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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 clinical practice.

In the U.S. clinical trial population of 465 patients, the adverse reactions summarized in Table 2 were reported to occur in 1% or more of patients on therapy with omeprazole. Numbers in parentheses indicate percentages of the adverse reactions considered by investigators as possibly, probably or definitely related to the drug.

Table 2: Adverse Reactions Occurring In 1% or More of Patients on Omeprazole Therapy

  Omeprazole
(n = 465)
Placebo
(n = 64)
Ranitidine
(n = 195)
Headache 6.9 (2.4) 6.3 7.7 (2.6)
Diarrhea 3.0 (1.9) 3.1 (1.6) 2.1 (0.5)
Abdominal Pain 2.4 (0.4) 3.1 2.1
Nausea 2.2 (0.9) 3.1 4.1 (0.5)
URI 1.9 1.6 2.6
Dizziness 1.5 (0.6) 0.0 2.6 (1.0)
Vomiting 1.5 (0.4) 4.7 1.5 (0.5)
Rash 1.5 (1.1) 0.0 0.0
Constipation 1.1 (0.9) 0.0 0.0
Cough 1.1 0.0 1.5
Asthenia 1.1 (0.2) 1.6 (1.6) 1.5 (1.0)
Back Pain 1.1 0.0 0.5

Table 3 summarizes the adverse reactions that occurred in 1% or more of omeprazole-treated patients from international double-blind, and open-label clinical trials in which 2,631 patients and subjects received omeprazole.

Table 3: Incidence of Adverse Reactions ≥ 1% Causal Relationship not Assessed

  Omeprazole
(n = 2631)
Placebo
(n = 120)
Body as a Whole, site unspecified
  Abdominal pain 5.2 3.3
  Asthenia 1.3 0.8
Digestive System
  Constipation 1.5 0.8
  Diarrhea 3.7 2.5
  Flatulence 2.7 5.8
  Nausea 4.0 6.7
  Vomiting 3.2 10.0
  Acid regurgitation 1.9 3.3
Nervous System/Psychiatric
  Headache 2.9 2.5

A controlled clinical trial was conducted in 359 critically ill patients, comparing ZEGERID 40 mg/1680 mg suspension once daily to I.V. cimetidine 1200 mg/day for up to 14 days. The incidence and total number of AEs experienced by ≥ 3% of patients in either group are presented in Table 4 by body system and preferred term.

Table 4: Number (%) of Critically Ill Patients with Frequently Occurring ( ≥ 3%) Adverse Events by Body System and Preferred Term

MedDRA
Body System Preferred Term
ZEGERID®
(N=178)
Cimetidine
(N=181)
All AEs n (%) All AEs n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
  Anemia NOS 14 (7.9) 14 (7.7)
  Anemia NOS Aggravated 4 (2.2) 7(3.9)
  Thrombocytopenia 18 (10.1) 11 (6.1)
CARDIAC DISORDERS
  Atrial Fibrillation 11 (6.2) 7(3.9)
  Bradycardia NOS 7(3.9) 5 (2.8)
  Supraventricular Tachycardia 6 (3.4) 2(1.1)
  Tachycardia NOS 6 (3.4) 6 (3.3)
  Ventricular Tachycardia 8 (4.5) 6 (3.3)
GASTROINTESTINAL DISORDERS *
  Constipation 8 (4.5) 8 (4.4)
  Diarrhea NOS 7(3.9) 15 (8.3)
  Gastric Hypomotility 3 (1.7) 6 (3.3)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
  Hyperpyrexia 8 (4.5) 3 (1.7)
  Edema NOS 5 (2.8) 11 (6.1)
  Pyrexia 36 (20.2) 29 (16.0)
INFECTIONS AND INFESTATIONS
  Candidal Infection NOS  3 (1.7) 7 (3.9)
  Oral Candidiasis 7 (3.9) 1 (0.6)
  Sepsis NOS 9 (5.1) 9 (5.0)
  Urinary Tract Infection NOS 4 (2.2) 6 (3.3)
INVESTIGATIONS
  Liver Function Tests NOS Abnormal 3 (1.7) 6 (3.3)
METABOLISM AND NUTRITION DISORDERS
  Fluid Overload 9 (5.1) 14 (7.7)
  Hyperglycaemia NOS 19 (10.7) 21 (11.6)
  Hyperkalaemia 4 (2.2) 6 (3.3)
  Hypernatraemia 3 (1.7) 9 (5.0)
  Hypocalcaemia 11 (6.2) 10 (5.5)
  Hypoglycaemia NOS 6 (3.4) 8 (4.4)
  Hypokalaemia 22 (12.4) 24 (13.3)
  Hypomagnesaemia 18 (10.1) 18 (9.9)
  Hyponatraemia 7(3.9) 5 (2.8)
  Hypophosphataemia 11 (6.2) 7(3.9)
PSYCHIATRIC DISORDERS
  Agitation 6 (3.4) 16 (8.8)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
  Acute Respiratory Distress Syndrome   6 (3.4) 7 (3.9)
  Nosocomial Pneumonia 20 (11.2) 17 (9.4)
  Pneumothorax NOS 1 (0.6) 8 (4.4)
  Respiratory Failure 3 (1.7) 6 (3.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
  Decubitus Ulcer 6 (3.4) 5 (2.8)
  Rash NOS 10 (5.6) 11 (6.1)
VASCULAR DISORDERS
  Hypertension NOS 14 (7.9) 6 (3.3)
  Hypotension NOS 17 (9.6) 12 (6.6)
* Clinically significant upper gastrointestinal bleeding was considered a serious adverse event but it is not included in this table.
NOS = Not otherwise specified.

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.

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitation, elevated blood pressure, and peripheral edema.

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, flatulence, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, dry mouth, stomatitis and abdominal swelling. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued. Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison 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: Mild and, rarely, marked elevations of liver function tests [ALT (SGPT), AST (SGOT), γ-glutamyl transpeptidase, alkaline phosphatase, and bilirubin (jaundice)]. In rare instances, overt liver disease has occurred, including hepatocellular, cholestatic, or mixed hepatitis, liver necrosis (some fatal), hepatic failure (some fatal), and hepatic encephalopathy.

Infections and Infestations: Clostridium difficile associated diarrhea.

Metabolism and Nutritional Disorders: Hyponatremia, hypoglycemia, hypomagnesemia, and weight gain.

Musculoskeletal: Muscle cramps, myalgia, muscle weakness, joint pain, bone fracture, and leg pain.

Nervous System/Psychiatric: Psychic disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, dream abnormalities; vertigo; paresthesia; and hemifacial dysesthesia.

Respiratory: Epistaxis, pharyngeal pain.

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (TEN; some fatal), Stevens-Johnson syndrome, and erythema multiforme (some severe); purpura and/or petechiae (some with rechallenge); skin inflammation, urticaria, angioedema, pruritus, photosensitivity, alopecia, dry skin, and hyperhidrosis.

Special Senses: Tinnitus, taste perversion.

Ocular: Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis and double vision.

Urogenital: Interstitial nephritis (some with positive rechallenge), urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine, proteinuria, hematuria, glycosuria, testicular pain, and gynecomastia.

Hematologic: Rare instances of pancytopenia, agranulocytosis (some fatal), thrombocytopenia, neutropenia, leukopenia, anemia, leucocytosis, and hemolytic anemia have been reported.

The incidence of clinical adverse experiences in patients greater than 65 years of age was similar to that in patients 65 years of age or less.

Additional adverse reactions that could be caused by sodium bicarbonate include metabolic alkalosis, seizures, and tetany.