Lansoprazole

Possible interactions of lansoprazole with medications known to be metabolized by the hepatic cytochrome p450 enzyme system should be considered.

... Lansoprazole, by increasing gastric pH, as the potential to affect the bioavailability of any medication whose absorption is pH-dependent. Also, lansoprazole may prevent the degradation of acid-labile drugs.

Lansoprazole causes prolonged inhibition of gastric acid secretion, and thereby my interfere with the absorption of these medications /ampicillin ester, digoxin, iron salts, ketoconazole/and other for which bioavailability is determined by gastric pH.

Lansoprazole appears to produce a dose-dependent decrease in the absorption of cyanocobalamin; this my be due to lansoprazole-induced hypochlorhydria or achlorhydria.

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

Despite its wide use, lansoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of lansoprazole, serum ALT elevations have occurred in less than 1% of patients and at rates similar to those that occur with placebo or comparator drugs. Only a small number of cases of clinically apparent liver disease due to lansoprazole or dexlansoprazole have been published and most have been anicteric and mild. In most instances, the time to onset was within 2 to 4 weeks and the pattern of enzyme elevations was hepatocellular or mixed. Hypersensitivity reactions with fever, rash and eosinophilia have been described due to dexlansoprazole and lansoprazole, and these reactions may be accompanied by minor serum enzyme elevations and thus qualify for DRESS syndrome (drug-rash with eosinophilia and systemic symptoms). Autoantibody formation is rare. Recovery is usually rapid (within a month) and complete upon stopping lansoprazole. Recurrence on reexposures has been reported.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Lansoprazole

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat. Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically. Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%). Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Leydig cell tumors (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of 14(C)testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In 2 year studies in rats receiving up to 40 times the recommended human dose, lansoprazole produced dose-related gastric enterochromaffin-life (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. Lansoprazole also increased the incidence of intestinal metaplasia of the gastric epithelium, and produced dose-related increases in the incidence of testicular interstitial adenomas. In a 1 year toxicity study in rats receiving 13 times the recommended human dose, testicular interstitial cell adenoma also occurred in 1 of 30 rats. In a 2 year study in mice receiving up to 80 times the recommended human dose, lansoprazole produced an increased incidence of liver tumors (Hepatocellular adenomas and carcinomas), a dose-related increase in the incidence of gastric ECL cell hyperplasia, and adenomas of the rete restis in males.

Lansoprazole

0.3

1.5

The recommended dose for treating frequent heartburn is 15 mg daily for 14 days.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 15 mg/day, Lowest Therapeutic Dose (LTD): 0.2 mg/kg-day, and Screening Dose: 0.00006 mg/kg-day.

13-Aug-21

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

Antiulcerative

Medication

Use (kg; approx.) in Germany (2009): >750