Omeprazoleside 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 Adults: Most common adverse reactions in adults (incidence ≥2%) are

Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. Pediatric patients (1 to 16 years of age):

Safety profile similar to that in adults, except that respiratory system events and fever were the most frequently reported reactions in pediatric studies. To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience with PRILOSEC Monotherapy 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. The safety data described below reflect exposure to omeprazole magnesium delayed-release capsules in 3096 patients from worldwide clinical trials (465 patients from US studies and 2631 patients from international studies). Indications clinically studied in US trials included duodenal ulcer, resistant ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥2%) from PRILOSEC-treated patients enrolled in these studies included headache (7%), abdominal pain (5%), nausea (4%), diarrhea (4%), vomiting (3%), and flatulence (3%). Additional adverse reactions that were reported with an incidence ≥1% included acid regurgitation (2%), upper respiratory infection (2%), constipation (2%), dizziness (2%), rash (2%), asthenia (1%), back pain (1%), and cough (1%). The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less. The clinical trial safety profile in pediatric patients who received omeprazole magnesium delayed-release capsules was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of the respiratory system were frequently reported in the 1 month to <1 year age group, the 1 to <2 year age group, and the 2 to 16 year age group (42%, 75%, and 19%, respectively). In addition, otitis media was frequently reported in the 1 month to <1 year age group (22%), fever was frequently reported in the 1 to <2 year age group (33% ), and accidental injuries were frequently reported in the 2 to 16 year age group (4%).

6.2 Clinical

Trials Experience with PRILOSEC in Combination Therapy for H. pylori Eradication In clinical trials using either dual therapy with omeprazole magnesium delayed-release capsules and clarithromycin, or triple therapy with omeprazole magnesium delayed-release capsules, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone. Dual Therapy (omeprazole magnesium delayed-release capsules/clarithromycin) Adverse reactions observed in controlled clinical trials using combination therapy with omeprazole magnesium delayed-release capsules and clarithromycin (n = 346) that differed from those previously described for omeprazole magnesium delayed-release capsules alone were taste perversion (15%), tongue discoloration (2%), rhinitis (2%), pharyngitis (1%), and flu-syndrome (1%). (For more information on clarithromycin, refer to the clarithromycin prescribing information, Adverse Reactions section.) Triple Therapy (omeprazole magnesium delayed-release capsules/clarithromycin/amoxicillin) The most frequent adverse reactions observed in clinical trials using combination therapy with omeprazole magnesium delayed-release capsules, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%), taste perversion (10%), and headache (7%). None of these occurred at a higher frequency than that reported by patients taking antimicrobial agents alone. (For more information on clarithromycin or amoxicillin, refer to the respective prescribing information, Adverse Reactions sections.)

6.3 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of omeprazole. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.

Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; systemic lupus erythematosus Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema Endocrine: Gynecomastia Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis, fundic gland polyps. Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin] Infections and Infestations: Clostridium difficile -associated diarrhea Metabolism and Nutritional disorders: Hypomagnesemia, hypocalcemia, hypokalemia [Warnings and Precautions ], hyponatremia, hypoglycemia, weight gain Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo Respiratory: Epistaxis, pharyngeal pain Skin: Severe generalized skin reactions including toxic SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis Special Senses: Tinnitus, taste perversion Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain, erectile dysfunction Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis