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Special Alerts
Possible Increased Risk of Clostridium Difficile–Associated Diarrhea (CDAD) with Proton Pump Inhibitor Use: Update
February 2012
The U.S. Food and Drug Administration (FDA) and Health Canada have announced that proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD). The FDA reviewed reports of PPI-associated CDAD from the FDA Adverse Event Reporting System and from the medical literature. The association of PPI use and CDAD varied among studies, ranging from a risk of 1.4-2.75 higher in those exposed to a PPI compared to those without PPI exposure. Many of the cases reported involved patients who were elderly, had chronic and/or underlying conditions, or were taking broad-spectrum antibiotics - all of which could have increased the risk of CDAD. Health Canada has also been assessing study data on an ongoing basis. In spite of potential predisposition to CDAD, or other limitations to study design, association with PPI use could not be ruled out and patients with these risk factors may have more serious outcomes from CDAD associated with PPI use. The FDA is working with manufacturers to include information regarding the increased risk of CDAD with use of PPIs in their prescribing information and is also evaluating the risk of CDAD in users of histamine H2 receptor blockers. Health Canada also notes that the possible association between PPIs and CDAD is noted in their PPI product labeling.
The following advice is provided by the FDA and Health Canada to assist healthcare professionals in the management of patients receiving PPIs:
- Consider a diagnosis of CDAD in PPI users that have persistent diarrhea.
- Advise patients to get immediate care from a healthcare professional if they experience persistent watery stools, bloody diarrhea, abdominal pain or tenderness, nausea, loss of appetite, or fever while taking PPIs.
- Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.
For more information, refer to the following websites:
U.S.:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm
Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2012/2012_23-eng.php
Pronunciation
(oh MEP ra zole)
Generic Available (U.S.)
Yes: Excludes granules for suspension
Index Terms
Brand Names: U.S.
Brand Names: Canada
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
Healing NSAID-induced ulcers; prevention of NSAID-induced ulcer; stress-ulcer prophylaxis in the critically-ill
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies. 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
Breast-Feeding Considerations
Following administration of omeprazole 20 mg, peak concentrations detected in the breast milk were <7% of the maternal serum concentration.
Contraindications
Hypersensitivity to omeprazole, substituted benzimidazoles (eg, esomeprazole, lansoprazole), or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Atrophic gastritis: Long-term omeprazole therapy has caused atrophic gastritis (identified 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.
• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose (multiple daily doses)or long-term (≥1 year) therapy should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.
• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of >3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of omeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.
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.
Concurrent drug therapy issues:
• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of omeprazole (even when scheduled 12 hours apart) or use of a PPI with less potent CYP2C19 inhibition (eg, pantoprazole). Others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically-significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham, 2010; Levine, 2011).
• CYP3A4 or 2C19 inducers (eg, St John's wort, rifampin): May decrease the therapeutic efficacy of omeprazole; concurrent use not recommended.
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.
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).
• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; May cause false positive results in diagnostic investigations for neuroendocrine tumors. Stop omeprazole treatment temporarily before CgA test; If CgA level high repeat to confirm. Use same commercial lab for testing to prevent variable results.
• 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 (7%), dizziness (2%)
Dermatologic: Rash (2%)
Gastrointestinal: Abdominal pain (5%), diarrhea (4%), nausea (4%), vomiting (3%), flatulence (3%), acid regurgitation (2%), constipation (2%)
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, anaphylaxis, anemia, angina, angioedema, anorexia, anxiety, apathy, AST increased, atrophic gastritis, benign gastric polyps, bilirubin increased, blurred vision, bradycardia, bronchospasm, chest pain, cholestatic hepatitis, confusion, creatinine increased, depression, double vision, dry skin, epistaxis, erythema multiforme, esophageal candidiasis, fatigue, fecal discoloration, fever, fracture, gastroduodenal carcinoids, GGT increased, glycosuria, gynecomastia, hallucinations, hematuria, hemolytic anemia, hepatic encephalopathy, hepatic failure, hepatic necrosis, hepatitis, hepatocellular hepatitis, hyperhidrosis, hypersensitivity, hypertension, hypoglycemia, hypomagnesemia, 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), osteoporosis-related fracture, pain, palpitation, pancreatitis, pancytopenia, paresthesia, peripheral edema, petechiae, pharyngeal pain, photosensitivity, proteinuria, pruritus, psychiatric disturbance, purpura, skin inflammation, sleep disturbance, somnolence, Stevens-Johnson syndrome, stomatitis, tachycardia, taste perversion, 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), CYP2C19 (major), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP2C19 (moderate), CYP2C9 (moderate), CYP2D6 (weak), CYP3A4 (weak); Induces CYP1A2 (weak/moderate)
Drug Interactions
Amphetamines: Proton Pump Inhibitors may increase the serum concentration of Amphetamines. Specifically, data indicate that Proton Pump Inhibitors may increase the rate at which Amphetamines are absorbed. Total exposure to Amphetamines is not significantly changed. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: Avoid concurrent PPI in HIV treatment-experienced patients. For treatment-naive patients, atazanavir/ritonavir dose should be given approximately 12 hours after the PPI, and the PPI should not exceed the equivalent of 20 mg omeprazole. 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
Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. 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
Cefditoren: Proton Pump Inhibitors may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Risk D: Consider therapy modification
Cilostazol: Omeprazole may enhance the adverse/toxic effect of Cilostazol. Omeprazole may increase the serum concentration of Cilostazol. Omeprazole may increase the serum concentration of OPC-13015, an active metabolite of Cilostazol. Management: Monitor for increased effects of cilostazol when coadministered with omeprazole. Consider a 50% dose reduction of cilostazol (eg, 100 mg twice daily to 50 mg twice daily) with concomitant use of these agents. Risk D: Consider therapy modification
Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification
Clopidogrel: Omeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk X: Avoid combination
CloZAPine: Omeprazole may decrease the serum concentration of CloZAPine. Omeprazole may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CycloSPORINE: Omeprazole may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Omeprazole may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
Dabigatran Etexilate: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Avoid concurrent use of proton pump inhibitors with dasatinib. Antacids (taken 2 hours before or after dasatinib administration) should be used in place of these agents if some acid-reducing therapy is needed. 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
Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy
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
Fosphenytoin: Proton Pump Inhibitors may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. 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
Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) 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 increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. 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
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
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
Rifampin: May decrease the serum concentration of Omeprazole. Risk X: Avoid combination
Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
St Johns Wort: May decrease the serum concentration of Omeprazole. Risk X: Avoid combination
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
Tacrolimus (Systemic): Proton Pump Inhibitors may increase the serum concentration of Tacrolimus (Systemic). 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
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Vismodegib: Proton Pump Inhibitors may decrease the serum concentration of Vismodegib. Management: Carefully consider the need for any medication that increases the pH of the upper GI tract (PPIs, H2RAs, antacids), as these could significantly reduce vismodegib systemic exposure. Vismodegib dose increases are unlikely to compensate for this effect. Risk D: Consider therapy modification
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.
Herb/Nutraceutical: Avoid use of St John's wort (may decrease efficacy of omeprazole).
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: Hepatic via CYP2C19 primarily and (to a lesser extent) via 3A4 to hydroxy, desmethyl, and sulfone metabolites (all inactive); 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 once daily for 4-8 weeks
Gastric ulcers: 40 mg once daily for 4-8 weeks
Symptomatic GERD (without esophageal lesions): 20 mg once daily for up to 4 weeks
Erosive esophagitis: 20 mg once daily for 4-8 weeks; maintenance of healing: 20 mg once daily 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 (Levy, 1997)
Frequent heartburn (OTC labeling): 20 mg once daily 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); mixture should not be chewed or warmed.
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/orogastric (NG/OG) tube administration:
Capsule: When using capsules to extemporaneously prepare a solution for NG/OG administration, the manufacturers of Prilosec® recommend the use of an acidic juice for preparation and administration. Alternative methods have been described as follows:
NG/OG tube administration for the prevention of stress-related mucosal damage in ventilated, critically-ill patients:
Study 1 (Phillips, 1996): Pour the contents of one or two 20 mg omeprazole delayed release capsules (depending on the dose) into a syringe (after removing plunger); withdraw 10-20 mL of an 8.4% sodium bicarbonate solution into the syringe; allow 30 minutes for the enteric-coated omeprazole granules to break down. Shake the resulting milky substance prior to administration. Flush the NG tube with 5-10 mL of water and clamp for at least 1 hour.
Study 2 (Balaban, 1997): Open the omeprazole delayed release capsule (20 mg or 40 mg), then pour the intact granules into a container holding 30 mL of water. Pour one-third to one-half of the granules into a 30 mL syringe (with the plunger removed) attached to a nasogastric tube (NG). Replace the plunger with 1 cm of air between the granules and the plunger top while the plunger is depressed. Repeat this process until all the granules are flushed, then flush a final 15 mL of water through the tube.
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 size 6 French or larger; flush the syringe and tube with water.
Monitoring Parameters
Susceptibility testing is recommended in patients who fail H. pylori-eradication regimen.
Test Interactions
Omeprazole may falsely elevate serum chromogranin A (CgA) levels. The increased CgA level may cause false-positive results in the diagnosis of a neuroendocrine tumor. Temporarily stop omeprazole if assessing CgA level; repeat level if initially elevated; use the same laboratory for all testing of CgA levels.
Dietary Considerations
Should be taken on an empty stomach; best if taken before breakfast.
Patient Education
Take 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.
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.
An increased risk of fractures of the hip, spine, or wrist has been observed in epidemiologic studies with proton pump inhibitor (PPI) use, primarily in older adults ≥50 years of age. The greatest risk was seen in patients receiving high doses or on long-term therapy (≥1 year). Calcium and vitamin D supplementation and close monitoring are recommended to reduce the risk of fracture in high-risk patients.
Anesthesia and Critical Care Concerns/Other Considerations
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
For patients at risk of osteoporosis-related fractures, optimize preventive measures and limit high-dose, prolonged therapy if possible.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release, oral: 10 mg, 20 mg, 40 mg
PriLOSEC®: 10 mg, 20 mg, 40 mg
Granules for suspension, delayed release, oral:
PriLOSEC®: 2.5 mg/packet (30s); 10 mg/packet (30s)
Powder for suspension, oral [compounding kit]:
First®-Omeprazole: 2 mg/mL (90 mL, 150 mL, 300 mL) [contains benzyl alcohol]
Tablet, delayed release, oral: 20 mg
PriLOSEC OTC®: 20 mg
Pricing: U.S. (www.drugstore.com)
Capsule, delayed release (Omeprazole)
10 mg (30): $34.99
20 mg (90): $99.97
40 mg (30): $195.00
Capsule, delayed release (PriLOSEC)
10 mg (30): $159.99
20 mg (30): $195.99
40 mg (30): $291.00
Tablet, EC (Omeprazole)
20 mg (14): $19.99
Tablet, EC (PriLOSEC OTC)
20 mg (14): $21.99
Extemporaneously Prepared
A 2 mg/mL oral omeprazole solution (Simplified Omeprazole Solution) may be made with five omeprazole 20 mg delayed release capsules and 50 mL sodium bicarbonate 8.4%. Empty capsules into beaker. Add sodium bicarbonate solution. Gently stir (about 15 minutes) until a white suspension forms. Transfer to amber-colored syringe or bottle. Stable for 14 days at room temperature or for 30 days refrigerated.
DiGiacinto 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(5):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(16):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(23 Suppl 4):18-21.
References
Abraham NS, Hlatky MA, Antman EM, et al, “ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents,” Circulation, 2010, 122(24):2619-33.
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International Brand Names
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Last full review/revision March 2012
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