosal discoloration. The incidence of adverse reactions during 6 month trials for the maintenance of healing of EE with esomeprazole magnesium 20 mg once daily was similar to placebo. There were no differences in types of adverse reactions seen during maintenance treatment up to 12 months compared to short-term treatment. Two placebo-controlled studies were conducted in 710 adult patients for the treatment of symptomatic GERD. The most common adverse reactions that were reported were: diarrhea (4%), headache (4%), and abdominal pain (4%). Combination Treatment with Esomeprazole Magnesium, Amoxicillin and Clarithromycin In clinical trials of H. pylori eradication of to reduce duodenal ulcer recurrence, no additional adverse reactions specific to the combination of esomeprazole magnesium delayed-release capsules, amoxicillin and clarithromycin were observed and were similar to those observed with esomeprazole magnesium, amoxicillin, or clarithromycin alone. The most frequently reported adverse reactions for patients who received esomeprazole magnesium, amoxicillin and clarithromycin for 10 days were diarrhea (9%), taste perversion (4%), and abdominal pain (4%). No adverse reactions were observed at higher rates with esomeprazole magnesium, amoxicillin and clarithromycin than were observed with esomeprazole magnesium alone. In clinical trials using of esomeprazole magnesium, amoxicillin and clarithromycin, no additional increased laboratory abnormalities particular to these drug combinations were observed. For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to Adverse Reactions section of the respective prescribing information. Pediatrics 1 Year to 17 Years of Age The safety of esomeprazole magnesium for delayed-release oral suspension was evaluated in 316 pediatric and adolescent patients aged 1 year to 17 years in four clinical trials for the treatment of symptomatic GERD. In 109 pediatric patients aged 1 year to 11 years, the most frequently reported (at least 1%) treatment-related adverse reactions in these patients were diarrhea (3%), headache (2%) and somnolence (2%). In 149 pediatric patients aged 12 years to 17 years the most frequently reported adverse reactions (at least 2%) were headache (8%), abdominal pain (3%), diarrhea (2%), and nausea (2%). 1 Month to Less Than 1 Year of Age The safety of esomeprazole magnesium was evaluated in 167 infants from 1 month to less than 1 year of age with GERD in three clinical trials. In a study that included 43 pediatric patients, the most frequently reported adverse reactions (at least 5%) with esomeprazole magnesium were irritability and vomiting. In a study that included 98 pediatric patients, administered esomeprazole magnesium for up to 6 weeks (including 39 patients randomized to the withdrawal phase), reported adverse reactions were: abdominal pain (1%), regurgitation (1%), tachypnea (1%), and increased ALT (1%).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of esomeprazole. 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 reports are listed below by body system: Blood and Lymphatic agranulocytosis, pancytopenia; Eye blurred vision; Gastrointestinal pancreatitis; stomatitis; microscopic colitis; fundic gland polyps; Hepatobiliary hepatic failure, hepatitis with or without jaundice; Immune System anaphylactic reaction/shock; systemic lupus erythematosus; Infections and Infestations GI candidiasis; Clostridium difficile- associated diarrhea; Metabolism and nutritional disorders hypomagnesemia (may lead to hypocalcemia and/or hypokalemia ); Musculoskeletal and Connective Tissue muscular weakness, myalgia, bone fracture; Nervous System hepatic encephalopathy, taste disturbance; Psychiatric aggression, agitation, depression, hallucination; Renal and Urinary interstitial nephritis; Reproductive System and Breast Gynecomastia, erectile dysfunction; Respiratory, Thoracic, and Mediastinal bronchospasm; Skin and Subcutaneous Tissue alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), cutaneous lupus erythematosus. Adverse reactions associated with omeprazole may also be expected to occur with esomeprazole. See the full prescribing information for omeprazole for complete safety information.