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Special Alerts
Possible Increased Risk of Fractures (Hip, Wrist, and Spine) with Proton Pump Inhibitor (PPI) Use (Update)
March 2011
The U.S. Food and Drug Administration (FDA) has announced that over-the-counter (OTC) labeling for proton pump inhibitors (PPI) will not be required to carry an osteoporosis or fracture warning at this time. In May 2010, the FDA had revised all prescription and OTC labels for PPIs with information regarding an increase in the risk of fractures (hip, wrist, and spine) based on several epidemiologic studies. The greatest risk for these fractures was in patients who received high doses or used them for ≥1 year. The majority of the patients in the epidemiologic studies were ≥50 years of age with the risk of fractures being limited to this age group. The FDA has now concluded that short-term, low dose PPI use is unlikely to increase fracture risk.
The FDA has recommended that healthcare providers continue to prescribe, and patients continue to use these products as described within their labeling. In addition, healthcare providers should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. Patients who continue to receive PPIs and who are at risk for osteoporosis, should receive vitamin D and calcium supplementation and have their bone status monitored and managed according to current practice standards. Patients should not stop taking their proton pump inhibitor unless told to do so by their healthcare provider.
For more information, U.S. healthcare professionals may refer to the following websites:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213321.htm
Proton Pump Inhibitors (PPIs): Long-term Use May be Associated With Hypomagnesemia
March 2011
The U.S. Food and Drug Administration (FDA) is notifying healthcare providers and patients that long-term use of proton pump inhibitors (PPIs) may be associated with hypomagnesemia. Some of the reported cases of hypomagnesemia occurred after 3 months of use, but most occurred in patients using PPIs for longer than 1 year. The mechanism for this adverse effect is not clearly defined.
Healthcare providers should consider obtaining serum magnesium levels prior to beginning long-term PPI therapy, especially in patients taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Although magnesium supplementation may correct hypomagnesemia, discontinuation of the PPI may be necessary to correct and maintain normal magnesium levels. Typically, according to the case reports, magnesium levels returned to normal within 1 week of stopping the PPI. Hypomagnesemia can cause serious adverse events including tetany, tremors, seizures, QT prolongation, and cardiac arrhythmias. Patients should not stop PPI therapy without first discussing with a healthcare professional.
The FDA is requiring all manufacturers of prescription PPI products to update the package labeling to include the potential risk of hypomagnesemia. Since OTC PPIs are only approved for short-term use, the package labeling for these products will not be updated. However, healthcare professionals should be aware of the risk of hypomagnesemia if OTC PPIs are used longer than the approved use.
For additional information, please refer to http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm.
Statement Released Regarding Clopidogrel-Proton Pump Inhibitor (PPI) Interaction
November 2010
The American College of Cardiology Foundation, in conjunction with the American College of Gastroenterology and the American Heart Association, has issued a consensus document regarding the concomitant use of PPIs and thienopyridines, specifically clopidogrel.
The following highlighted recommendations are discussed within this consensus statement:
- Clopidogrel alone, aspirin alone, and their combination are associated with an increased risk of GI bleeding.
- Risk of GI bleeding increases as the number of risk factors increase (eg, prior GI bleeding, advanced age, concurrent use of anticoagulants).
- PPIs are appropriate in patients with multiple risk factors for GI bleeding who are also receiving antiplatelet therapy (eg, clopidogrel).
- Although pharmacokinetic and pharmacodynamic studies have demonstrated varying effects of PPIs on the extent of clopidogrel metabolic conversion to the active metabolite, no evidence has established clinically meaningful differences in outcomes.
- A clinically-significant interaction cannot be excluded in subgroups who are poor metabolizers of clopidogrel.
- Until solid evidence exists to support staggering PPIs with clopidogrel, the dosing of PPIs should not be altered.
Healthcare professionals must evaluate the risks and benefits of concomitant use of PPIs and thienopyridines, considering both the cardiovascular and GI complications. For more information, healthcare professionals may refer to the following website: http://content.onlinejacc.org/cgi/reprint/j.jacc.2010.09.010v1.pdf
Pronunciation
(es oh ME pray zol)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Short-term (4-8 weeks) treatment of erosive esophagitis; maintaining symptom resolution and healing of erosive esophagitis; treatment of symptomatic gastroesophageal reflux disease (GERD); as part of a multidrug regimen for Helicobacter pylori eradication in patients with duodenal ulcer disease (active or history of within the past 5 years); prevention of gastric ulcers in patients at risk (age ≥60 years and/or history of gastric ulcer) associated with continuous NSAID therapy; long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome
Canadian labeling: Additional use (not in U.S. labeling): Oral: Treatment of nonerosive reflux disease (NERD)
I.V.: Short-term (≤10 days) treatment of gastroesophageal reflux disease (GERD) when oral therapy is not possible or appropriate
Use: Unlabeled/Investigational
I.V.: Prevention of recurrent peptic ulcer bleeding postendoscopy
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. However, there are no adequate and well-controlled studies in pregnant women. Congenital abnormalities have been reported sporadically following omeprazole use during pregnancy.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Esomeprazole excretion into breast milk has not been studied. However, omeprazole is excreted in breast milk, and therefore considered likely that esomeprazole is similarly excreted; breast-feeding is not recommended.
Contraindications
Hypersensitivity to esomeprazole, substituted benzimidazoles (eg, omeprazole, 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); this may also occur with esomeprazole.
• Carcinoma: No reports of enterochromaffin-like (ECL) cell carcinoids, dysplasia, or neoplasia have occurred.
• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor therapy. Patients on high-dose or long-term 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.
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: Patients with severe liver dysfunction may require dosage reductions.
Concurrent drug therapy issues:
• Clopidogrel: Proton pump inhibitors may diminish the therapeutic effect of clopidogrel thought to be due to reduced formation of the active metabolite of clopidogrel; an increase in the risk of cardiovascular events may occur. The manufacturer of clopidogrel recommends avoidance of concomitant administration of another PPI (ie, omeprazole); similar recommendations with esomeprazole would appear prudent.
Special populations:
• Asian ethnicity: Bioavailability may be increased in patients of Asian descent.
• Elderly: Bioavailability may be increased in the elderly.
Dosage form specific issues:
• Intravenous: Safety and efficacy of I.V. treatment beyond 10 days have not been established; transition from I.V. to oral therapy as soon possible.
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).
Adverse Reactions
Unless otherwise specified, percentages represent adverse reactions identified in clinical trials evaluating the oral formulation.
>10%: Central nervous system: Headache (I.V. 11%; oral ≤8%)
1% to 10%:
Cardiovascular: Hypertension (≤3%), chest pain (>1%)
Central nervous system: Pain (4%), dizziness (oral >1%; I.V. 3%), anxiety (2%), insomnia (2%), pyrexia (2%), fatigue (>1%)
Dermatologic: Rash (>1%), pruritus (I.V. ≤1%)
Endocrine & metabolic: Hypercholesterolemia (2%)
Gastrointestinal: Flatulence (oral ≤5%; I.V. 10%), diarrhea (oral ≤7%; I.V. 4%), abdominal pain (oral ≤6%; I.V. 6%), nausea (oral 5%; I.V. 6%), dyspepsia (oral >1%; I.V. 6%), gastritis (≤6%), constipation (oral 2%; I.V. 3%), vomiting (≤3%), benign GI neoplasm (>1%), dyspepsia (>1%), duodenitis (>1%), epigastric pain (>1%), esophageal disorder (>1%), gastroenteritis (>1%), GI mucosal discoloration (>1%), serum gastrin increased (>1%), tooth disorder (>1%), xerostomia (1%)
Genitourinary: Urinary tract infection (4%)
Hematologic: Anemia (>1%)
Hepatic: Transaminases increased (>1%)
Local: Injection site reaction (I.V. 2%)
Neuromuscular & skeletal: Arthralgia (3%), back pain (>1%), fracture (>1%), arthropathy (1%), myalgia (1%)
Respiratory: Respiratory infection (oral ≤9%; I.V. 1%), bronchitis (4%), sinusitis (oral ≤4%; I.V. 2%), coughing (>1%), rhinitis (>1%), dyspnea (1%)
Miscellaneous: Accident/injury (≤8%), viral infection (4%), allergy (2%), ear infection (2%), hernia (>1%), flu-like syndrome (1%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abdominal rigidity, aggression, agitation, agranulocytosis, albuminuria, alkaline phosphatase increased, alopecia, anaphylactic reaction/shock, angioedema, anorexia, arthritis exacerbation, asthma exacerbation, benign polyps/nodules, bilirubinemia, blurred vision, bronchospasm, candidiasis (GI and genital), carcinoid tumor of stomach, cervical lymphadenopathy, conjunctivitis, cramps, creatinine increased, cystitis, dehydration, depression, dermatitis, dysmenorrhea, dysphagia, dysuria, edema (including facial, peripheral, and tongue), epigastric pain, epistaxis, erythema multiforme, esophageal varices, fibromyalgia syndrome, flushing, fungal infection, gastric retention, GI dysplasia, glycosuria, goiter, gynecomastia, hallucinations, hematuria, hepatic encephalopathy, hepatic failure, hepatitis, hyperhidrosis, hyperparathyroidism, hypertonia, hyperuricemia, hypoesthesia, hypokalemia, hypomagnesemia, hyponatremia, impotence, infusion site reaction (eg, erythema, edema), interstitial nephritis, jaundice, larynx edema, leukocytosis, leukopenia, malaise, micturition increased, migraine, muscular weakness, nervousness, osteoporosis, otitis media, pancreatitis, pancytopenia, paresthesia, pharyngolaryngeal pain, pharyngitis, phlebitis, photosensitivity, polymyalgia rheumatica, polyuria, proteinuria, pruritus ani, rhinorrhea, rigors, sleep disorder, somnolence, Stevens-Johnson syndrome, stomatitis, tachycardia, taste disturbances, thrombocytopenia, thrombophlebitis, thyroid-stimulating hormone increased, tinnitus, total bilirubin increased, toxic epidermal necrolysis, tremor, urticaria, vaginitis, vertigo, vitamin B12 deficiency, weight changes
Metabolism/Transport Effects
Substrate of CYP2C19 (major), 3A4 (major); Inhibits CYP2C19 (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
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
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: Esomeprazole may enhance the adverse/toxic effect of Cilostazol. Esomeprazole may increase the serum concentration of Cilostazol. Esomeprazole may increase the serum concentration of OPC-13015, an active metabolite of Cilostazol. Management: Monitor for increased cilostazol effects when coadministered with esomeprazole. The manufacturer recommends considering 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
Clopidogrel: Esomeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to the possible 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
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
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
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 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
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
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 decrease the excretion of Methotrexate. Antirheumatic doses of methotrexate probably hold minimal risk. 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
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
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
Vitamin K Antagonists (eg, warfarin): Esomeprazole 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
Food: Absorption is decreased by 43% to 53% when taken with food.
Storage
Capsule, granules: Store at 15°C to 30°C (59°F to 86°F). Keep container tightly closed.
Powder for injection: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Per the manufacturer, following reconstitution, solution for injection prepared in NS, and solution for infusion prepared in NS or LR should be used within 12 hours. Following reconstitution, solution for infusion prepared in D5W should be used within 6 hours. Refrigeration is not required following reconstitution.
Additional stability data: Following reconstitution, solutions for infusion prepared in D5W, NS, or LR in PVC bags are chemically and physically stable for 48 hours at room temperature (25°C) and for at least 120 hours under refrigeration (4°C) (Kupiec, 2008).
Reconstitution
Powder for injection:
For I.V. injection: Adults: Reconstitute powder with 5 mL NS.
For I.V. infusion:
Children: Initially reconstitute powder (20 mg or 40 mg) with 5 mL of NS, then further dilute to a final volume of 50 mL; withdraw the appropriate amount of the final solution to administer the intended dose.
Adults: Initially reconstitute powder with 5 mL of NS, LR, or D5W, then further dilute to a final volume of 50 mL.
Mechanism of Action
Proton pump inhibitor suppresses gastric acid secretion by inhibition of the H+/K+-ATPase in the gastric parietal cell. Esomeprazole is the S-isomer of omeprazole.
Pharmacodynamics/Kinetics
Distribution: Vdss: 16 L
Protein binding: 97%
Metabolism: Hepatic via CYP2C19 primarily and (to a lesser extent) via 3A4 to hydroxy, desmethyl, and sulfone metabolites (all inactive)
Bioavailability: Oral: 90% with repeat dosing
Half-life elimination: ~1-1.5 hours
Time to peak: Oral: 1.5-2 hours
Excretion: Urine (80%, primarily as inactive metabolites; <1% as active drug); feces (20%)
Dosage
Oral:
Children 1-11 years: Note: Safety and efficacy of doses >1 mg/kg/day and/or therapy beyond 8 weeks have not been established.
Symptomatic GERD: 10 mg once daily for up to 8 weeks
Erosive esophagitis (healing):
<20 kg: 10 mg once daily for 8 weeks
≥20 kg: 10-20 mg once daily for 8 weeks
Nonerosive reflux disease (NERD) (Canadian labeling): 10 mg once daily for up to 8 weeks
Adolescents 12-17 years:
GERD: 20-40 mg once daily for up to 8 weeks
NERD (Canadian labeling): 20 mg once daily for 2-4 weeks; lack of symptom control after 4 weeks warrants further evaluation
Adults:
Erosive esophagitis (healing): Initial: 20-40 mg once daily for 4-8 weeks; if incomplete healing, may continue for an additional 4-8 weeks; maintenance: 20 mg once daily (controlled studies did not extend beyond 6 months)
NERD (Canadian labeling): Initial: 20 mg once daily for 2-4 weeks; lack of symptom control after 4 weeks warrants further evaluation; maintenance (in patients with successful initial therapy): 20 mg once daily as needed
Symptomatic GERD: 20 mg once daily for 4 weeks; may continue an additional 4 weeks if symptoms persist
Helicobacter pylori eradication:
Manufacturer labeling: 40 mg once daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10 days
American College of Gastroenterology guidelines (Chey, 2007):
Nonpenicillin allergy: 40 mg once daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10-14 days
Penicillin allergy: 40 mg once daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10-14 days or 40 mg once daily administered with bismuth subsalicylate 525 mg and metronidazole 250 mg plus tetracycline 500 mg 4 times/day for 10-14 days
Canadian labeling: 20 mg twice daily for 7 days; requires combination therapy
Prevention of NSAID-induced gastric ulcers: 20-40 mg once daily for up to 6 months
Treatment of NSAID-induced gastric ulcers (Canadian labeling): 20 mg once daily for 4-8 weeks.
Pathological hypersecretory conditions (Zollinger-Ellison syndrome): 40 mg twice daily; adjust regimen to individual patient needs; doses up to 240 mg/day have been administered
I.V.:
Treatment of GERD (short-term): Note: Indicated only in cases where oral therapy is inappropriate or not possible; safety/efficacy ≥10 days has not been established.
Children 1-11 months: 0.5 mg/kg once daily
Children 1-17 years: <55 kg: 10 mg once daily; ≥55 kg: 20 mg once daily
Adults: 20 mg or 40 mg once daily
Prevention of recurrent peptic ulcer bleeding postendoscopy (unlabeled use; Sung, 2009): Adults: 80 mg over 30 minutes, followed by 8 mg/hour infusion for 72 hours, then 40 mg orally once daily for 27 additional days
Elderly: No dosage adjustment needed.
Dosage adjustment in renal impairment: No dosage adjustment needed
Dosage adjustment in hepatic impairment:
Safety and efficacy not established in children with hepatic impairment.
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment needed
Severe hepatic impairment (Child-Pugh class C): Dose should not exceed 20 mg/day
Administration: Oral
Capsule: Should be swallowed whole and taken at least 1 hour before eating (best if taken before breakfast). Capsule can be opened and contents mixed with 1 tablespoon of applesauce. Swallow immediately; mixture should not be chewed or warmed. For patients with difficulty swallowing, use of granules may be more appropriate.
Granules: Empty into container with 1 tablespoon of water and stir; leave 2-3 minutes to thicken. Stir and drink within 30 minutes. If any medicine remains after drinking, add more water, stir and drink immediately.
Tablet (Canadian formulation, not available in U.S.): Swallow whole or may be dispersed in a half a glass of noncarbonated water. Stir until tablets disintegrate, leaving a liquid containing pellets. Drink contents within 30 minutes. Do not chew or crush pellets. After drinking, rinse glass with water and drink.
Administration: I.V.
Flush line prior to and after administration with NS, LR, or D5W.
Children: Administer by intermittent infusion (10-30 minutes); the manufacturer recommends that children receive intravenous esomeprazole by intermittent infusion only.
Adults: May be administered by injection (≥3 minutes), intermittent infusion (10-30 minutes), or continuous infusion for up to 72 hours (Sung, 2009).
Administration: Other
Nasogastric tube:
Capsule: Open capsule and place intact granules into a 60 mL catheter-tip syringe; mix with 50 mL of water. Replace plunger and shake vigorously for 15 seconds. Ensure that no granules remain in syringe tip. Do not administer if pellets dissolve or disintegrate. Use immediately after preparation. After administration, flush nasogastric tube with additional water.
Granules: Delayed release oral suspension granules can also be given by nasogastric or gastric tube. Add 15 mL of water to a catheter-tip syringe, add granules from packet. Shake the syringe, leave 2-3 minutes to thicken. Shake the syringe and administer through nasogastric or gastric tube (size 6 French or greater) within 30 minutes. Refill the syringe with 15 mL of water, shake and flush nasogastric/gastric tube.
Tablet (Canadian formulation, not available in U.S.): Disperse tablets in 50 mL of noncarbonated water. Stir until tablets disintegrate leaving a liquid containing pellets. After administration, flush with additional 25-50 mL of water to clear the syringe and tube.
Administration: I.V. Detail
pH: 9-11
Monitoring Parameters
Susceptibility testing recommended in patients who fail H. pylori eradication regimen. Monitor for rebleeding in patients with peptic ulcer bleed.
Dietary Considerations
Take at least 1 hour before meals; best if taken before breakfast. The contents of the capsule may be mixed in applesauce or water; pellets also remain intact when exposed to orange juice, apple juice, and yogurt.
Patient Education
Take as directed, 1 hour before eating at same time each day. Swallow capsule whole; do not crush or chew. If you cannot swallow capsule whole, open capsule, mix contents with 1 tablespoon of applesauce, and swallow immediately; do not chew mixture. Do not store for future use. You may experience headache, constipation, diarrhea, or abdominal pain. Report persistent headache, diarrhea, abdominal pain, gas, changes in urination or pain on urination, or persistent muscular aches or pain.
Geriatric Considerations
Dose adjustment is 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:
Acute ulcer: Postendoscopy therapy: In a multicenter, double-blind trial conducted in 16 countries, 767 patients with peptic ulcer bleeding from a single gastric or duodenal source with high-risk features were randomized to intravenous esomeprazole (80 mg bolus over 30 minutes, followed by a continuous infusion of 8 mg/hour for a total of 72 hours) or placebo. After completion of intravenous therapy, all patients were administered oral esomeprazole 40 mg once daily for an additional 27 days. The use of intravenous esomeprazole demonstrated a significant reduction in the primary end point of clinically significant rebleeding within 72 hours (5.9% vs 10.3%, p=0.026). Although endoscopic therapy was not standardized, the efficacy of esomeprazole was not affected (Sung, 2009).
Intravenous omeprazole has also been studied in prevention of rebleeding in ulcer patients who are at high risk for rebleeding (endoscopic findings of active bleeding or nonbleeding visible vessel) after successful hemostasis (Lau, 2000; Lin, 1998).
Lin and his group treated 100 ulcer patients (actively bleeding ulcers or ulcers with nonbleeding visible vessels) endoscopically and then randomized them to cimetidine (300 mg bolus followed by 50 mg/hour infusion) or omeprazole (40 mg bolus, ~7 mg/hour infusion) for 72 hours. Patients were discharged on the oral form of the drug arm they were assigned to. The omeprazole group maintained an intragastric pH >6 for about 84% of the infusion duration, while the cimetidine group maintained their pH >6 only about 50% of the time. Rebleeding occurred significantly more often in the cimetidine group.
Lau and his colleagues treated patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels with an epinephrine infusion followed by thermocoagulation. They were then randomized to omeprazole (80 mg bolus followed by a continuous infusion of 8 mg/hour for 72 hours) or placebo. All patients were discharged on oral omeprazole (20 mg/day) for 8 weeks and received H. pylori treatment if indicated. The primary goal was to evaluate the rate of rebleeding during the first 30 days after endoscopy. Two hundred and forty patients were enrolled with randomization of 120 into each group. Bleeding recurred in significantly more patients receiving placebo than omeprazole infusion. The authors concluded that after endoscopic therapy, omeprazole reduces the risk of rebleeding in patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels.
Acute ulcer: Pre-endoscopy therapy: Lau and associates (2007) evaluated the effects of preemptive infusion of omeprazole before endoscopy in upper gastrointestinal bleeding. Consecutive patients (638) were stabilized and then randomly assigned to intravenous omeprazole (80 mg bolus followed by a continuous infusion of 8 mg/hour) or placebo infusion before endoscopy the next morning. The primary endpoint was the need for endoscopic therapy (eg, epinephrine, thermocoagulation). Seven patients were excluded from the analysis. The need for endoscopic treatment was significantly lower in the omeprazole group (60/314 patients; 19%) than in the placebo group (90/317; 28%). The active treatment group had a significantly shorter hospital stay. Duration of infusion before endoscopy was similar in both groups (~8-21 hours).
Stress ulcer prophylaxis: 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: Xerostomia (normal salivary flow resumes upon discontinuation)
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause headache
Mental Health: Effects on Psychiatric Treatment
The clearance of diazepam is decreased by 45% with concomitant use, resulting in increased diazepam levels and potential for toxicity; monitor
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking that are dependent on cytochrome P450 metabolism or on an acid environment for absorption.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release, oral, as magnesium [strength expressed as base]:
NexIUM®: 20 mg, 40 mg
Granules for suspension, delayed release, oral, as magnesium [strength expressed as base]:
NexIUM®: 10 mg/packet (30s); 20 mg/packet (30s); 40 mg/packet (30s)
Injection, powder for reconstitution, as sodium [strength expressed as base]:
NexIUM® I.V.: 20 mg, 40 mg [contains edetate disodium]
Pricing: U.S. (www.drugstore.com)
Capsule, delayed release (NexIUM)
20 mg (30): $200.99
40 mg (30): $182.99
References
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Lau JY, Sung JJ, Lee KK, et al, “Effect of Intravenous Omeprazole on Recurrent Bleeding After Endoscopic Treatment of Bleeding Peptic Ulcers,” N Engl J Med, 2000, 343(5):310-6.
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Li X-Q, Anderson TB, Ahlstrom M, et al, “Comparison of Inhibitory Effects of the Proton Pump-Inhibiting Drugs Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, and Rabeprazole on Human Cytochrome P450 Activities,” Drug Metab Disp, 2004, 32(8):821-7.
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Sung JJ, Barkun A, Kuipers EJ, et al, “Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial,” Ann Intern Med, 2009, 150(7):455-64.
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Wolfe MM and Sachs G, “Acid Suppression: Optimizing Therapy for Gastroduodenal Ulcer Healing, Gastroesophageal Reflux Disease, and Stress-Related Erosive Syndrome,” Gastroenterology, 2000,118(2 Suppl 1):9-31.
Zhao J, Li J, Hamer-Maansson JE, et al, “Pharmacokinetic Properties of Esomeprazole in Children Aged 1 to 11 Years With Symptoms of Gastroesophageal Reflux Disease: A Randomized, Open-Label Study,” Clin Ther, 2006, 28(11): 1868-76.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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