The clinical safety of omeprazole.

This review comprises data from more than 19,000 individuals who have taken part in clinical studies of omeprazole. Isolated, non-specific adverse events which might be attributable to omeprazole have included nausea, dizziness, headache and diarrhoea. These events have been generally mild and transient and have not usually required either a reduction of dose or cessation of therapy. The frequency and spectrum of adverse events have been the same in those over 65 years of age as in younger patients. No drug-related adverse events have been found in patients with renal insufficiency or severe liver failure. More than 1.2 million patient treatments of omeprazole have now been given. The overall incidence of adverse events with omeprazole is low, and in comparative studies has been in the same range as that found with H2-receptor antagonists. Importantly, no dose-related adverse events have been observed with omeprazole in the dose range 10-60 mg/day. Furthermore, none of the serious adverse events that have been reported have been attributable to omeprazole. No histological changes in oxyntic endocrine cells have been found after short-term periods of treatment with either omeprazole or H2-receptor antagonists in patients with peptic ulcer disease. Long-term continuous high-dose omeprazole treatment of patients with Zollinger-Ellison syndrome has not induced any significant increase in the oxyntic endocrine cell hyperplasia. Investigations of the gastric mucosa from patients in a compassionate use programme who have received omeprazole, usually 20 mg daily, for periods of up to 37 months, have been performed. Two hundred and forty-eight patients had their last biopsy taken after at least 11 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical safety of omeprazole.

An assessment of the safety of omeprazole treatment based on data from more than 13,000 patients and subjects is given. Treatment times were up to 6 years and daily doses of up to 360 mg were administered. The incidence of serious adverse events reported in comparative short-term studies with H2-receptor antagonists and placebo were similar. No specific pattern of symptoms could be ascribed to omeprazole. In addition, serious adverse events reported in long-term studies with omeprazole did not indicate any specific drug-related effects. The spectrum of subjective side-effects (non-serious) reported in a large number of comparative studies with H2-receptor antagonists did not differ between the drugs. The laboratory data obtained during omeprazole therapy revealed no clinically significant effects in any parameter studied. Omeprazole did not influence blood pressure, heart rate or ECG.

Omeprazole in the treatment of Zollinger-Ellison syndrome: a 4-year international study.

The H+, K(+)-ATPase inhibitor omeprazole has been made available on a compassionate basis for patients with Zollinger-Ellison syndrome considered resistant to, or with side-effects on, histamine H2-receptor antagonists. By December 1985, the first 80 patients, from 46 centres in 11 countries, had been treated for periods of 2 days to 4 years. Basal acid output was decreased to the desired level of less than 10 mmol.hour-1, and symptoms were rapidly relieved. Acid secretion and laboratory variables were checked regularly and endoscopic examinations made at intervals. Dosage was adjusted primarily on the basis of basal acid output, but also if symptoms recurred. The starting dose was generally 60 mg daily and the median dose ranged between 60 and 70 mg daily over the study period. There was no evidence of tachyphylaxis. More than 90% of the patients were successfully controlled on total daily doses of 120 mg or less; one-third of patients required divided doses. Tolerance was good: there were no obvious drug-related effects on laboratory variables, including fasting serum gastrin, and there were very few adverse events. Thirteen patients died (11 of the primary disease and two of other causes), four underwent successful tumour resection, six underwent total gastrectomy (though acid secretion was controlled in five), four patients' treatment was changed to other medical therapy, and one was lost to follow-up. Omeprazole thus appears to be both safe and very effective in controlling acid hypersecretion in this group of patients, and to provide a suitable alternative to total gastrectomy.

Safety aspects of omeprazole.

Omeprazole has been given to more than 2500 subjects, mostly in short-term studies for 2-4 weeks, but also to some patients for more than 2 years. An analysis of side-effects has so far not shown a specific pattern that could be attributed to the drug.

Gastric emptying and absorption of acetylsalicylic acid administered as enteric-coated micro-granules.

Enteric-coated and uncoated microgranules of acetylsalicylic acid (ASA), labelled with 51Cr, were administered orally to six healthy male volunteers in a cross-over study. Gastric emptying was studied using a profile scanning radiation technique. Absorption of ASA was followed by measuring the plasma concentration of salicylate. Gastric emptying both of uncoated and enteric-coated granules varied considerably between individuals, but in most cases was gradual and extended over a period of several hours. The median time until 50% and 90% were emptied from the stomach was 1 and 3-3.5 h, respectively, for both the uncoated and enteric-coated granules. The absorption of ASA from the uncoated granules occurred in parallel with the gastric emptying. However, with the enteric-coated granules, absorption was delayed for about 3 h after gastric emptying. It was concluded that the slow absorption of ASA from enteric-coated granules could be explained partly by gradual gastric emptying and partly by slow dissolution of the ASA granules in the intestine.

Iron prophylaxis in menorrhagia.

Heavy menstrual bleedings frequently lead to iron deficiency. Iron supplementation is usually given to cover the increased losses. In the present study one tablet containing 100 mg of iron (Duroferon R, Durules R) was given daily for 10 days in connection with the menstrual period in 15 women with menorrhagia. The tablets contained 59 Felabelled FeSO4 and the total absorption was measured in a whole-body counter. The mean menstrual blood loss was 117 ml (range 46-259 ml), corresponding to 53 mg of iron (range 21-117 mg). The mean absorption was 81 mg (range 49-145 mg). Individually, 14 of 15 subjects absorbed more iron from the tablets than was lost by the menstrual bleedings. Thus, the iron prophylaxis as applied in the present study seems to be sufficient in most women with menorrhagia.

Systemic capillary leak syndrome with monoclonal IgG and complement alterations. A case report on an episodic syndrome.

A case of the rare systemic capillary leak syndrome (SCLS) is described. The patient suffered 9 attacks with muscle pain, weakness and profuse sweating. He showed increased Hct values up to 79 percent and a decreasing plasma volume to about 50 percent of normal. During the attacks the patient was in a state of shock and BP was unmeasurable. Studies with 131I-labelled albumin during attack showed an increased transcapillary escape rate to about 20 percent/hour, compared to 6 percent when he was without symptoms. A monoclonal IgG with a constant concentration of about 5g/l was found. Studies of the complement system during attack showed low C4 values, disproportions among the C1 subcomponents and C1r-C1s-C1IA complexes, suggesting a complement activation via the classic pathway. Hereditary angio-edema was excluded by normal C1IA values. The complement activation might be part of the pathogenesis of the increased macromolecular permeability in this syndrome. A short review of cases described earlier is given.

Food iron absorption in iron deficiency.

The absorption of food iron in relation to the diet was studied in 10 phlebotomized normal young male subjects during 3 to 5 months. The iron absorption was calculated from the net increase of the hemoglobin mass. There was pronounced individual variation in the mean dietary absorption ranging between 1.9 and 5.0 mg. There was no correlation between the amount of iron absorbed and the amount of iron ingested. There was no apparent influence of a high or a low intake of animal products, cereals, vegetables, tea, or alcohol on the individual absorption values. A negative correlation between the iron absorption and the total amount of fecal dry substance was observed. This might be ascribed to an influence of dietary fibers on the absorption of food iron.

Haemoglobin synthesis following injection of iron-poly (sorbitol-gluconic acid) complex, Ferastral.

Ferastral, a new iron-poly (sorbitol-gluconic acid) complex for parenteral use has been given to 22 patients with iron deficiency anaemia. The patients were divided in two groups. Group I received a suboptimal dose of Ferastral iron corresponding to 90% of the iron calculated to normalize the haemoglobin value. Increases in total haemoglobin and also blood losses were measured. The availability of the injected iron for haemoglobin synthesis ranged from 63% to 111%. Group II received an amount of Ferastral-iron calculated to be necessary for normalization of the haemoglobin plus an additional 500 mg of Ferastral-iron. In this group the haemoglobin increase was rapid. In 7 weeks 10 out of 14 patients had reached a normal haemoglobin level.

Iron absorption in patients with dermatitis herpertiformis.

Iron absorption has been studied in patients with dermatitis herpetiformis (DH). Four patients out of 20 had iron deficiency, defined as absence of or only traces of haemosiderin in bone marrow smears. These four had adequate absorption of ferrous iron. The iron deficiency in at least 3 of them was ascribed to increased iron loss. The results indicate that, although having a mild to moderate malabsorption syndrome, DH patients can be expected to exhibit adequate absorption of orally administered iron. Explanations of a negative iron balance other than defective absorption should therefore be sought.

Gastrointestinal blood loss in man during administration of two ampicillin esters.

The gastrointestinal blood loss during intake of two ampicillin esters (pivampicillin and bacampicillin) was studied in 10 male volunteers. A radioactive chromium method was used. The study was performed with a double-blind cross-over technique. Pivampicillin seemed to give a slightly higher increase in gastrointestinal blood loss compared to placebo and bacampicillin but these bleedings are probably of no clinical significance.

A comparative study of gastrointestinal bleeding during administration of ketoprofen and naproxen.

The gastrointestinal blood losses arising after ketoprofen and naproxen therapy were studied in 12 male volunteers. A 51Cr-technique was used and the study was carried out using a double-blind crossover design. The median daily blood losses were 3.3 and 1.2 ml after ketoprofen and naproxen, respectively. Both preparations caused significantly increased gastrointestinal blood losses compared with preceding control periods, but there was no statistically significant difference between the two preparations.

Serum iron increase as a measure of iron absorption - studies on the correlation with total absorption.

The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter. Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.