Omeprazole

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Inhibition of the cytochrome p450 enzyme system by omeprazole, especially in high dose, may cause a decrease in the hepatic metabolism of /coumarin- or indandione-derivative anticoagulants, diazepam or phenytoin/ which may result in delayed elimination and increased blood concentrations, when these medications are used concurrently with omeprazole.

Omeprazole may increase gastrointestinal pH; concurrent use /of ampicillin esters, iron salts, or ketoconazole/ with omeprazole may result in a reduction in absorption of ampicillin esters, iron salts, or ketoconazole.

Concurrent use of omeprazole with /bone marrow depressants/ may increase the leukopenic and/or thrombocytopenic effects of both these medications; if concurrent use is required, close observation for toxic effects should be considered.

The effect of omeprazole on drug metabolism was studied using the model drugs antipyrine and (14)C-aminopyrine. Elimination of both model drugs was assessed before and after 15 days of therapy in male subjects. It was concluded that metabolic inhibition of the model drugs would not occur with normal clinical doses of omeprazole.

For more Interactions (Complete) data for OMEPRAZOLE (9 total), please visit the HSDB record page.

Despite their wide use, omeprazole and esomeprazole have only rarely been associated with hepatic injury. In large scale, long term trials , serum ALT elevations occurred in less than 1% of patients and at rates similar to those that occurred with placebo or comparator drugs. A small number of cases of clinically apparent liver disease due to omeprazole or esomeprazole have been published, the frequency of these cases probably being less than 1:100,000 users. A somewhat characteristic clinical phenotype has been described, with most cases arising during the first 1 to 4 weeks of therapy and being marked by an acute hepatocellular pattern of injury, with rapid recovery upon withdrawal. Rash, fever and eosinophilia were rare, as is autoantibody formation. Liver biopsy typically shows prominent centrolobular necrosis, suggestive of an acute, toxic hepatic injury (acute hepatic necrosis); however, recurrence upon rechallenge has been documented in several cases. In some instances, other organ involvement is prominent including rhabdomyolysis, lactic acidosis, renal insufficiency or Stevens Johnson syndrome. In large case series of drug induced liver injury, omeprazole and esomeprazole have accounted for few instances of symptomatic acute liver injury and rare instances of acute liver failure.

The delayed-release capsule are enteric-coated (as omeprazole is acid-labile) so the absorption of omprazole begins once the granules leave the stomach. Absorption is rapid. Peak plasma levels occur within 0.5 - 3.5 hours. The absolute bioavailability (compared with intravenous administration) of the delayed-release capsule is 30-40% at doses of 20 - 40 mg, due to presystemic metabolism. This value increases slightly when given repeatedly. Based on a relative bioavailability study, the AUC and Cmax of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively. Interestingly, when the 40 mg delayed release capsule is given with or without applesauce, it is bioequivalent. However, when the 20 mg delayed release capsule is given with the same conditions, it is not bioequivalent. When the same capsule is given to the elderly, bioavailability increases. Omeprazole was 76% bioavailable.

Omeprazole is distributed into human milk; following oral administration of omeprazole 20 mg in one lactating women, concentrations of the drug were measured in breast milk.

The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. ... Peak omeprazole concentrations in breast milk (58 nM, 3 hr after ingestion) were less than 7% of the peak serum concentration (950 nM at 4 hr), indicating minimal secretion.

Omeprazole overdose of up to 2400 mg (120 times higher than the recommended clinical dose) has been reported. The adverse reactions like confusion, drowsiness, tachycardia, blurred vision, headache, dry mouth, nausea, vomiting, diaphoresis, and flushing were seen with overdose. These symptoms were transient, and no serious clinical outcomes were observed with monotherapy. No specific antidote for omeprazole overdosage is known. Dialysis may not be helpful as omeprazole is extensively protein-bound. Symptomatic and supportive care is recommended with an overdose.

Omeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H⁺/K⁺-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity.

/SIGNS AND SYMPTOMS/ Clinical Effects of Overdose: The following effects have been selected on the basis of their potential clinical significance (not necessarily inclusive: Blurred vision; confusion; diaphoresis (increased sweating); drowsiness; dryness of mouth; flushing; headache; malaise (generally feeling of discomfort or illness); nausea; tachycardia (fast /heart beat/ or /arrhythmia/ irregular heartbeat).

/CASE REPORTS/ We observed a serious symptomatic hepatocellular liver injury in an 85-year-old man treated with omeprazole for many years. Peak values for AST, ALT and AP were 1542 U/L (normal range 14-50), 1236 U/L (11-60) and 154 U/L (30-125) respectively. Abdominal CT scan was normal and viral serologic testing was negative. Omeprazole was discontinued and liver enzymes normalized in 12 days. The patient was known to suffer from ischemic heart disease and had had a myocardial infarction 6 months previously. He was reexposed to omeprazole and the level of liver enzymes rose again and normalized after stopping omeprazole. Despite the improvement of his liver function, the patient died 5 days later due to chronic congestive heart failure. Five cases of omeprazole-induced liver injury have been reported to the Swiss Drug Regulatory Agency since 1990, among them two of cholestatic hepatitis and one of hepatic failure. The WHO Data Base has collected 13,630 ADRs related to omeprazole, with more than 80 cases of hepatitis, 60 of jaundice and about 40 of cholestatic hepatitis. Clinical studies reported minimal increase of liver enzymes only, in 1-5% of cases. This case with reexposure, together with those reported internationally, suggests that hepatitis is a possible but obviously rare complication of omeprazole treatment.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Omeprazole

vLess-DILI-concern

4

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In two 2 year studies in rats, omeprazole, given in doses corresponding to 4 to 352 times the human dose, caused end-life gastric carcinoid tumors and enterochromaffin-like cell hyperplasia in a dose-related manner in both male and female animals. These enterochromaffin-like cell changes have been shown to be caused by high levels of gastrin (or hypergastrinemia). Pronounced acid inhibition at extremely high doses of gastric acid pump inhibitors or H2-receptor antagonists results in the same feedback elevation of gastrin and subsequent enterochromaffin-like cell changes of the stomach.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in pregnant rats did not show omeprazole to have any teratogenic potential at doses 345 times the human dose. Omeprazole produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions in rabbits receiving 17 to 172 times the human dose. In rats, dose-related embryo/fetal toxicity and postnatal development toxicity were observed in offspring resulting from parents treated with 35 to 345 times the human dose.

/GENOTOXICITY/ Omeprazole, was evaluated for its genotoxic effects in both rat and human cultured cells and in the intact rat. DNA repair synthesis, was detected in primary cultures of metabolically competent rat hepatocytes exposed to concentrations ranging from 10 to 100 mg/l, but the responses cannot be considered as clearly positive. Under the same experimental conditions any significant evidence of DNA repair was absent in primary hepatocytes from two human donors. At the same concentrations a modest but dose-related increase of micronucleated cells, that reached the level of statistical significance at 33 mg/l, was present in primary rat hepatocytes and in one of two human donors. In human lymphocytes exposed to subtoxic concentrations ranging from 0.78 to 12.5 mg/l a reproducible concentration dependent clastogenic effect was absent. In partially hepatectomized female rats treated with a single p.o. dose of 1000 mg/kg, the frequency of micronucleated cells was 5.2-fold higher than in controls in the liver, but only 2.0-fold higher in polychromatic erythrocytes of the bone marrow. In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl omeprazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Oral dosage form new animal drugs. Omeprazole. Indications for use: for treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks of age and older.

Antiulcer agent

Medication

Medication (Vet)

Use (kg; approx.) in Germany (2009): >1000

Use (kg; approx.) in Germany (2009): >25000

Omeprazole is indicated for the treatment of duodenal ulcers, benign gastric ulcers, gastroesophageal reflux disease (GERD), heartburn and other symptoms associated with GERD, erosive esophagitis, and long-term treatment of pathological hypersecretory conditions like Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis.

Oral: Capsules, delayed-release (containing enteric-coated granules): 10 mg Prilosec (AstraZeneca); 20 mg Prilosec (AstraZeneca); 40 mg Prilosec (AstraZeneca).

Trade names: Antra, Gastrogard, Gastroloc, Losec, Mepral, Mopral, Omepral, Omeprazen, Parizac, Pepticum, Prilosec, Zoltum.

Oral: Tablets, delayed-release: 20 mg (of omeprazole) Prilosec OTC (Procter & Gamble). /Omeprazole magnesium/

Pyridine N-oxides are important as synthetic intermediates in the manufacture of pharmaceuticals and agrochemicals. The antiulcer agent omeprazole is produced from 2,3,5-trimethylpyridine N-oxide.

Preparation: UK Junggren, SE Sjostrand, EP 5129; US 4255431 (1979, 1981 both to AB Hassle)