Omeprazole

Article Author:
Neal Shah
Article Editor:
Pranay Srivastava
Updated:
5/6/2019 8:01:04 PM
PubMed Link:
Omeprazole

Indications

Omeprazole is indicated for the short term treatment of peptic ulcer disease in adults where most patients heal within four weeks.  Patients with duodenal ulcer disease and H. pylori infection disease that is active for up to one year may benefit from combination therapy that includes omeprazole with a macrolide antibiotic.  Studies show a reduction in recurrence of duodenal ulcers when H. Pylori is treated and a reduced rate of clarithromycin resistance with triple therapy.[1][2]  Resistance should be expected and susceptibility testing performed if patients fail treatment and treatment should be adjusted accordingly.

Omeprazole is also indicated for gastric ulcers in adults, and gastroesophageal reflux disease in adults and pediatric populations. Studies have shown the efficacy of omeprazole for short term treatment in erosive esophagitis.[3][4]  Omeprazole is also indicated for healing erosive esophagitis in both adults and children.  Conditions prone to hypersecretion such as Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis also respond to management with omeprazole treatment in adults. 

Mechanism of Action

Omeprazole is a proton pump inhibitor. It inhibits the parietal cell H+ / K+ ATP pump, the final step of acid production. In turn, omeprazole suppresses gastric basal and stimulated acid secretion.  The inhibitory effects of omeprazole occur rapidly, within 1 hour of administration with the maximum effect occurring in 2 hours.  The inhibitory effects last for approximately 72 hours after administration followed by a return to baseline activity in 3 to 5 days.  With daily use of the medication, the effects will plateau at 4 days.

Omeprazole metabolism occurs via the hepatic cytochrome P450 enzyme system; the two primary CYP isozymes involved are CYP2C19 and CYP3A4.  Urinary excretion is a primary route of excretion of omeprazole metabolites.  Omeprazole has a short half-life of a half-hour to an hour in healthy subjects and about three hours for patients with hepatic impairment, but its pharmacological effect lasts much longer since it preferentially concentrates in parietal cells where it forms a covalent linkage with H+/K+ ATPase, which it irreversibly inhibits.[5] 

Administration

The method of delivery for omeprazole is heavily dependent on the diagnosis.

For H. pylori infection, the recommended adult oral regimen is 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg, each given twice daily for 10 days.  If an ulcer is present on initial diagnosis, then it is recommended to provide an additional 18 days of omeprazole 20 mg once daily

The recommended oral adult dose for the treatment of symptomatic GERD absent esophageal lesions is 20 mg daily for up to 4 weeks.  However, if erosive lesions are present, therapy may extend to 8 weeks.

Patients with hypersecretory diseases are recommended to start at 60 mg once daily followed by the individualization of dosage based on patient's need and clinical response.  If the daily dose is higher than 80 mg, the dosage should be divided throughout the day.  Long term treatment with Omeprazole is not recommended, and eventually switching to an H2-inhibitor is preferred.

For pediatric patients between the ages of 1 and 16, the dosage is dependent on the weight of the child.

  • Weight: 5 less than 10 kg, dose:5 mg
  • Weight between 10 and 20 kg, dose:10 mg
  • Weight: over 20 kg, dose: 20 mg

Omeprazole should be ingested 30 to 60 minutes before meals. It may be taken with antacids. When taken twice daily, the first dose should be prior to breakfast and the second dose before dinner. The capsule and tablet should be swallowed whole, not crushed or chewed. However, it is permissible to open the capsule and mix the contents with one tablespoon of applesauce, soft enough to be swallowed without chewing. The suspension should be left to thicken for two to three minutes, following reconstitution and administered within 30 minutes.  Drink with a glass of cool water to ensure complete swallowing of the pellets.

Omeprazole therapy should be at the lowest dose possible for the shortest duration; physicians have looked into deprescribing proton pump inhibitors if patients are on it long term. One group recommends deprescribing PPIs, meaning to reduce the dose, stop completely, or use "on-demand" dosing, in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis, and who have achieved symptomatic resolution. The patient should follow up for monitoring of symptoms at weeks 4 and 12 and again at 6 to 12 months.  But these recommendations do not apply to those who have or have had Barrett's esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers.[6]

Adverse Effects

Omeprazole is considered a benign drug; however, the primary adverse effects of omeprazole include a headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence in adults. The principal adverse effects in the pediatric population are similar to adults; the most frequent events were reportedly fever and respiratory.  Proton pump inhibitors (PPI) therapy may correlate with an increased risk of Clostridium difficile (C. diff) associated diarrhea.[7]  Long-term and multiple daily dose PPI treatment may have connections with an increased risk for osteoporosis-related fractures of the hip, wrist or spine but newer studies show long-term PPI use does not correlate with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture suggesting this relationship is not casual.[8][9]. Some evidence has shown a diminished anti-platelet activity of clopidogrel due to impaired CYP2C19 function when used in conjunction with 80 mg omeprazole.[10] There are rare reports of hypomagnesemia with prolonged treatment with PPIs.[11] Avoid concomitant use of omeprazole with St John’s wort or rifampin and other CYP450 inducers due to the potential reduction in omeprazole concentration. 

Contraindications

Omeprazole is contraindicated in patients with a history of hypersensitivity to the drug or product. It is also contraindicated in patients taking products containing rilpivirine.

Monitoring

Patients should have monitoring for signs and symptoms of gastroesophageal reflux disease and peptic ulcer disease when using omeprazole.  Physicians should also monitor for C. difficile associated diarrhea and hypomagnesia when patients are on omeprazole long term.

Toxicity

There have not been a significant number of omeprazole overdoses which have led to serious medical consequences. There is no specific antidote for an event such as this.

Enhancing Healthcare Team Outcomes

Omeprazole was the first proton pump inhibitor discovered in 1979, and it has revolutionized the management of numerous gastrointestinal diseases.  Its efficacy compared to new proton pump inhibitors has been studied. One study showed the superiority of esomeprazole for the Japanese population, especially with CYP2C19 polymorphism over omeprazole and other proton pump inhibitors.[12]  Studies have shown equivalent efficacy comparing omeprazole and rabeprazole.[13]  Comparative studies with multiple proton pump inhibitors including omeprazole have shown greater cost-effectiveness and management of symptoms when using esomeprazole.[14][15][16]

Healthcare workers including nurse practitioners should avoid empirical prescription of omeprazole, and when prescribed, duration limitations should be as per guidelines.


References

[1] Laine L,Suchower L,Frantz J,Connors A,Neil G, Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials. The American journal of gastroenterology. 1998 Nov;     [PubMed PMID: 9820381]
[2] Prasertpetmanee S,Mahachai V,Vilaichone RK, Improved efficacy of proton pump inhibitor - amoxicillin - clarithromycin triple therapy for Helicobacter pylori eradication in low clarithromycin resistance areas or for tailored therapy. Helicobacter. 2013 Aug;     [PubMed PMID: 23356886]
[3] Bianchi Porro G,Pace F,Peracchia A,Bonavina L,Vigneri S,Scialabba A,Franceschi M, Short-term treatment of refractory reflux esophagitis with different doses of omeprazole or ranitidine. Journal of clinical gastroenterology. 1992 Oct;     [PubMed PMID: 1479161]
[4] Sontag SJ,Hirschowitz BI,Holt S,Robinson MG,Behar J,Berenson MM,McCullough A,Ippoliti AF,Richter JE,Ahtaridis G, Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study. Gastroenterology. 1992 Jan;     [PubMed PMID: 1727744]
[5] Howden CW, Clinical pharmacology of omeprazole. Clinical pharmacokinetics. 1991 Jan;     [PubMed PMID: 2029801]
[6] Farrell B,Pottie K,Thompson W,Boghossian T,Pizzola L,Rashid FJ,Rojas-Fernandez C,Walsh K,Welch V,Moayyedi P, Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Canadian family physician Medecin de famille canadien. 2017 May;     [PubMed PMID: 28500192]
[7] Trifan A,Stanciu C,Girleanu I,Stoica OC,Singeap AM,Maxim R,Chiriac SA,Ciobica A,Boiculese L, Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. World journal of gastroenterology. 2017 Sep 21;     [PubMed PMID: 29085200]
[8] Targownik LE,Lix LM,Metge CJ,Prior HJ,Leung S,Leslie WD, Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2008 Aug 12;     [PubMed PMID: 18695179]
[9] Yanagihara GR,de Paiva AG,Neto MP,Torres LH,Shimano AC,Louzada MJ,Annoni R,de Oliveira Penoni ÁC, Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone. Revista brasileira de ortopedia. 2015 Mar-Apr;     [PubMed PMID: 26229922]
[10] Kenngott S,Olze R,Kollmer M,Bottheim H,Laner A,Holinski-Feder E,Gross M, Clopidogrel and proton pump inhibitor (PPI) interaction: separate intake and a non-omeprazole PPI the solution? European journal of medical research. 2010 May 18;     [PubMed PMID: 20562062]
[11] Toh JW,Ong E,Wilson R, Hypomagnesaemia associated with long-term use of proton pump inhibitors. Gastroenterology report. 2015 Aug;     [PubMed PMID: 25138239]
[12] Sahara S,Sugimoto M,Uotani T,Ichikawa H,Yamade M,Iwaizumi M,Yamada T,Osawa S,Sugimoto K,Umemura K,Miyajima H,Furuta T, Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole. Alimentary pharmacology     [PubMed PMID: 24099474]
[13] Belhocine K,Vavasseur F,Volteau C,Flet L,Touchefeu Y,Bruley des Varannes S, Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole. BMC gastroenterology. 2014 Jul 15;     [PubMed PMID: 25027286]
[14] Çelebi A,Aydın D,Kocaman O,Konduk BT,Şentürk Ö,Hülagü S, Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2016 Sep;     [PubMed PMID: 27782887]
[15] Miner P Jr,Katz PO,Chen Y,Sostek M, Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. The American journal of gastroenterology. 2003 Dec;     [PubMed PMID: 14687806]
[16] Röhss K,Lind T,Wilder-Smith C, Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms. European journal of clinical pharmacology. 2004 Oct;     [PubMed PMID: 15349707]