Omeprazole

Brand Names: Losec, Prilosec

Clinical Names: Omeprazole

Summary

generic name: Omeprazole

trade names: Losec^®, Prilosec^®

type of drug: Omeprazole blocks production of stomach acid as H(+)-K(+)-ATPase proton pump inhibitor.

used to treat: esophageal reflux disease, esophagitis, gastric and duodenal ulcers, and Zollinger-Ellison syndrome

overview of interactions:
• nutrient affected by drug: Vitamin B12 (Cobalamin)

• nutrient affected by drug: Iron

• food reducing drug side effects: Vaccinium macrocarpon (Cranberry)



Interactions

nutrient affected by drug: Vitamin B12 (Cobalamin)

• mechanism: Omeprazole binds in its active form in the parietal cells of the gastric mucosa with the H+,K+-ATPase. This enzyme is responsible for the pumping of protons into the gastric lumen in exchange for potassium ions ("proton pump"). By design omeprazole leads to a dose dependent inhibition of gastric acid secretion. This in turn will interfere with protein absorption. Consequently concern has been raised that prolonged omeprazole therapy could be responsible for a cobalamin deficiency due to protein-bound dietary vitamin B12 malabsorption.
(Bellou A, et al. J Intern Med 1996 Sep;240(3):161-164; Saltzman JR, et al. J Am Coll Nutr 1994;13:584-591.)

• research: Several studies have found that omeprazole interferes with the absorption of vitamin B12 from food sources. Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients treated with H(+)-K(+)-ATPase inhibitors such as omeprazole should have serum vitamin B12 levels monitored. However, other researchers, such as Koop, have come to different conclusions.
(Marcuard SP, et al. Ann Intern Med 1994;120:211-215; Termanini B, et al. Am J Med 1998;104:422-430; Koop H, et al. J Clin Gastroenterol 1992;14:288-292.)

• nutritional support: Supplemental forms of B12 do not require stomach acid to achieve proper absorption. Consequently, individuals using Omeprazole can enhance their B12 status through the use of vitamin B12 in the form of a nutritional supplement or physician-administered injection.

nutrient affected by drug: Iron

• mechanism: Gastric acid secretion is important for absorption of dietary non-heme iron. Consequently there has been concern that long-term use of omeprazole might result in iron deficiency.

• research: Koop et al found that iron, vitamin B12, and folic acid malabsorption is unlikely to occur, at least within the initial 3-4 years of continuous omeprazole therapy. Further, continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.
(Koop H, Bachem MG. J Clin Gastroenterol 1992 Jun;14(4):288-292; Stewart CA, et al. Aliment Pharmacol Ther 1998 Jan;12(1):83-98.)

food reducing drug side effects: Vaccinium macrocarpon (Cranberry)

• nutritional support: Individuals using omeprazole can improve their dietary absorption of protein-bound vitamin B12 by consuming an acidic drink such as cranberry juice at the same time as foods containing vitamin B12.
(Saltzman JR, et al. J Am Coll Nutr 1994 Dec;13(6):584-591.)

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References

Bellou A, Aimone-Gastin I, De Korwin JD, Bronowicki JP, Moneret-Vautrin A, Nicolas JP, Bigard MA, Gueant JL. Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med 1996 Sep;240(3):161-164.
Abstract: The first case of cobalamin deficiency with megaloblastic anaemia in a patient under long-term omeprazole therapy is presented. This patient received omeprazole at a daily dose of 40-60 mg for 4 years as treatment for a gastro-oesophagal reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All other assimilation tests were normal except an expiratory hydrogen breath test performed with lactulose. The haematological status was restored after intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole therapy can be responsible for a cobalamin deficiency due to protein-bound cobalamin malabsorption.

Dutta SK. Vitamin B12 malabsorption and omeprazole therapy. J Am Coll Nutr 1994 Dec;13(6):544-545. (Comment)

Koop H. Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole. Aliment Pharmacol Ther 1992 Aug;6(4):399-406.
Abstract: Metabolic sequelae of profound and long-lasting inhibition of gastric acid secretion by omeprazole have largely been neglected. Data from long-term studies suggest that vitamin B12 stores decrease slightly over several years, although this was not clinically relevant within the first 4 years of therapy. Additionally, it cannot be completely ruled out that patients with an increased iron demand may develop iron deficiency, but data available at present do not provide any evidence that iron malabsorption is to be expected under normal conditions. Protein homeostasis and calcium metabolism seem to be unaffected by long-term omeprazole therapy. Based upon present experience, serum cobalamin concentration should be monitored in patients undergoing omeprazole therapy for several years.

Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol 1992 Jun;14(4):288-292.
Abstract: Since gastric acid plays an important role in the absorption process of iron and vitamin B12, we determined levels of iron, ferritin, vitamin B12, and folic acid in 75 serum samples obtained during continuous omeprazole therapy (6-48 months after start of therapy) from 34 patients with peptic diseases (primarily reflux esophagitis). Serum iron and ferritin levels were decreased in two and three patients, respectively, but there is little evidence that omeprazole administration was causally related to these findings. Serum vitamin B12 and folic acid levels were normal in all cases. We conclude that iron, vitamin B12, and folic acid malabsorption is unlikely to occur, at least within the initial 3-4 years of continuous omeprazole therapy.

Lavy NW. Omeprazole and vitamin B12. Ann Intern Med 1994 Jul 1;121(1):74. (Comment)

Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (Vitamin B12). Ann Intern Med 1994 Feb 1;120(3):211-215.
Abstract: OBJECTIVE: To evaluate protein-bound cyanocobalamin (vitamin B12) absorption before and after omeprazole (Prilosec) therapy in healthy male volunteers. DESIGN: Clinical trial in which each volunteer served as his own control. SETTING: Outpatient department of a university medical center. PARTICIPANTS: Ten healthy, male volunteers 22 to 50 years old. INTERVENTION: Each participant had a modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as well as measurements of serum vitamin B12, gastrin, and folate levels. Five patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole daily. After 2 weeks of omeprazole therapy, these tests were repeated. MEASUREMENTS: The modified Schilling test, gastric analysis, serum gastrin level, folate level, and cyanocobalamin level. RESULTS: At the end of the 2-week treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P = 0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40 mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P < 0.05). CONCLUSIONS: Omeprazole therapy acutely decreased cyanocobalamin absorption in a dose-dependent manner.

Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr 1994 Dec;13(6):584-591.
Abstract: OBJECTIVE: To investigate the effects of hypochlorhydria and acidic drink ingestion on protein-bound vitamin B12 absorption in elderly subjects. METHODS: Absorption of protein-bound vitamin B12 was examined in elderly normal subjects (n = 8), and in hypochlorhydric subjects due to omeprazole treatment (n = 8) or with atrophic gastritis (n = 3). Subjects underwent absorption tests of protein-bound vitamin B12 ingested with water, cranberry juice and 0.1 N hydrochloric acid. RESULTS: Protein-bound vitamin B12 absorption was lower in the omeprazole-treated group (0.50%) compared to the normal group (1.21%; p < 0.001). With cranberry juice ingestion, the omeprazole-treated group showed an increase in absorbed protein-bound vitamin B12 (p = 0.025). With dilute hydrochloric acid ingestion, there was a further increase in vitamin B12 absorption (p < 0.001). CONCLUSION: Omeprazole causes protein-bound vitamin B12 malabsorption, and ingestion of an acidic drink improves protein-bound vitamin B12 absorption.

Schenk BE, Festen HP, Kuipers EJ, et al. Effect of short-and long-term treatment with omeprazole on the absorption and serum levels of cobalamin. Aliment Pharmacol Ther 1996;10:541-545.

Stewart CA, Termanini B, Sutliff VE, Serrano J, Yu F, Gibril F, Jensen RT. Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment Pharmacol Ther 1998 Jan;12(1):83-98.
Abstract: BACKGROUND: Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. AIM: To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. METHODS: One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. RESULTS: Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. CONCLUSIONS: Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.

Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen RT. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998 May;104(5):422-430.
Abstract: BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. METHODS: In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. RESULTS: The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. CONCLUSIONS: Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency.