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Pantoprazole

Pronunciation

Pronunciation

(pan TOE pra zole)

Index Terms

  • Pantoprazole Magnesium
  • Pantoprazole Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral:

Protonix: 40 mg (1 ea, 30 ea) [contains polysorbate 80]

Solution Reconstituted, Intravenous:

Protonix: 40 mg (1 ea) [contains edetate disodium]

Generic: 40 mg (1 ea)

Tablet Delayed Release, Oral:

Protonix: 20 mg, 40 mg

Generic: 20 mg, 40 mg

Brand Names: U.S.

  • Protonix

Pharmacologic Category

  • Proton Pump Inhibitor
  • Substituted Benzimidazole

Pharmacology

Proton pump inhibitor, suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump

Absorption

Rapid, well absorbed

Distribution

Vd:

Children and Adolescents (Kearns 2008): IV: 2 to 16 years: 0.22 ± 0.14 L/kg; Oral: 5 to 16 years: 0.24 ± 0.09 L/kg

Adults: 11 to 24 L

Metabolism

Extensively hepatic; CYP2C19 (demethylation), CYP3A4; no evidence that metabolites have pharmacologic activity

Excretion

Urine (71% as metabolites); feces (18%); pantoprazole clearance increased with weight and age (Peterson, 2009)

Onset of Action

Onset of action: Acid secretion: Oral: 2.5 hours; IV: 15 to 30 minutes

Maximum effect: IV: 2 hours

Time to Peak

Children and Adolescents (Kearns 2008): IV: 2 to 16 years: 0.34 ± 0.12 hours; Oral: 5 to 16 years: 2.54 ± 0.72 hours

Adults: Oral: 2.5 hours

Duration of Action

Oral, IV: 24 hours

Half-Life Elimination

Neonates (PMA: 37 to 44 weeks): ~3 hours (Ward 2010)

Children and Adolescents (Kearns 2008): IV: 2 to 16 years: 1.22 ± 0.68 hours; Oral: 5 to 16 years: 1.27 ± 1.29 hours

Adults: 1 hour; increased to 3.5 to 10 hours with CYP2C19 deficiency

Protein Binding

98%, primarily to albumin

Special Populations: Hepatic Function Impairment

Increase in serum elimination half-life to 7 to 9 hours; AUC increases by 5- to 7-fold.

Special Populations: Elderly

Moderate increase in AUC (43%) and Cmax (26%) after oral administration.

Special Populations: Gender

A modest increase in AUC and Cmax in women.

Use: Labeled Indications

Oral:

Erosive esophagitis associated with gastroesophageal reflux disease: Short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis in adults and pediatric patients 5 years and older.

Maintenance of healing of erosive esophagitis: Maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gastroesophageal reflux disease (GERD).

Pathological hypersecretory conditions, including Zollinger-Ellison syndrome: Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

IV:

Gastroesophageal reflux disease associated with a history of erosive esophagitis: Short-term treatment (7 to 10 days) of adult patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis.

Pathological hypersecretion associated with Zollinger-Ellison syndrome: Treatment of adult patients with pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Canadian labeling: Additional use (not in US labeling): Oral: Peptic ulcer disease (eg, duodenal or gastric ulcer); adjunct treatment with antibiotics for Helicobacter pylori eradication; NSAID-induced ulcer prophylaxis (Pantoloc)

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 (parenteral formulation)

Contraindications

Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, urticaria) to pantoprazole, other substituted benzimidazole proton pump inhibitors, or any component of the formulation

Dosing: Adult

Erosive esophagitis associated with GERD:

Oral:

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. Note: Canadian labeling recommends initial treatment for up to 4 weeks and an additional 4 weeks in patients who have not healed after the initial 4-week course. Lower doses (20 mg once daily) have been used successfully in mild GERD treatment (Dettmer, 1998).

Maintenance of healing: 40 mg once daily (US labeling) or 20 to 40 mg once daily (Canadian labeling); 20 mg once daily has been used successfully in maintenance of healing (Escourrou, 1999). Note: Has not been studied beyond 12 months.

IV: 40 mg once daily for 7 to 10 days

Pathological hypersecretory conditions, including Zollinger-Ellison syndrome:

Oral: Initial: 40 mg twice daily; adjust dose based on patient needs; doses up to 240 mg daily have been administered

IV: 80 mg every 12 hours; adjust dose based on acid output measurements; 160 to 240 mg daily in divided doses has been used for a limited period (up to 7 days)

Prevention of rebleeding in peptic ulcer bleed (off-label use): IV:

Continuous infusion: Loading dose of 80 mg, followed by 8 mg/hour infusion for 72 hours (Barkun, 2010; Zargar, 2006).

Intermittent dosing: Loading dose of 80 mg followed by either 40 mg every 12 hours for 72 hours (Hung, 2007; Yamada, 2012) or 40 mg every 6 hours for 72 hours (Hsu, 2009). May also administer 40 mg every 12 hours for 72 hours without a loading dose (Yuksel, 2008).

Note: After completion, continue therapy with a single daily-dose oral PPI for a duration dictated by the underlying etiology (Barkun, 2010).

Helicobacter pylori eradication (off-label use in US): Oral:

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 to 14 days

Penicillin allergy: 40 mg twice daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10 to 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 daily for 10 to 14 days

Canadian labeling: 40 mg twice daily administered with clarithromycin 500 mg twice daily and either metronidazole 500 mg or amoxicillin 1,000 mg twice daily for 7 days

Peptic ulcer disease (Canadian labeling): Oral: Treatment: 40 mg once daily for 2 weeks (duodenal ulcer) or 4 weeks (gastric ulcer); may extend therapy for an additional 2 or 4 weeks (based on indication) for inadequate healing

NSAID-induced ulcer prophylaxis (Canadian labeling): Oral: 20 mg once daily

Symptomatic GERD (Canadian labeling): Oral: Treatment: 40 mg once daily for up to 4 weeks; failure to achieve adequate symptom relief after the initial 4 weeks of therapy warrants further evaluation

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Erosive esophagitis associated with GERD:

Oral:

Children <5 years: Dosage not established.

Children ≥5 years: Note: Consider a dose reduction in known CYP2C19 poor metabolizers.

≥15 to <40 kg: 20 mg once daily for up to 8 weeks

≥40 kg: 40 mg once daily for up to 8 weeks

IV: Dosage not established

Dosing: Renal Impairment

US labeling: No dosage adjustment necessary; pantoprazole is not removed by hemodialysis.

Canadian labeling: Use is not recommended in combination therapy of Helicobacter pylori in patients with severe renal impairment (has not been studied).

Dosing: Hepatic Impairment

US labeling: No dosage adjustment necessary; doses >40 mg daily have not been evaluated.

Canadian labeling:

Mild-moderate impairment: No dosage adjustment necessary.

Severe impairment: IV, Oral: Manufacturer labeling suggests a maximum dose of 20 mg daily. Use in combination therapy of Helicobacter pylori is not recommended in patients with severe hepatic impairment (has not been studied).

Reconstitution

15-minute infusion: Reconstitute vial(s) with 10 mL of NS and then dilute with 100 mL or 80 mL of D5W, NS, or LR to a final concentration of ~0.4 mg/mL for a 40 mg dose and ~0.8 mg/mL for an 80 mg dose, respectively.

2-minute infusion: Reconstitute with 10 mL of NS to a final concentration of ~4 mg/mL.

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):953-6.12040734

Administration

IV: Flush IV line before and after administration. In-line filter not required.

2-minute infusion: The volume of reconstituted solution (4 mg/mL) 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).

Continuous infusion: May also be administered as a continuous infusion for the prevention of rebleeding with in peptic ulcer bleed (off-label use).

Oral:

Tablet: Should be swallowed whole, do not crush or chew. May administer with or without food; concomitant administration of antacids does not affect absorption.

Delayed-release oral suspension: Should only be administered in apple juice or applesauce and taken ~30 minutes before a meal; do not chew or crush granules. 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.

Dietary Considerations

IV: Due to EDTA in preparation, zinc supplementation may be needed in patients prone to zinc deficiency.

Compatibility

Stable in D5W, LR, NS.

Y-site administration: Incompatible with acyclovir, amikacin, amiodarone, amphotericin B, atropine, caffeine citrate, cefoxitin, cefotaxime, ceftazidime, 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.

Compatibility in syringe: Incompatible with 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.

Storage

Oral: Store tablet and oral suspension at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

IV: Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Protect from light prior to reconstitution; upon reconstitution, protection from light is not required. Per manufacturer’s labeling, reconstituted solution is stable at room temperature for up to 6 hours; further diluted (admixed) solution in D5W, LR, or NS should be stored at room temperature and used within 24 hours from the time of initial reconstitution. However, studies have shown that reconstituted solution (4 mg/mL) in polypropylene syringes is stable up to 96 hours at room temperature (Johnson 2005). Upon further dilution, the admixed solution should be used within 96 hours from the time of initial reconstitution. 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.

Drug Interactions

Amphetamine: Proton Pump Inhibitors may increase the absorption of Amphetamine. Monitor therapy

Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: See full drug interaction monograph for details. Consider therapy modification

Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as antacids or H2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Consider therapy modification

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. 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. 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. Consider therapy modification

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dabigatran Etexilate: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates. Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: Proton Pump Inhibitors may decrease the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Proton Pump Inhibitors. Management: Seek alternatives to the proton pump inhibitor when possible. If concomitant therapy cannot be avoided, monitor for diminished effects of both drugs. Consider therapy modification

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Avoid combination

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. 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. Monitor therapy

Dextroamphetamine: Proton Pump Inhibitors may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates. Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Avoid combination

Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Monitor therapy

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Consider therapy modification

Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Monitor therapy

Iron Salts: Proton Pump Inhibitors may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Monitor therapy

Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. 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. Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: Avoid the use of PPIs at doses greater than the equivalent of omeprazole 20 mg, avoid administration of PPIs within 2 hours prior to ledipasvir dosing, and avoid use of PPIs in combination with food. Consider therapy modification

Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. Monitor therapy

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. Consider therapy modification

Methotrexate: Proton Pump Inhibitors may increase the serum concentration of Methotrexate. 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. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Proton Pump Inhibitors may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be decreased. Monitor therapy

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. 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. Avoid combination

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Consider therapy modification

PAZOPanib: Proton Pump Inhibitors may decrease the serum concentration of PAZOPanib. Avoid combination

Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Consider therapy modification

Raltegravir: Proton Pump Inhibitors may increase the serum concentration of Raltegravir. Monitor therapy

Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Avoid combination

Riociguat: Proton Pump Inhibitors may decrease the serum concentration of Riociguat. Monitor therapy

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Avoid combination

Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Monitor therapy

Velpatasvir: Proton Pump Inhibitors may decrease the serum concentration of Velpatasvir. Avoid combination

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Management: In patients receiving omeprazole 40 mg/day or greater, reduce omeprazole dose by half when initiating voriconazole. Monitor therapy

Test Interactions

False-positive urine screening tests for tetrahydrocannabinol (THC) have been noted in patients receiving proton pump inhibitors, including pantoprazole.

Adverse Reactions

>10%: Central nervous system: Headache (adults 12%; children >4%)

1% to 10%:

Cardiovascular: Facial edema (≤4%), edema (≤2%)

Central nervous system: Dizziness (≤4%), vertigo (≤4%), depression (≤2%)

Dermatologic: Skin rash (adults ≤2%; children >4%), urticaria (≤4%), pruritus (≤2%), skin photosensitivity (≤2%)

Endocrine & metabolic: Increased serum triglycerides (≤4%)

Gastrointestinal: Diarrhea (≤9%), abdominal pain (children >4%), vomiting (≥4%), constipation (≤4%), flatulence (children ≤4%), nausea (children ≤4%), xerostomia (≤2%)

Hematologic & oncologic: Leukopenia (≤2%), thrombocytopenia (≤2%)

Hepatic: Abnormal hepatic function tests (≤4%), hepatitis (≤2%)

Hypersensitivity: Hypersensitivity reaction (≤4%)

Local: Inflammation at injection site (≤2%)

Neuromuscular & skeletal: Arthralgia (≤4%), myalgia (≤4%), increased creatine phosphokinase (≤4%)

Ophthalmic: Blurred vision (≤2%)

Respiratory: Upper respiratory tract infection (children >4%)

Miscellaneous: Fever (adults ≤2%; children >4%)

<1% (Limited to important or life-threatening): Ageusia, agranulocytosis, albuminuria, anaphylaxis (including anaphylactic shock), anemia, angioedema, angina pectoris, aphthous stomatitis, atrial fibrillation, atrial flutter, atrophic gastritis, biliary colic, bone fracture, bursitis, candidiasis (gastrointestinal), cardiac arrhythmia, cardiac failure, cataract, cholecystitis, cholelithiasis, chronic renal disease (Lazarus 2016), Clostridium difficile-associate diarrhea , colitis, contact dermatitis, cystitis, deafness, dehydration, diabetes mellitus, diplopia, duodenitis, dysmenorrhea, dysphagia, dysuria, ecchymoses, ECG abnormality, eosinophilia, epididymitis, epistaxis, erythema multiforme, exacerbation of asthma, extraocular palsy, fungal dermatitis, gastric ulcer, gastrointestinal carcinoma, gastrointestinal hemorrhage, gingivitis, glaucoma, glossitis, glycosuria, goiter, gout, hallucination, hematemesis, hematuria, hemorrhage, hepatic failure, hepatotoxicity (idiosyncratic) (Chalasani 2014), hernia, hyperbilirubinemia, hyperesthesia, hypertension, hyperkinesia, hyperuricemia, hypokinesia, hypomagnesemia, hyponatremia, hypotension, impotence, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, increased serum creatinine, interstitial nephritis, ischemic heart disease, jaundice, leukocytosis, lichenoid dermatitis, maculopapular rash, mastalgia, melena, myocardial infarction, neoplasm, nephrolithiasis, neuralgia, neuritis, optic neuropathy (including anterior ischemic), oral mucosa ulcer, ostealgia, palpitations, pancreatitis, pancytopenia, paresthesia, periodontitis, pneumonia, pyelonephritis, rectal hemorrhage, renal pain, retinal vascular disease, rhabdomyolysis, scrotal edema, seizure, Stevens-Johnson syndrome, stomatitis, syncope, tachycardia, tenosynovitis, thrombosis, tinnitus, tongue discoloration, toxic epidermal necrolysis, urethritis, visual disturbance

Warnings/Precautions

Concerns related to adverse effects:

• Carcinoma: Benign and malignant neoplasia has been observed in long-term (2-year) rodent studies; while not reported in humans, the relevance of these findings in regards to tumorigenicity in humans is not known.

Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to elderly patients. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of pantoprazole.

• 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 (≥1 year) 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 2 weeks of stopping.

• Infusion-related reactions: Thrombophlebitis and serious hypersensitivity reactions, including anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with IV administration.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam, 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of PPIs 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. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel. Of the PPIs, pantoprazole has the lowest degree of CYP2C19 inhibition in vitro (Li, 2004) and has been shown to have less effect on conversion of clopidogrel to its active metabolite compared to omeprazole (Angiolillo, 2011). In contrast to these warnings, 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).

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.

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 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2007). Safety and efficacy of IV treatment for GERD and a history of erosive esophagitis beyond 10 days have not been established; transition from IV to oral therapy as soon possible.

Monitoring Parameters

Hypersecretory disorders: Acid output measurements, target level <10 mEq/hour (<5 mEq/hour if prior gastric acid-reducing surgery)

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Most available studies have not shown an increased risk of major birth defects following maternal use of proton pump inhibitors during pregnancy (Diav-Citrin, 2005; Erichsen, 2012; Matok, 2012; Pasternak, 2010). When treating GERD in pregnancy, PPIs may be used when clinically indicated (Katz, 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, diarrhea, nausea, vomiting, flatulence, or joint pain. Have patient report immediately to prescriber signs of low magnesium (mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), severe dizziness, passing out, severe abdominal pain, bone pain, chills, pharyngitis, excessive weight loss, injection site irritation, signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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