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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
(pan TOE pra zole)
Generic Available (U.S.)
Yes: Delayed release tablet
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Treatment and maintenance of healing of erosive esophagitis associated with GERD; reduction in relapse rates of daytime and nighttime heartburn symptoms in GERD; hypersecretory disorders associated with Zollinger-Ellison syndrome or other GI hypersecretory disorders
I.V.: Short-term treatment (7-10 days) of patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis; hypersecretory disorders associated with Zollinger-Ellison syndrome or other neoplastic disorders
Use: Unlabeled/Investigational
Peptic ulcer disease, active ulcer bleeding (parenteral formulation); adjunct treatment with antibiotics for Helicobacter pylori eradication; stress-ulcer prophylaxis in the critically-ill
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only if clearly needed.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Not recommended due to carcinogenicity in animal studies.
Contraindications
Hypersensitivity to pantoprazole, substituted benzamidazoles (eg, esomeprazole, lansoprazole, omeprazole, rabeprazole), or any component of the formulation
Canadian labeling: Additional contraindication (not in U.S. labeling): Concomitant use with atazanavir
Warnings/Precautions
Concerns related to adverse effects:
• Atrophic gastritis: Long-term pantoprazole therapy (especially in patients who were H. pylori positive) has caused biopsy-proven atrophic gastritis.
• Carcinoma: No occurrences of enterochromaffin-like (ECL) cell carcinoids, dysplasia, or neoplasia, such as those seen in rodent studies, have been reported in humans.
• 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.
• Vitamin B12 malabsorption: Prolonged treatment (typically >3 years) may lead to vitamin B12 malabsorption and subsequent deficiency.
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.
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. Of the PPIs, pantoprazole has the lowest degree of CYP2C19 inhibition and is preferred if concomitant use of a PPI is necessary.
Dosage form specific issues:
• Edetate sodium (EDTA): Intravenous preparation contains edetate sodium; use caution in patients who are at risk for zinc deficiency if other EDTA-containing solutions are coadministered.
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
≥1%:
Cardiovascular: Chest pain
Central nervous system: Headache (2% to 9%), insomnia (≤1%), anxiety, dizziness, migraine
Dermatologic: Rash (≤2%)
Endocrine & metabolic: Hyperglycemia (≤1%), hyperlipidemia
Gastrointestinal: Diarrhea (2% to 6%), flatulence (2% to 4%), abdominal pain (1% to 4%), nausea (≤2%), vomiting (≤2%), eructation (≤1%), constipation, dyspepsia, gastroenteritis, rectal disorder
Genitourinary: Urinary frequency, UTI
Hepatic: Liver function tests abnormal (≤2%)
Local: Injection site reaction (includes thrombophlebitis and abscess)
Neuromuscular & skeletal: Arthralgia, back pain, hypertonia, neck pain, weakness
Respiratory: Bronchitis, cough, dyspnea, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection
Miscellaneous: Flu syndrome, infection, pain
<1%, postmarketing, and/or case reports: Abnormal dreams, acne, albuminuria, alkaline phosphatase increased, allergic reaction, alopecia, anaphylaxis, anemia, angioedema, angina pectoris, anorexia, aphthous stomatitis, appetite increased, arrhythmia, asthma exacerbation, atrial fibrillation/flutter, atrophic gastritis, balanitis, biliary pain, blurred vision, bone pain, breast pain, bursitis, cataract, CHF, chills, cholecystitis, cholelithiasis, CPK increased, colitis, confusion, contact dermatitis, creatinine increased, cystitis, deafness, decreased reflexes, dehydration, depression, diabetes mellitus, diaphoresis, diplopia, duodenitis, dysarthria, dysmenorrhea, dysphagia, dysuria, ecchymosis, ECG abnormality, eczema, eosinophilia, epididymitis, epistaxis, erythema multiforme, esophagitis, extraocular palsy, facial edema, fever, fracture, fungal dermatitis, gastrointestinal carcinoma, gastrointestinal hemorrhage, gastrointestinal moniliasis, generalized edema, GGT increased, gingivitis, glaucoma, glossitis, glycosuria, goiter, gout, halitosis, hallucinations, heat stroke, hematemesis, hematuria, hemorrhage, hepatic failure, hepatitis, hernia, herpes simplex, herpes zoster, hiccup, hyperbilirubinemia, hyperesthesia, hyper-/hypotension, hyperkinesia, hyperuricemia, hypokinesia, impaired urination, impotence, interstitial nephritis, jaundice, kidney calculus, kidney pain, laryngitis, leg cramps, leukocytosis, leukopenia, libido decreased, lichenoid dermatitis, maculopapular rash, malaise, melena, mouth ulceration, myalgia, myocardial infarction, myocardial ischemia, neoplasm, nervousness, neuralgia, neuritis, nocturia, optic neuropathy (including anterior ischemic), otitis externa, palpitation, pancreatitis, pancytopenia, paresthesia, periodontal abscess, periodontitis, photosensitivity, pneumonia, pruritus, pyelonephritis, rectal hemorrhage, retinal vascular disorder, rhabdomyolysis, salivation increased, scrotal edema, seizure, skin ulcer, somnolence, Stevens-Johnson syndrome, stomach ulcer, stomatitis, syncope, tachycardia, taste perversion, tenosynovitis, thrombocytopenia, thrombosis, tinnitus, tongue discoloration, toxic epidermal necrolysis, tremor, urethral pain, urethritis, urticaria, vaginitis, vasodilation, vertigo, vision abnormal, weight changes, xerostomia
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), 2C19 (major), 2D6 (minor), 3A4 (minor); Inhibits CYP2C9 (weak), 2C19 (moderate), ABCG2; Induces CYP1A2 (weak), 3A4 (weak)
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
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
Clopidogrel: Pantoprazole 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
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. 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
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
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk D: Consider therapy modification
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).
Herb/Nutraceutical: Prolonged treatment (typically >3 years) may lead to vitamin B12 malabsorption and subsequent deficiency.
Storage
Oral: Store tablet and oral suspension at controlled room temperature of 20°C to 25°C (68°F to 77°F).
I.V.: Prior to reconstitution, store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. When reconstituted, solution is stable up to 96 hours at room temperature (Johnson, 2005). The preparation should be stored at 3°C to 5°C (37°F to 41°F) if it is stored beyond 48 hours to minimize discoloration. If further diluting in 100 mL of D5W, LR, or NS, dilute within 6 hours of reconstitution. Diluted solution is stable at room temperature for up to 24 hours from the time of initial reconstitution; protection from light is not required.
Reconstitution
Reconstitute with 10 mL NS (final concentration 4 mg/mL). Reconstituted solution may be given intravenously (over 2 minutes) or may be added to 100 mL D5W, NS, or LR (for 15-minute infusion).
Compatibility
Stable in D5W, LR, NS.
Y-site administration: Incompatible: Midazolam, zinc.
Mechanism of Action
Suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump
Pharmacodynamics/Kinetics
Absorption: Rapid, well absorbed
Distribution: Vd: 11-24 L
Protein binding: 98%, primarily to albumin
Metabolism: Extensively hepatic; CYP2C19 (demethylation), CYP3A4; no evidence that metabolites have pharmacologic activity
Bioavailability: 77%
Half-life elimination: 1 hour; increased to 3.5-10 hours with CYP2C19 deficiency
Time to peak: Oral: 2.5 hours
Excretion: Urine (71%); feces (18%)
Dosage
Oral:
Children ≥5 years (unlabeled use): GERD, erosive esophagitis associated with GERD: 20-40 mg once daily
Adults:
Erosive esophagitis associated with GERD:
Treatment: 40 mg once daily for up to 8 weeks; an additional 8 weeks may be used in patients who have not healed after an 8-week course
Maintenance of healing: 40 mg once daily
Note: Lower doses (20 mg once daily) have been used successfully in mild GERD treatment and maintenance of healing
Hypersecretory disorders (including Zollinger-Ellison): Initial: 40 mg twice daily; adjust dose based on patient needs; doses up to 240 mg/day have been administered
Helicobacter pylori eradication (unlabeled use): American College of Gastroenterology guidelines (Chey, 2007):
Nonpenicillin allergy: 40 mg twice daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10-14 days
Penicillin allergy: 40 mg twice daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10-14 days or 40 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
I.V.:
Erosive esophagitis associated with GERD: 40 mg once daily for 7-10 days
Hypersecretory disorders: 80 mg twice daily; adjust dose based on acid output measurements; 160-240 mg/day in divided doses has been used for a limited period (up to 7 days)
Prevention of rebleeding in peptic ulcer bleed (unlabeled use): 80 mg, followed by 8 mg/hour infusion for 72 hours. Note: A daily infusion of 40 mg does not raise gastric pH sufficiently to enhance coagulation in active GI bleeds.
Elderly: Dosage adjustment not required
Dosage adjustment in renal impairment: Not required; pantoprazole is not removed by hemodialysis
Dosage adjustment in hepatic impairment: Not required
Administration: Oral
Tablet: Should be swallowed whole, do not crush or chew. Best if taken before breakfast.
Delayed-release oral suspension: Should only be administered in apple juice or applesauce and taken ~30 minutes before a meal. Do not administer with any other liquid (eg, water) or foods.
Oral administration in applesauce: Sprinkle intact granules on 1 tablespoon of applesauce and swallow within 10 minutes of preparation.
Oral administration in apple juice: Empty intact granules into 5 mL of apple juice (~1 teaspoonful), stir for 5 seconds, and swallow immediately after preparation. Rinse container once or twice with apple juice and swallow immediately.
Nasogastric tube administration: Separate the plunger from the barrel of a 60 mL catheter tip syringe and connect to a ≥16 French nasogastric tube. Holding the syringe attached to the tubing as high as possible, empty the contents of the packet into barrel of the syringe, add 10 mL of apple juice and gently tap/shake the barrel of the syringe to help empty the syringe. Add an additional 10 mL of apple juice and gently tap/shake the barrel to help rinse. Repeat rinse with at least 2-10 mL aliquots of apple juice. No granules should remain in the syringe.
Administration: I.V.
Flush I.V. line before and after administration. In-line filter not required.
2-minute infusion: The volume of reconstituted solution (4 mg/mL) to be injected may be administered intravenously over at least 2 minutes.
15-minute infusion: Infuse over 15 minutes at a rate not to exceed 7 mL/minute (3 mg/minute).
Monitoring Parameters
Hypersecretory disorders: Acid output measurements, target level <10 mEq/hour (<5 mEq/hour if prior gastric acid-reducing surgery)
Test Interactions
False-positive urine screening tests for tetrahydrocannabinol (THC) have been noted in patients receiving proton pump inhibitors, including pantoprazole.
Dietary Considerations
Oral: May be taken with or without food; best if taken before breakfast.
I.V.: Due to EDTA in preparation, zinc supplementation may be needed in patients prone to zinc deficiency.
Patient Education
Take at similar time each day. Swallow tablet whole (do not crush or chew). Avoid alcohol. You may experience headache, vomiting, or diarrhea. Report persistent abdominal discomfort; chest pain; persistent headache; unresolved diarrhea; excessive fatigue; increased muscle, joint, or body pain; or changes in urinary pattern.
Geriatric Considerations
Dosage adjustment not required.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
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 (n=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).
Acute ulcer: Postendoscopy therapy: Intravenous omeprazole has 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 (Lin, 1998; Lau, 2000). 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.
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
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety or dizziness; may rarely produce confusion, depression, dysarthria, hallucinations, nervousness, or somnolence
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess other medications for effectiveness and interactions (cytochrome P450 enzyme substrate), especially those drugs in which absorption is determined by an acidic gastric pH.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Granules for suspension, delayed release, enteric coated, oral:
Protonix®: 40 mg/packet (30s)
Injection, powder for reconstitution:
Protonix®: 40 mg [contains edetate disodium]
Tablet, delayed release, oral: 20 mg, 40 mg
Protonix®: 20 mg, 40 mg
Pricing: U.S. (www.drugstore.com)
Tablet, EC (Pantoprazole Sodium)
20 mg (30): $109.99
Tablet, EC (Protonix)
20 mg (30): $170.99
40 mg (30): $169.98
Extemporaneously Prepared
A 2 mg/mL pantoprazole oral suspension may be made with pantoprazole tablets, sterile water, and sodium bicarbonate powder. Remove the Protonix® imprint from twenty 40 mg tablets with a paper towel dampened with ethanol (improves the look of product). Let tablets air dry. Crush the tablets in a mortar and reduce to a fine powder. Transfer to a 600 mL beaker, and add 340 mL sterile water. Place beaker on a magnetic stirrer. Add 16.8 g of sodium bicarbonate powder and stir for about 20 minutes until the tablet remnants have disintegrated. While stirring, add another 16.8 g of sodium bicarbonate powder and stir for about 5 minutes until powder has dissolved. Add enough sterile water for irrigation to bring the final volume to 400 mL. Mix well. Transfer to amber-colored bottle. Label "shake well" and "refrigerate". Stable for 62 days refrigerated.
Dentinger PJ, Swenson CF, and Anaizi NH, “Stability of Pantoprazole in an Extemporaneously Compounded Oral Liquid,” Am J Health Syst Pharm, 2002, 59(10):953-6.
References
Bardhan KD, Dillon J, Axon AT, et al, “Triple Therapy for Helicobacter pylori Eradication: A Comparison of Pantoprazole Once Versus Twice Daily,” Aliment Pharmacol Ther, 2000, 14(1):59-67.
Brunner G, Luna P, Hartmann M, et al, “Optimizing the Intragastric pH as a Supportive Therapy in Upper GI Bleeding,” Yale J Biol Med, 1996, 69(3):225-31.
Chey WD, Wong BC, et al, “American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection,” Am J Gastroent, 2007, 102(8):1808-25.
Cockayne SE, Glet RJ, Gawkrodger DJ, et al, “Severe Erythrodermic Reactions to the Proton Pump Inhibitors Omeprazole and Lansoprazole,” Br J Dermatol,1999, 141(1):173-5.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” [published correction appears in Crit Care Med, 2008, 36(4):1394-6], Crit Care Med, 2008, 36(1):296-327.
Escourrou J, Deprez P, Saggioro A, et al, “Maintenance Therapy With Pantoprazole 20 mg Prevents Relapse of Reflux Oesophagitis,” Aliment Pharmacol Ther, 1999, 13(11):1481-91.
Johnson CE, “Stability of Pantoprazole in 0.9% Sodium Chloride Injection in Polypropylene Syringes,” Am J Health Syst Pharm, 2005, 62(22):2410-2.
Jung R and MacLaren R, “Proton-Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients,” Ann Pharmacother, 2002, 36(12):1929-37.
Kahrilas PJ, Shaheen NJ, Vaezi MF, et al, “American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease,” Gastroenterology, 2008, 135(4):1383-91.
Lau JY, Leung WK, Wu JC, et al, “Omeprazole Before Endoscopy in Patients With Gastrointestinal Bleeding,” N Engl J Med, 2007, 356(16):1631-40.
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.
Lew EA, Pisegna JR, Starr JA, et al, “Intravenous Pantoprazole Rapidly Controls Gastric Acid Hypersecretion in Patients With Zollinger-Ellison Syndrome,” Gastroenterology, 2000, 118(4):696-704.
Lin HJ, Lo WC, Lee FY, et al, “A Prospective Randomized Comparative Trial Showing That Omeprazole Prevents Rebleeding in Patients With Bleeding Peptic Ulcer After Successful Endoscopic Therapy,” Arch Intern Med, 1998, 158(1):54-8.
Madrazo-de la Garza A, Dibildox M, Vargas A, et al, “Efficacy and Safety of Oral Pantoprazole 20 mg Given Once Daily for Reflux Esophagitis in Children,” J Pediatr Gastroenterol Nutr, 2003, 36(2):261-5.
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Last full review/revision May 2011
Content last modified May 2011
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