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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
(pan TOE pra zole)
Generic Available (U.S.)
Yes: Delayed release tablet
Brand Names: U.S.
Brand Names: Canada
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
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 (PPI) 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.
• 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 pantoprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.
• 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 (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. Of the PPIs, pantoprazole has the lowest degree of CYP2C19 inhibition. Therefore, the manufacturer of clopidogrel prefers pantoprazole if concomitant use of a PPI is necessary. 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).
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% to 10%:
Cardiovascular: Chest pain
Central nervous system: Headache (2% to 9%), insomnia (≤1%), anxiety, dizziness, migraine, pain
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
<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, fatigue, 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, hypomagnesemia, hyponatremia, 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 CYP2C19 (major), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP2C19 (moderate); 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
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
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: 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 (Low risk). 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
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
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
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
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
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
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
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: Compatible: Acetazolamide, alprostadil, aminophylline, ampicillin, anidulafungin, cefazolin, cefoxitin, ceftazidime, dimenhydrinate, dopamine, doripenem, furosemide, ketorolac, penicillin G potassium, potassium chloride, procainamide, telavancin, ticarcillin/clavulanate, vasopressin, zidovudine. Incompatible: Acyclovir, amikacin, amiodarone, amphotericin B, atropine, caffeine citrate, cefotaxime, cefuroxime, chlorpromazine, ciprofloxacin, clindamycin, cloxacillin, cyclosporine, dexamethasone sodium phosphate, diazepam, digoxin, diphenhydramine, enalaprilat, esmolol, estrogens (conjugated), fluconazole, hydralazine, hydrocortisone sodium succinate, hydromorphone, indomethacin, isoproterenol, labetalol, levofloxacin, lidocaine, lorazepam, mannitol, meropenem, metoclopramide, moxifloxacin, multiple vitamins, naloxone, nitroprusside, norepinephrine, oxytocin, pancuronium, phenobarbital, piperacillin/tazobactam, potassium phosphate, prochlorperazine edisylate, propofol, propranolol, ranitidine, thiopental, tobramycin, trimethoprim/sulfamethoxazole, vecuronium, verapamil. Variable (consult detailed reference): Calcium chloride, calcium gluconate, caspofungin, cefazolin, ceftriaxone, dimenhydrinate, dobutamine, dopamine, epinephrine, fentanyl, furosemide, gentamicin, heparin, insulin (regular), magnesium sulfate, meperidine, methylprednisolone sodium succinate, metronidazole, midazolam, morphine, nitroglycerin, norepinephrine, octreotide, phenytoin, sodium bicarbonate, vancomycin.
Compatibility in syringe: Compatible: Acetazolamide, alprostadil, aminophylline, ampicillin, penicillin G sodium, piperacillin, potassium chloride, procainamide, ticarcillin/clavulanate, vancomycin, zidovudine. Incompatible: Acyclovir, amikacin, amiodarone, amphotericin B, atropine, caffeine citrate, calcium chloride, calcium gluconate, cefazolin, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chlorpromazine, ciprofloxacin, clindamycin, cloxacillin, cyclosporine, dexamethasone sodium phosphate, diazepam, digoxin, dimenhydrinate, diphenhydramine, dobutamine, dopamine, enalaprilat, epinephrine, estrogens (conjugated), fentanyl, fluconazole, furosemide, gentamicin, heparin, hydralazine, hydrocortisone sodium succinate, hydromorphone, indomethacin, insulin (regular), isoproterenol, labetalol, lidocaine, lorazepam, magnesium sulfate, meperidine, meropenem, methylprednisolone sodium succinate, metoclopramide, midazolam, morphine, naloxone, nitroglycerin, nitroprusside, norepinephrine, octreotide, oxytocin, pancuronium, phenobarbital, phenytoin, piperacillin/tazobactam, potassium phosphate, prochlorperazine edisylate, propranolol, ranitidine, sodium bicarbonate, thiopental, tobramycin, trimethoprim/sulfamethoxazole, vecuronium, verapamil. Variable (consult detailed reference): Propofol.
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, 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® I.V.: 40 mg [contains edetate disodium]
Tablet, delayed release, oral: 20 mg, 40 mg
Protonix®: 20 mg, 40 mg
Pricing: U.S. (www.drugstore.com)
Pack (Protonix)
40 mg (30): $175.98
Tablet, EC (Protonix)
20 mg (30): $186.38
40 mg (30): $190.00
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
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
Lexi-Comp.com
Last full review/revision March 2012
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