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omeprazole (Prilosec, Zegerid, Losec, Medral)

Tradename: Prilosec, Losec in Canada, Medral in Mexico (over the counter 2003) Indications: 1) short-term treatment of severe erosive esophagitis 2) short-term treatment of gastroesophageal reflux disease 3) pathologic hypersecretory conditions 4) duodenal ulcer 5) dyspepsia, superior to ranitidine [9] 6) component of multidrug regimen used to treat H pylori Dosage: 1) 20 mg PO QD 2) pathologic hypersecretory conditions a) start 60 mg PO QD b) doses up to 120 mg TID have been used c) administer daily doses > 80 mg BID or TID 3) take before 30 minutes before eating [17] 4) capsule should be swallowed whole, not chewed, crushed or opened Capsules: 10 mg, 20 mg, 40 mg. Tabs: (OTC form 20 mg tablets (Mg+2 salt) {$1/tab, 2003}) [6] Injection: ? for IV infusion (same dose as PO) [7] Zegerid: powder for oral suspension (immediate release) 20 mg packets (460 mg Na+/packet) Pharmacokinetics: 1) decreased stability in acid pH; capsules consist of enteric-coated granules 2) protein-binding 95% 3) extensively metabolized in the liver - metabolized by cyt P450 2C19 - inhibits cyt P450 2C19 4) elimination 1/2life: 0.5-1.5 hours Adverse effects: 1) common (1-10%) - headache, diarrhea, nausea, abdominal pain, dizziness, vomiting, rash, constipation, cough, asthenia, back pain, urinary tract infection 2) uncommon (< 1%) - fever fatigue, malaise, abdominal swelling, chest pain, tachycardia, bradycardia, hypertension, anorexia, irritable colon, flatulence, hypoglycemia, myalgia, weight gain, tremors, nervousness, rash, agranulocytosis, pancytopenia, thrombocytopenia, neutropenia, anemia, leukocytosis 3) increased risk of hip fracture [15] - see drug adverse effects of proton pump inhibitors 4) tubulointerstitial nephritis [16] 5) no increased risk of heart attack [11] * Omeprazole produced dose-related increase in gastric carcinoid tumors in rats (long term, 2 year study). * short-term studies in humans (up 2-11 years) have not detected an increase risk of gastric tumors [3]. Drug interactions: 1) decreased absorption of ketoconazole & itraconazole due to increase in gastric pH 2) increased 1/2life of diazepam (25-50%) [5] 3) increased serum levels of: a) phenytoin b) warfarin 4) any drug which inhibits cyt P450 2C19 can increase omeprazole levels 5) omeprazole inhibits cyt P450 2C19 a) may increase levels of drugs metabolized by cyt P450 2C19 b) may inhibit its own metabolism 6) omeprazole induces cyt P450 1A2 -> may diminish levels of drugs metabolized by cyt P450 1A2 7) omeprazole may diminish antiplatelet effect of clopidogrel via inhibition of cyt P450 2C19 - may cut effect of clopidogrel in half [13] - clopidogrel requires activation by cyt P450 2C19 - pantoprazole & lansoprazole do not inhibit cyt P450 2C19 Test interactions: - hypergastrinemia occurs secondary to hypochlorhydria Mechanism of action: 1) proton pump inhibitor 2) interacts with sulfhydryl groups in proton pump 3) inactive at neutral pH

Interactions

drug interactions drug adverse effects of proton pump inhibitors (PPI)

Related

cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2) cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19)

Specific

esomeprazole (Nexium)

General

proton pump inhibitor pyrrole

Properties

INHIBITS: H+/K+ ATPase MISC-INFO: elimination route LIVER 1/2life 0.5-1.5 HOURS protein-binding 95% pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM cid=4594

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
    1. Journal Watch, Mass Med Soc 20(11):88 (June) 2000
    2. Klinkenberg-Knoll et al Gastroenterology 118:661, 2000
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 9(12):67 2002
  6. Prescriber's Letter 10(12):69 2003
  7. Barkun A et al, Ann Intern Med 139:843, 2003 PMID: 14623622
  8. Prescriber's Letter 11(12): 2004 New Formulation: Zegerid (Omeprazole Powder for Oral Suspension) Detail-Document#: 201208 (subscription needed) http://www.prescribersletter.com
  9. Journal Watch 25(17):140, 2005 Veldhuyzen van Zanten SJ, Chiba N, Armstrong D, Barkun A, Thomson A, Smyth S, Escobedo S, Lee J, Sinclair P. A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study. Am J Gastroenterol. 2005 Jul;100(7):1477-88. PMID: 15984968
  10. Department of Veterans Affairs, VA National Formulary
  11. FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Omeprazole
  12. Prescriber's Letter 14(9): 2007 Preliminary information for Prilosec and Nexium Safety Review Detail-Document#: 2309205 (subscription needed) http://www.prescribersletter.com
  13. Prescriber's Letter 15(11): 2008 Detail-Document#: 241114 (subscription needed) http://www.prescribersletter.com
  14. FDA Alert, 11/17/2009 Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC) http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm
  15. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  16. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  17. NEJM Knowledge+

Component-of

amoxicillin/clarithromycin/omeprazole aspirin/omeprazole magnesium hydroxide/omeprazole/sodium bicarbonate omeprazole/sodium bicarbonate