Table 2. Adverse events from approved use of omeprazole that were reported in the studies analyzed, published from 1994 to July 2018.
| Adverse events | Participants (n) | Author, year | |
|---|---|---|---|
| Clinical trials (28) | ADR: Diarrhea, vomiting and circulatory problems | Patients with reflux esophagitis (193) | Bate et al., 199550 |
| ADR: Dyspepsia, flatulence, abdominal pain and diarrhea | Patients with active duodenal ulcer (180) | Marzio et al., 199551 | |
| ADR: Abdominal pain, diarrhea, nausea, headache and respiratory tract infection | Patients with gastric ulcer (520) | Valenzuela et al., 199652 | |
| ADR: Diarrhea, headache, melena, chills and mononucleosis infection plus allergic reaction | Patients with duodenal ulcer (381) | Labenz et al., 199753 | |
| ADR: Stroke, cancer, pulmonary embolism and gastrointestinal bleeding/perforation | Patients with peptic ulcer with bleeding (274) | Muckadell et al., 199739 | |
| ADR: Cardiovascular events such as myocardial infarction, heart failure, stroke, pulmonary embolism, gastrointestinal bleeding and cancer | Patients with peptic ulcer in the stomach or duodenum (333) | Hasselgren et al., 199754 | |
| ADR: Diarrhea, stomatitis, metallic taste in the mouth and abdominal pain | Patients with active gastric or duodenal ulcer (78) | Annibale et al., 199755 | |
| ADR: Epigastric pain, facial erythema and loss of libido | Patients with erosive or ulcerative esophagitis, grade 2 or 3 (231) | Annibale et al., 199856 | |
| ADR: Dizziness, fatigue and aphthous stomatitis | Outpatients with symptoms of reflux esophagitis (70) | Ladas et al., 200057 | |
| TI: Omeprazole failed to control the gastric acidity of some patients | Patients with gastroesophageal reflux disease (88) | Leite et al., 199858 | |
| ADR: Diarrhea, taste disorder, increased levels of liver enzymes and cholecystitis | Patients diagnosed with at least one duodenal ulcer and with a test for H. pylori (539) | Lind et al., 199961 | |
| ADR: Death due to cardiovascular problems | Patients with persistent reflux esophagitis and who did not respond to treatment with H2 receptor antagonists (230) | Klinkenberg-Knol et al., 200060 | |
| ADR: Diarrhea, nausea, headache, cold, vomiting and fever | Patients with gastroesophageal reflux without erosive esophagitis (359) | Richter et al., 200059 | |
| Clinical trials (28) | TI/ADR: Worsening of symptoms; taste disorder and scarlet fever | Patients with chronic functional dyspepsia with or without gastritis due to H. pylori (974) | Blum et al., 200062 |
| ADR: Diarrhea, pericarditis and chest pain | Patients with erosive gastroesophageal reflux cured within 90 days (243) | Thjodleifsson et al., 200063 | |
| ADR: Diarrhea, abdominal pain and headache | Patients with dyspeptic symptoms (73) | Gottrand et al., 200133 | |
| TI: Some patients did not respond to treatment with omeprazole | Patients with dyspepsia (514) | Rabeneck et al., 200264 | |
| ADR: Increased fibroblast growth factor 2 | Patients with gastric neoplasm (16) | Esaki et al., 200265 | |
| ADR: Myocardial infarction, ventral hernia, deep vein thrombosis, miscarriage, headache, respiratory infection, diarrhea and abdominal pain | Patients who suffered with burning in the stomach for at least three months (390) | Armstrong et al., 200566 | |
| ADR: Diarrhea, taste disorders and dyspepsia | Patients infected with H. pylori with abdominal disorders (323) | Manes et al., 200538 | |
| ADR: Nasopharyngitis, upper respiratory tract inflammation, diarrhea, headache, arthralgia, back pain, insomnia, cystitis, abdominal pain and hyperglycemia | Japanese patients with recurrent reflux esophagitis (119) | Ohkusa et al., 200567 | |
| ADR: Allergic reaction | Patients with lymphocytic gastritis (51) | Madisch et al., 200668 | |
| ADR/TI: Headache, somnolence and diarrhea | HIV-negative, healthy patients (19) | Schöller-Gyüre et al., 200832 | |
| ADR: Headache and gastrointestinal disorders | Patients with burning in the stomach or reflux (55) | Howden et al., 200969 | |
| ADR: Increased weight, increased ferritin level, increased death related to cardiac disorders and non-fatal heart attack | Patients with esophageal reflux (310) | Lundell et al., 200970 | |
| ADR: Omeprazole reduced antiplatelet effects | Unmedicated male patients (24) | Ferreiro et al., 201071 | |
| DI: Increased levels of leukocytes and platelets and increased incidence of cardiac and cerebral adverse events | Patients with stent implantation (38) | Hudzik et al., 201072 | |
| ADR: Diarrhea, tiredness, dizziness, abdominal pain and headache | Patients with typical symptoms of reflux more than twice a week (200) | Miwa et al., 201173 | |
| Cohort studies (17) | ADR: Thrombosis, hyperthyroidism, complete retinal detachment, ulcerative colitis and skin rash | Patients with persistent reflux esophagitis and who did not respond to treatment with H2 receptor antagonists (178) | Klinkenberg-Knol et al., 199474 |
| ADR: Death due to cardiovascular, cerebrovascular, respiratory and postoperative problems, carcinomas, urinary tract infections and suicide | Diagnosed with colitis due to C. difficile (140) | Cadle et al., 200713 | |
| ADR: Myocardial infarction, stroke, cardiovascular death and unstable angina | Patients using clopidogrel after percutaneous coronary intervention (16,690) | Kreutz et al., 201075 | |
| DI: Inhibition of the effect of clopidogrel | Patients using clopidogrel (18,139) | van Boxel et al., 201076 | |
| DI: Increased anticoagulant effect of acenocoumarol | Patients that used acenocoumarol for at least 42 days in the study period (2,755) | Teichert et al., 201177 | |
| TI: Cardiovascular death, myocardial infarction and stroke | Patients who underwent coronary intervention (13,144) | Kimura et al., 201178 | |
| ADR: Increased levels of chromogranin A | Patients with increased levels of chromogranin A that could not be caused by neuroendocrine tumors (196) | Korse et al., 201179 | |
| ADR: Hypergastrinemia | Patients with moderate to severe peptic esophagitis | Ligumsky et al., 201180 | |
| TI: Omeprazole failed to control the gastric acidity of some patients | Patients who underwent kidney transplantation | David-Neto et al., 201249 | |
| DI: Inhibition of the effect of clopidogrel | Patients with acute coronary syndrome (37,099) | Lin et al., 201281 | |
| ADR: Increased risk of fractures | Patients who underwent medical consultations in the last two years (61,916) | Soriano et al., 201416 | |
| ADR: Increased risk of dementia | Elderly people over 75 years old (73,679) | Gomm et al., 201644 | |
| ADR: Increased risk of first-time ischemic stroke | - (396,296) | Yi et al., 201747 | |
| ADR: Increased serum creatinine levels | Inpatient patients (419) | Varallo et al., 201841 | |
| ADR: Increased risk of metabolic syndrome and hepatic steatosis | Patients with a recent diagnosis of celiac disease (301) | Imperatore et al., 201845 | |
| ADR: Hypomagnesemia | Hospitalized patients with Torsades de pointes (48) | Lazzerini et al., 201842 | |
| ADR: Increased risk of fibrosis progression, cirrhosis, hepatic decompensation and development of hepatocellular carcinoma | Patients with hepatitis C virus (HCV) infection. | Li et al., 201848 | |
| Quasi-experimental studies (4) | ADR: Diarrhea and ringing in the ears | Patients with burning in the stomach, erosive esophagitis or non-erosive reflux disease (108) | Tsuzuki et al., 201182 |
| ADR: Respiratory infection, otitis media, pharyngitis, change in bowel habit, fever and rhinitis | Patients with cured reflux esophagitis (64) | Hassall et al., 201283 | |
| ADR: Nausea, vomiting, constipation, diarrhea, metallic taste in the mouth, headache, abdominal pain, loss of appetite, drowsiness, weakness, dizziness and dry mouth | Patients with H. pylori (134) | Sezgin et al., 201434 | |
| ADR: Myocardial infarction or heart failure with or without consequent death | Patients who were hospitalized due to myocardial infarction within 12 weeks after starting use of proton-pump inhibitors (5,550) | Juurlink et al., 201384 | |
| Case-control studies (2) | ADR: Maculopapular rash, angioedema and/or urticaria, Steven-Johnson’s syndrome, erythema multiforme, eczematous eruption and urticarial vasculitis | Patients with dyspepsia, gastroesophageal reflux disease and upper gastrointestinal tract bleeding; prevention of ulcers induced by nonsteroidal anti-inflammatory drugs, stress and prednisolone (170) | Chularojanamontri et al., 201285 |
| ADR: Low sperm motility | Men who were planning to have children (955) | Heijgen et al., 201646 | |
| Cross-sectional studies (2) | ADR: Proliferative changes | Patients who underwent endoscopy and who had been using proton-pump inhibitors for at least 2 months (22) | Menegassi et al., 20105 |
| ADR: Decreased serum levels of vitamin B12 | Patients with diagnosis of gastrointestinal disease in the consumption of proton pump inhibitors (109) | Mindiola et al., 201740 | |
| No clinical outcomes | Clinical trials (12) | Many conditions | Yamamoto et al., 199586; Goh et al., 199587; Soga et al., 199937; Noordzij et al., 200188; Zhou et al., 200243; van Zanten et al., 200535; Fujiwara et al., 200589; Liu et al., 201390; Miner JR et al., 201091; Ummarino et al., 201236; Sakurada et al., 201292; Solana et al., 201393 |
| Cohort studies (5) | Many conditions | Zairis et al., 201094; Harjai et al., 201195; Chen et al., 201428; Galante et al., 201296; Wang et al., 201797 | |
| Cross-sectional studies (2) | Newborns with hypospadias born to mothers who had used proton-pump inhibitors during pregnancy (430,569) | Erichsen et al., 201498 | |
| Patients with stage 5 chronic kidney disease (CKD) on hemodialysis therapy and chronic use of proton pump inhibitors (37) | Restrepo et al., 201799 |
ADE = adverse drug event; ADR = adverse drug reaction; DI = drug interaction; TI = therapeutic ineffectiveness.