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Special Alerts
Update to the Labeling of Clopidogrel: Omeprazole Drug Interaction - November 2009
The U.S. Food and Drug Administration (FDA) is alerting healthcare providers to new safety information concerning the interaction between clopidogrel and the proton pump inhibitor (PPI), omeprazole (a known inhibitor of CYP2C19). New studies have demonstrated a 45% reduction in serum concentrations of the active metabolite of clopidogrel when used concurrently with omeprazole. This resulted in up to a 47% reduction in clopidogrel's antiplatelet activity. This reduction occurred when the drugs were given concurrently or if separated by 12 hours.
Other potent CYP2C19 inhibitors that would also be expected to reduce the antiplatelet activity of clopidogrel include cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine. Concurrent use of clopidogrel and these CYP2C19 inhibitors should be avoided. The level of enzyme inhibition varies within the PPI class and the effects of other PPIs on clopidogrel activity are unknown. However, since esomeprazole is an omeprazole metabolite it should also be avoided in patients receiving clopidogrel. The prescribing information for clopidogrel will be updated to reflect this interaction information.
The following are considerations for healthcare providers:
- The concurrent use of clopidogrel and omeprazole should be avoided. Patients receiving clopidogrel for MI or stroke may not receive the expected antiplatelet activity if omeprazole is used concurrently.
- Separating the time of administration of clopidogrel and omeprazole does not reduce the chance of the interaction.
- Concurrent use of cimetidine, esomeprazole, etravirine, felbamate, fluconazole, fluvoxamine, fluoxetine, ketoconazole, voriconazole and ticlopidine should also be avoided because they may also reduce clopidogrel's antiplatelet activity.
- The FDA does not have sufficient drug interaction information to provide recommendations for concurrent use of other PPIs.
- There is no evidence that H2 antagonists (other than cimetidine) interfere with antiplatelet activity of clopidogrel.
- Both cimetidine and omeprazole are available in nonprescription (OTC) forms and patients should be educated to avoid these drugs if receiving clopidogrel.
For more information, healthcare professionals may refer to the following website: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm
Clopidogrel (Plavix®) and Proton Pump Inhibitors (PPIs): Ongoing Safety Review - January 2009; Updated September 2009
The U.S. Food and Drug Administration (FDA) and Health Canada have independently communicated important information regarding an ongoing safety review of clopidogrel and its effectiveness when used with proton pump inhibitors (PPIs).
Clopidogrel is a prodrug requiring hepatic conversion via CYP3A4 and/or CYP2C19 to its active metabolite. Impaired clopidogrel conversion to its active metabolite may be due to either CYP450 polymorphisms or drug-drug interactions resulting in suboptimal antiplatelet activity.
A PPI is often prescribed with the combination of aspirin and clopidogrel to prevent gastrointestinal bleeding. A number of PPIs are available and include dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole. Several studies have reported greater clinical event rates (eg, myocardial infarction, death) or greater platelet reactivity associated with concurrent use of clopidogrel and a PPI (Ho, 2008; Pezella, 2008; Gilard, 2006). Similarly, a prospective, randomized, double-blind trial demonstrated a reduction in antiplatelet activity when omeprazole and clopidogrel are used concurrently (Gilard, 2008). Another controlled trial with the PPI lansoprazole also found evidence of a possible interaction resulting in less antiplatelet activity (Small, 2008). This interaction is thought to result from competitive inhibition of the CYP2C19-mediated activation of clopidogrel by omeprazole and other PPIs, which are all metabolized to at least some degree by CYP2C19. In contrast, one study with esomeprazole and pantoprazole did not find evidence of reduced antiplatelet activity when administered with clopidogrel (Siller-Matula, 2009), highlighting the need for additional studies to determine the degree to which individual PPIs may differ in their potential for interacting with clopidogrel.
The manufacturer of Plavix® has agreed to conduct further studies to better understand the effect of other drugs (including PPIs) and genetic factors on the effectiveness of clopidogrel. The FDA and Health Canada have recommended that healthcare providers continue to prescribe clopidogrel while reevaluating the need for prescription or over-the-counter (OTC) PPIs in patients taking clopidogrel. Patients should continue taking clopidogrel as directed. If taking a PPI with clopidogrel, patients should consult with their healthcare provider. Health Canada recommends against the use of drugs (including PPIs) which inhibit CYP2C19 in patients receiving clopidogrel and is currently working with the manufacturers of clopidogrel to update the Canadian product monograph with this important safety information.
The Clopidogrel Medco Outcomes Study (Stanek, 2009) was presented at the Society for Cardiovascular Angiography and Interventions (SCAI) Annual Scientific Sessions. The study was a retrospective cohort analysis evaluating integrated medical and pharmacy claims. Patients included (n=16,718) were those who had a coronary stent procedure with a new clopidogrel prescription claim within 1 month of procedure. Patients were segregated according to PPI use; newer PPIs (ie, rabeprazole, dexlansoprazole) were not included in the analysis. Those who received a PPI demonstrated a 51% increase in the risk of cardiovascular events (MI, unstable angina, stroke, repeat coronary procedure) compared to those who did not receive a PPI (lansoprazole 24.3%; pantoprazole 29.2%; esomeprazole 24.9%; omeprazole 25.1% vs 17.9%). SCAI has urged healthcare providers to consider prescribing alternatives to PPI use, such as an antacid or H2 blocker (eg, famotidine, ranitidine, or cimetidine). Of note, cimetidine is a moderate CYP2C19 inhibitor. Although no documented interactions exist, theoretically cimetidine may also reduce conversion of clopidogrel to its active metabolite. In cases where gastrointestinal conditions require treatment, the patient's primary care provider or gastroenterologist should be contacted to discuss treatment options.
More recently, a retrospective analysis of the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) trial, an elective PCI trial for patients with angina, and the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel - Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) trial, a PCI trial for patients with moderate-high risk ACS. This analysis revealed that in the PRINCIPLE-TIMI 44 trial, which included 201 patients, 26.4% (n=53) were on a PPI at randomization and the mean inhibition of platelet aggregation at 6 hours after a 600 mg clopidogrel loading dose was significantly lower for patients receiving a concomitant PPI than for those not receiving a PPI (23.2±19.5% vs 35.2±20.9%, p=0.02). Those receiving a 60 mg loading dose of prasugrel demonstrated a modest difference (69.6±13.5% vs 76.7±12.4%, p=0.054). In the TRITON-TIMI 38 trial, which included 13,608 patients, 33% (n=4529) were on a PPI at randomization (pantoprazole 40.7%; omeprazole 36.9%; esomeprazole 13.5 %; lansoprazole 9.7%; rabeprazole 1.4%). In contrast to the MEDCO study, the authors found no association between the use of a PPI and occurrence of the primary endpoint, the composite of cardiovascular death, non-fatal MI, or non-fatal stroke. In addition, patients with a single reduced function CYP2C19 allele receiving a PPI did not demonstrate an increased risk of cardiovascular events. The authors concluded that these findings do not support the need to avoid concomitant use of PPIs, when indicated, in patients receiving clopidogrel or prasugrel (O'Donoghue, 2009).
For more information, healthcare professionals may refer to the following websites:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm
http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/plavix_hpc-cps-eng.php
http://www.scai.org/drlt1.aspx?PAGE_ID=5870
References:
Ho PM, Maddox TM, Wang L, et al, “Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome,” JAMA, 2009, 301(9):937-44.
Pezalla E, Day D, and Pulliadath I, “Initial Assessment of Clinical Impact of a Drug Interaction Between Clopidogrel and Proton Pump Inhibitors,” J Am Coll Cardiol, 2008, 52(12):1038-9.
Gilard M, Arnaud B, Le Gal G, et al, “Influence of Omeprazol on the Antiplatelet Action of Clopidogrel Associated to Aspirin,” J Thromb Haemost, 2006, 4(11):2508-9.
Gilard M, Arnaud B, Cornily JC, et al, “Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind Ocla (Omeprazole Clopidogrel Aspirin) Study,” J Am Coll Cardiol, 2008, 51(3):256-60.
O'Donoghue ML, Braunwald E, Antman EM, et al, “Pharmacodynamic Effect and Clinical Efficacy of Clopidogrel and Prasugrel with or without a Proton-pump Inhibitor: an Analysis of Two Randomised Trials,” Lancet, 2009, 374(9694):989-97, [PMID: 19726078]
Siller-Matula JM, Spiel AO, Lang IM, et al, “Effects of Pantoprazole and Esomeprazole on Platelet Inhibition by Clopidogrel,” Am Heart J, 2009, 157(1):148.e1-5.
Small DS, Farid NA, Payne CD, et al, “Effects of the Proton Pump Inhibitor Lansoprazole on the Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel,” J Clin Pharmacol, 2008, 48(4):475-84.
Stanek EJ, Aubert RE, Flockhart DA, et al, “A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated With Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study,” Society for Cardiovascular Angiography and Interventions 2009 Scientific Sessions; May 6, 2009; Las Vegas, NV.
Medication Safety Issues
Sound-alike/look-alike issues:
Omeprazole may be confused with aripiprazole, fomepizole
Prilosec® may be confused with Plendil®, Prevacid®, predniSONE, prilocaine, Prinivil®, Proventil®, Prozac®
International issues:
Norpramin®: Brand name for desipramine in the U.S.
Pronunciation
(oh MEP ra zole)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes granules for suspension
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Short-term (4-8 weeks) treatment of active duodenal ulcer disease or active benign gastric ulcer; treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD); short-term (4-8 weeks) treatment of endoscopically-diagnosed erosive esophagitis; maintenance healing of erosive esophagitis; long-term treatment of pathological hypersecretory conditions; as part of a multidrug regimen for H. pylori eradication to reduce the risk of duodenal ulcer recurrence
OTC labeling: Short-term treatment of frequent, uncomplicated heartburn occurring ?2 days/week
Use: Unlabeled/Investigational
Healing NSAID-induced ulcers; prevention of NSAID-induced ulcer; stress-ulcer prophylaxis in the critically-ill
Pregnancy Risk Factor
C
Pregnancy Considerations
Crosses the placenta; congenital abnormalities have been reported sporadically following omeprazole use during pregnancy. Based on data collected by the Teratogen Information System (TERIS), it was concluded that therapeutic doses used during pregnancy would be unlikely to pose a substantial teratogenic risk (quantity/quality of data: fair). Because the possibility of harm still exists, the manufacturer recommends use during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to omeprazole or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Atrophic gastritis: Long-term omeprazole therapy has caused atrophic gastritis (by biopsy).
• Carcinoma: In long-term (2-year) studies in rats, omeprazole produced a dose-related increase in gastric carcinoid tumors. While available endoscopic evaluations and histologic examinations of biopsy specimens from human stomachs have not detected a risk from short-term exposure to omeprazole, further human data on the effect of sustained hypochlorhydria and hypergastrinemia are needed to rule out the possibility of an increased risk for the development of tumors in humans receiving long-term therapy.
Disease-related concerns:
• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.
• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of proton pump inhibitors may increase risk of these infections.
• Hepatic impairment: Bioavailability may be increased in patients with hepatic dysfunction; consider dosage reductions, especially for maintenance healing of erosive esophagitis.
Special populations:
• Asian ethnicity: Bioavailability may be increased in patients of Asian descent; consider dosage reductions, especially for maintenance healing of erosive esophagitis.
• Elderly: Bioavailability may be increased in the elderly.
• Pediatrics: Safety and efficacy have not been established in children <1 year of age. OTC use is not approved for children <18 years of age.
Other warnings/precautions:
• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (?7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10-14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey, 2007).
• Self-medication (OTC use): When used for self-medication (OTC), do not use for >14 days; treatment should not be repeated more often than every 4 months.
Adverse Reactions
1% to 10%:
Central nervous system: Headache (3% to 7%), dizziness (2%)
Dermatologic: Rash (2%)
Gastrointestinal: Abdominal pain (2% to 5%), diarrhea (3% to 4%), nausea (2% to 4%), vomiting (2% to 3%), flatulence (?3%), acid regurgitation (2%), constipation (1% to 2%), taste perversion
Neuromuscular & skeletal: Back pain (1%), weakness (1%)
Respiratory: Upper respiratory infection (2%), cough (1%)
1%, postmarketing, and/or case reports (adverse event occurrence may vary based on formulation): Abdominal swelling, abnormal dreams, aggression, agitation, agranulocytosis, alkaline phosphatase increased, allergic reactions, alopecia, ALT increased, AST increased, anaphylaxis, anemia, angina, angioedema, anorexia, anxiety, apathy, atrophic gastritis, benign gastric polyps, bilirubin increased, blurred vision, bradycardia, bronchospasm, chest pain, cholestatic hepatitis, confusion, creatinine increased, depression, diaphoresis, double vision, dry skin, epistaxis, erythema multiforme, esophageal candidiasis, fatigue, fecal discoloration, fever, gastroduodenal carcinoids, GGT increased, glycosuria, gynecomastia, hallucinations, hematuria, hemifacial dysesthesia, hemolytic anemia, hepatic encephalopathy, hepatic failure, hepatic necrosis, hepatitis, hepatocellular hepatitis, hyperhidrosis, hypersensitivity, hypertension, hypoglycemia, hyponatremia, insomnia, interstitial nephritis, irritable colon, jaundice, joint pain, leg pain, leukocytosis, leukopenia, liver disease (hepatocellular, cholestatic, mixed), malaise, microscopic pyuria, mucosal atrophy (tongue), muscle cramps, muscle weakness, myalgia, nervousness, neutropenia, ocular irritation, optic atrophy, optic neuritis, optic neuropathy (anterior ischemic), pain, palpitation, pancreatitis, pancytopenia, paresthesia, peripheral edema, petechiae, pharyngeal pain, photosensitivity, pneumothorax, proteinuria, pruritus, psychiatric disturbance, purpura, skin inflammation, sleep disturbance, somnolence, Stevens-Johnson syndrome, stomatitis, tachycardia, testicular pain, thrombocytopenia, tinnitus, toxic epidermal necrolysis, tremor, urinary frequency, urinary tract infection, urticaria, vertigo, weight gain, xerophthalmia, xerostomia
Metabolism/Transport Effects
Substrate of CYP2A6 (minor), 2C9 (minor), 2C19 (major), 2D6 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2C9 (moderate), 2C19 (strong), 2D6 (weak), 3A4 (weak); Induces CYP1A2 (weak)
Drug Interactions
Atazanavir: Proton Pump Inhibitors may decrease the absorption of Atazanavir. Risk D: Consider therapy modification
Benzodiazepines (metabolized by oxidation): Proton Pump Inhibitors may increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Cilostazol: Omeprazole may enhance the adverse/toxic effect of Cilostazol. Risk D: Consider therapy modification
Clopidogrel: Proton Pump Inhibitors may diminish the therapeutic effect of Clopidogrel. This appears to be due to reduced formation of the active clopidogrel metabolite. Management: Due to the risk for impaired clopidogrel effectiveness, clinicians should carefully consider the need for proton pump inhibitor therapy in patients receiving clopidogrel. Other acid-lowering therapies do not appear to share this interaction. Risk D: Consider therapy modification
Clozapine: Omeprazole may decrease the serum concentration of Clozapine. Omeprazole may increase the serum concentration of Clozapine. Risk C: Monitor therapy
CycloSPORINE: Omeprazole may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
Dabigatran Etexilate: Proton Pump Inhibitors may decrease the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy
Dasatinib: Proton Pump Inhibitors may decrease the absorption of Dasatinib. Risk D: Consider therapy modification
Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination
Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Risk X: Avoid combination
Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Risk C: Monitor therapy
Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Iron Salts: Proton Pump Inhibitors may decrease the absorption of Iron Salts. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk C: Monitor therapy
Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Risk D: Consider therapy modification
Ketoconazole: Proton Pump Inhibitors may decrease the serum concentration of Ketoconazole. Ketoconazole may increase the serum concentration of Proton Pump Inhibitors. Risk D: Consider therapy modification
Mesalamine: Proton Pump Inhibitors may diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Risk D: Consider therapy modification
Methotrexate: Proton Pump Inhibitors may decrease the excretion of Methotrexate. Antirheumatic doses of methotrexate probably hold minimal risk. Risk C: Monitor therapy
Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Nelfinavir: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Proton Pump Inhibitors may decrease the serum concentration of Nelfinavir. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Phenytoin: Proton Pump Inhibitors may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Risk X: Avoid combination
Raltegravir: Proton Pump Inhibitors may increase the serum concentration of Raltegravir. Risk C: Monitor therapy
Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Tacrolimus: Proton Pump Inhibitors may increase the serum concentration of Tacrolimus. Management: Tacrolimus dose adjustment may be required. Rabeprazole, pantoprazole, or selected H2-receptor antagonists (i.e., ranitidine or famotidine) may be less likely to interact. Genetic testing may predict patients at highest risk. Risk D: Consider therapy modification
Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Omeprazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may cause gastric mucosal irritation).
Food: Food delays absorption.
Storage
Capsules, tablets: Store at 15°C to 30°C (59°F to 86°F). Protect from light and moisture.
Granules for oral suspension: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Reconstitution
Granules for oral suspension: For oral administration, empty the contents of the 2.5 mg packet into 5 mL of water (10 mg packet into 15 mL of water); stir. For NG administration, add 5 mL of water into a catheter-tipped syringe, and then add the contents of a 2.5 mg packet (15 mL water for the 10 mg packet); shake. Note: Regardless of the route of administration, the suspension should be left to thicken for 2-3 minutes prior to administration.
Mechanism of Action
Proton pump inhibitor; suppresses gastric basal and stimulated acid secretion by inhibiting the parietal cell H+/K+ ATP pump
Pharmacodynamics/Kinetics
Onset of action: Antisecretory: ~1 hour
Peak effect: Within 2 hours
Duration: Up to 72 hours; 50% of maximum effect at 24 hours; after stopping treatment, secretory activity gradually returns over 3-5 days
Absorption: Rapid
Protein binding: ~95%
Metabolism: Extensively hepatic by cytochrome P450 system to inactive metabolites; saturable first-pass effect
Bioavailability: Oral: ~30% to 40%; increased in Asian patients, elderly patients, and patients with hepatic dysfunction
Half-life elimination: 0.5-1 hour; hepatic impairment: ~3 hours
Time to peak, plasma: 0.5-3.5 hours
Excretion: Urine (~77% as metabolites, very small amount as unchanged drug); feces
Dosage
Oral:
Children 1-16 years: GERD or other acid-related disorders:
5 kg to <10 kg: 5 mg once daily
10 kg to <20 kg: 10 mg once daily
?20 kg: 20 mg once daily
Adults:
Active duodenal ulcer: 20 mg/day for 4-8 weeks
Gastric ulcers: 40 mg/day for 4-8 weeks
Symptomatic GERD (without esophageal lesions): 20 mg/day for up to 4 weeks
Erosive esophagitis: 20 mg/day for 4-8 weeks; maintenance of healing: 20 mg/day for up to 12 months total therapy (including treatment period of 4-8 weeks)
Helicobacter pylori eradication: Dose varies with regimen:
Manufacturer labeling: 40 mg once daily administered with clarithromycin 500 mg 3 times/day for 14 days or 20 mg twice daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10 days. Note: Presence of ulcer at time of therapy initiation may necessitate an additional 14-18 days of omeprazole 20 mg/day (monotherapy) after completion of combination therapy.
American College of Gastroenterology guidelines (Chey, 2007):
Nonpenicillin allergy: 20 mg twice daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10-14 days
Penicillin allergy: 20 mg twice daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10-14 days or 20 mg once or twice daily administered with bismuth subsalicylate 525 mg and metronidazole 250 mg plus tetracycline 500 mg 4 times/day for 10-14 days
Pathological hypersecretory conditions: Initial: 60 mg once daily; doses up to 120 mg 3 times/day have been administered; administer daily doses >80 mg in divided doses
Stress-ulcer prophylaxis (ICU patients; unlabeled use): 40 mg once daily; periodically evaluate patient for continued need.
Frequent heartburn (OTC labeling): 20 mg/day for 14 days; treatment may be repeated after 4 months if needed
Dosage adjustment in hepatic impairment: Bioavailability is increased with chronic liver disease. Consider dosage adjustment, especially for maintenance of erosive esophagitis. Specific guidelines are not available.
Administration: Oral
Best if administered before breakfast.
Capsule: Should be swallowed whole; do not chew or crush. Delayed release capsule may be opened and contents added to 1 tablespoon of applesauce (use immediately after adding to applesauce).
Oral suspension: Following reconstitution, the suspension should be left to thicken for 2-3 minutes and administered within 30 minutes. If any material remains after administration, add more water, stir, and administer immediately.
Tablet: Should be swallowed whole; do not crush or chew.
Administration: Other
Nasogastric tube administration:
Capsule: When using capsules to extemporaneously prepare a solution for NG administration, the manufacturers of Prilosec® recommend the use of an acidic juice for preparation and administration
Oral suspension: Following reconstitution in a catheter-tipped syringe, shake the suspension well and leave to thicken for 2-3 minutes. Administer within 30 minutes of reconstitution. Use an NG tube or gastric tube that is a French size 6 or larger; flush the syringe and tube with water.
Dietary Considerations
Should be taken on an empty stomach; best if taken before breakfast.
Patient Education
Take as directed, before eating. Do not crush or chew capsules. Delayed release capsule may be opened and contents added to applesauce. Avoid alcohol. You may experience anorexia; small frequent meals may help to maintain adequate nutrition. Report severe headache, unresolved severe diarrhea, or abdominal pain. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
In clinical trials, the incidence of side effects in the elderly is no different than that of younger adults (?65 years) despite slight decrease in elimination and increase in bioavailability. Bioavailability may be increased in the elderly (?65 years of age), however, dosage adjustments are not necessary.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: A 2 mg/mL oral omeprazole solution (Simplified Omeprazole Solution) can be prepared with five omeprazole 20 mg delayed release capsules and 50 mL 8.4% sodium bicarbonate. Empty capsules into beaker. Add sodium bicarbonate solution. Gently stir (about 15 minutes) until a white suspension is formed. Transfer to amber-colored syringe or bottle. Stable for 14 days at room temperature or for 30 days under refrigeration.
DiGiancinto JL, Olsen KM, Bergman KL, et al, “Stability of Suspension Formulations of Lansoprazole and Omeprazole Stored in Amber-Colored Plastic Oral Syringes,” Ann Pharmacother, 2000, 34:600-5.
Quercia R, Fan C, Liu X, et al, “Stability of Omeprazole in an Extemporaneously Prepared Oral Liquid,” Am J Health Syst Pharm, 1997, 54:1833-6.
Sharma V, “Comparison of 24-Hour Intragastric pH Using Four Liquid Formulations of Lansoprazole and Omeprazole,” Am J Health Syst Pharm, 1999, 56(Suppl 4):S18-21.
Evidence-Based Information: The 2008 Surviving Sepsis Campaign guidelines recommend that stress ulcer prophylaxis using an H2 blocker (Grade 1A) or proton pump inhibitor (Grade 1B) be given to patients with severe sepsis to prevent upper GI bleed. Benefit of prevention of upper GI bleed must be weighed against potential effect of increased stomach pH on development of ventilator-associated pneumonia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Taste perversion, dry mouth, esophageal candidiasis, and mucosal atrophy (tongue).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness, agitation, aggression, depression, confusion, insomnia, nervousness, anxiety, or hallucinations; may rarely cause sedation
Mental Health: Effects on Psychiatric Treatment
May inhibit the metabolism of diazepam; monitor for increased sedation
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions (especially those dependent on cytochrome P450 metabolism or those dependent on a acid environment for absorption). Monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically throughout therapy. Assess knowledge/teach appropriate use of this medication, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release: 10 mg, 20 mg, 40 mg
Prilosec®: 10 mg, 20 mg, 40 mg
Granules for suspension, delayed release, enteric coated, oral:
Prilosec®: 2.5 mg/packet (30s); 10 mg/packet (30s)
Tablet, delayed release: 20 mg
Prilosec OTC™: 20 mg
Pricing: U.S. (www.drugstore.com)
Capsule, delayed release (Omeprazole)
10 mg (30): $32.99
20 mg (90): $79.97
40 mg (30): $170.01
Capsule, delayed release (PriLOSEC)
20 mg (30): $459.99
40 mg (30): $250.37
Tablet, EC (Omeprazole)
20 mg (28): $25.99
Tablet, EC (PriLOSEC OTC)
20 mg (14): $19.99
Extemporaneously Prepared
A 2 mg/mL oral omeprazole solution (Simplified Omeprazole Solution) can be prepared with five omeprazole 20 mg delayed release capsules and 50 mL 8.4% sodium bicarbonate. Empty capsules into beaker. Add sodium bicarbonate solution. Gently stir (about 15 minutes) until a white suspension is formed. Transfer to amber-colored syringe or bottle. Stable for 14 days at room temperature or for 30 days under refrigeration.
DiGiancinto JL, Olsen KM, Bergman KL, et al, “Stability of Suspension Formulations of Lansoprazole and Omeprazole Stored in Amber-Colored Plastic Oral Syringes,” Ann Pharmacother, 2000, 34:600-5.
Quercia R, Fan C, Liu X, et al, “Stability of Omeprazole in an Extemporaneously Prepared Oral Liquid,” Am J Health Syst Pharm, 1997, 54:1833-6.
Sharma V, “Comparison of 24-hour Intragastric pH Using Four Liquid Formulations of Lansoprazole and Omeprazole,” Am J Health Syst Pharm, 1999, 56(Suppl 4):S18-21.
Extemporaneous preparation for NG administration (Prilosec®): The manufacturer recommends the use of an acidic juice for preparation to administer via nasogastric (NG) tube. Alternative methods have been described as follows. NG tube administration for the prevention of stress-related mucosal damage in ventilated, critically-ill patients. The manufacturer makes no judgment regarding the safety or efficacy of these practices.
The contents of one or two 20 mg omeprazole delayed release capsules were poured into a syringe; 10-20 mL of an 8.4% sodium bicarbonate solution was withdrawn in the syringe; 30 minutes were allowed for the enteric-coated omeprazole granules to break down. The resulting milky substance was shaken prior to administration. The NG tube was then flushed with 5-10 mL of water and then clamped for at least 1 hour. Patients received omeprazole 40 mg once, then 40 mg 6-8 hours later, then 20 mg once daily using this technique.
Another study used a different technique. The omeprazole delayed release capsule (20 mg or 40 mg) was opened; then the intact granules were poured into a container holding 30 mL of water. With the plunger removed, 1/3 to 1/2 of the granules were then poured into a 30 mL syringe which was attached to a nasogastric tube (NG). The plunger was replaced with 1 cm of air between the granules and the plunger top while the plunger was depressed. This process was repeated until all the granules were flushed, then a final 15 mL of water was flushed through the tube. Patients who received omeprazole 40 mg in this manner had a more predictable increase in intragastric pH than patients who received omeprazole 20 mg.
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International Brand Names
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Last full review/revision November 2009
Content last modified November 2009
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