II. Contraindications

  1. Hypersensitivity to Proton Pump Inhibitors
  2. Use with caution in severe liver disease

III. Mechanism

  1. Benzimidazole Proton Pump Inhibitors
  2. Binds proton pump of parietal cell
  3. Inhibits >90% of total daily gastric acid production
  4. PPIs irreversibly bind proton pump

IV. Pharmacokinetics

  1. All PPIs have short plasma half life of 1-2 hours
  2. Effect is delayed 5-7 days until proton pumps are fully blocked

V. Dosing (Take 30 minutes prior to a meal)

  1. Omeprazole (Prilosec)
    1. Duodenal Ulcer or erosive esophagitis: 20 mg orally daily
    2. Gastric Ulcer: 40 mg po qd
    3. Generic in 2002, OTC
  2. Lansoprazole (Prevacid)
    1. Duodenal Ulcer or erosive esophagitis: 15 mg orally daily
    2. Gastric Ulcer: 30 mg po qd
    3. Generic, OTC
  3. Pantoprazole (Protonix)
    1. Duodenal Ulcer or erosive esophagitis: 40 mg orally daily
    2. Parenteral dosing available
  4. Rabeprazole (Aciphex)
    1. Erosive esophagitis: 20 mg orally daily
  5. Dexlansoprazole (Dexilant)
    1. Dose: 30 mg daily
  6. Esomeprazole Magnesium (Nexium)
    1. Erosive esophagitis: 20 to 40 mg orally daily
    2. Generic 40 mg tab in May 2014, and 20 mg tab planned for OTC
  7. Esomeprazole Strontium
    1. Dose 49.3 mg orally daily is equivalent to Esomeprazole Magnesium (Nexium) 40 mg
    2. Created as a patent extender in 2014 by changing the Esomeprazole salt from Magnesium to strontium
    3. Do not use in children due to possible bone adverse effects with Strontium
    4. Very expensive ($150/month in 2014) and no advantage over soon to be generic Esomeprazole Magnesium (Nexium)
    5. (2014) Presc Lett 21(2): 8

VI. Precautions

  1. Longterm Proton Pump Inhibitor use has significant risks (see adverse effects below)
  2. Maximize non-pharmacologic measures (e.g. GERD precautions) to reduce the need for longterm Proton Pump Inhibitor
  3. Balance adverse effects against the risks of discontinuing acid suppression
    1. Barrett's Esophagus requires longterm Proton Pump Inhibitor for acid suppression to prevent progression to Esophageal Cancer
    2. Hiatal Hernia will likely require longterm Proton Pump Inhibitors
  4. Use the lowest effective dose and for the shortest duration that controls symptoms
    1. Consider discontinuation protocol below
    2. Consider less complete acid suppression (e.g. H2 Blocker)
    3. Consider limited 8 week course of PPI for Erosive Gastritis and then taper to other acid suppression (e.g. H2 Blocker)
    4. Consider brief intermittent use (e.g. 2-4 weeks) for exacerbations

VII. Precautions: Pregnancy and Lactation

  1. Pregnancy Category C: Omeprazole
  2. Pregnancy Category B: Other agents
  3. Avoid PPI agents in Lactation

VIII. Protocol: Discontinuation

  1. Use H2 Blocker (e.g. Ranitidine) when symptoms arise on days a Proton Pump Inhibitor is not taken
  2. Taper over 4-6 weeks
    1. First, take every other day
    2. Then, take every third day
    3. Then, continue to increase the interval between doses

IX. Efficacy

  1. Gastroesophageal Reflux treatment with Omeprazole
    1. Patients with healed esophagitis (n=175)
    2. Treated with 1 of 3 drugs to prevent recurrence
      1. Ranitidine: 49% Remission
      2. Ranitidine and Cisapride: 66% Remission
      3. Cisapride: 54% Remission
      4. Omeprazole 80% Remission
      5. Omeprazole and Cisapride: 89% Remission
  2. References
    1. Vigneri (1995) N Engl J Med 333:1106-10

X. Drug Interactions

  1. Decreased Absorption (due to increased gastric pH)
    1. Griseofulvin
    2. Ketoconazole
    3. Itraconazole
    4. Iron Salts
    5. Vitamin B12
    6. Cefpodoxime
    7. Enoxacin
  2. Increased Absorption (due to increased gastric pH)
    1. Nifedipine (Procardia)
    2. Digoxin
  3. Drug level increases specific to Prilosec (CYP 450)
    1. Carbamazepine (Tegretol)
    2. Diazepam (Valium)
    3. Phenytoin (Dilantin)
    4. Warfarin (Coumadin)
    5. Methotrexate
  4. Drug lowered efficacy specific to Prilosec
    1. Clopidogrel (Plavix)
      1. Increased major coronary events occurred within one year of PTCA attributed to Omeprazole's interaction with Clopidogrel
        1. Gaglia (2010) Am J Cardiol 105(6): 833-8
      2. Pantoprazole (Protonix) does not lower Clopidogrel efficacy
        1. Juurlink (2009) CMAJ 180(7): 713-8
      3. Avoid Omeprazole following PTCA and coronary stenting (consider H2 Blocker or Pantoprazole instead)
  5. Drug level decreases specific to Prevacid (CYP 450)
    1. Theophylline

XI. Efficacy: Relative Potency

  1. General
    1. Potency and outcomes appear to be similar for all PPI
    2. Literature appears to offer conflicting results
    3. Most potent agents appear to be
      1. Rabeprazole (Aciphex)
      2. Esomeprazole (Nexium)
  2. References
    1. Dammann (1999) Eur J Gastroenterol Hepatol 11:1277-82
    2. Williams (1999) Aliment Pharmacol Ther 13(suppl 3):3
    3. Hartmann (1996) Aliment Pharmacol Ther 10(3):359-66
    4. Bastaki (2000) J Physiol Paris 94(1):19-23
    5. Florent (1997) Eur J Gastroenterol Hepatol 9(2):195
    6. Spencer (2000) Drugs 60:321

XII. Adverse Effects

XIII. Adverse Effects: Complications of prolonged use

  1. Clostridium difficile
    1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
  2. Hypomagnesemia
  3. Decreased Bone Mineral Density
    1. Hip Fracture, wrist Fracture and spine Fracture risk increase (Osteoporosis related Fracture sites)
    2. Possibly associated with Vitamin D decreased serum levels
    3. Targownik (2012) Am J Gastroenterol 107:1361–9
  4. Vitamin B12 Deficiency
    1. Bradford (1999) Pharmacother 33:641-3
  5. Iron Deficiency Anemia
    1. Decreased iron absorption in the absence of adequate gastric acid
  6. Gastric Carcinoma
    1. Originally bi-annual Gastrin levels recommended
    2. Routine Gastrin levels not currently necessary
  7. Community Acquired Pneumonia
    1. Risk increases with PPI dosage
    2. H2-Blockers also conferred risk, but less than PPI
    3. Laheij (2004) JAMA 292:1955-60

Images: Related links to external sites (from Google)

Cost: Medications

Omeprazole (on 2/9/2012 at DrugStore.com)
Omeprazole 20mg Delayed Release Capsule #90 for $99.97 ($1.11/unit)
Omeprazole 14 20mg Enteric Coated Tabs Box #1 for $19.99 ($19.99/unit)
Omeprazole 40mg Delayed Release Capsule #30 for $195.00 ($6.50/unit)
Omeprazole 10mg Delayed Release Capsule #30 for $34.99 ($1.17/unit)
Omeprazole-Sodium Bicarbonate (on 2/9/2012 at DrugStore.com)
Omeprazole-Sodium Bicarbonate Capsules #30 for $185.99 ($6.20/unit)
PriLOSEC (on 2/9/2012 at DrugStore.com)
PriLOSEC 30 10mg Delayed Release Capsule Bottle #1 for $170.99 ($170.99/unit)
PriLOSEC 20mg Delayed Release Capsule #30 for $195.99 ($6.53/unit)
PriLOSEC 40mg Delayed Release Capsule #30 for $291.00 ($9.70/unit)
PriLOSEC OTC (on 2/9/2012 at DrugStore.com)
PriLOSEC OTC 14 20mg Enteric Coated Tabs Box #1 for $21.99 ($21.99/unit)
Lansoprazole (on 2/9/2012 at DrugStore.com)
Lansoprazole 15mg Delayed Release Capsule #30 for $105.99 ($3.53/unit)
Lansoprazole 30mg Delayed Release Capsule #30 for $99.99 ($3.33/unit)
Lansoprazole 15mg Dispersible Tablet #30 for $162.98 ($5.43/unit)
Lansoprazole 30mg Dispersible Tablet #30 for $162.98 ($5.43/unit)
Prevacid (on 2/9/2012 at DrugStore.com)
Prevacid 15mg Delayed Release Capsule #30 for $196.00 ($6.53/unit)
Prevacid SoluTab (on 2/9/2012 at DrugStore.com)
Prevacid SoluTab 100 15mg Dispersible Tablet Box #1 for $631.98 ($631.98/unit)
Prevacid SoluTab 30mg Dispersible Tablet #30 for $198.99 ($6.63/unit)
NexIUM (on 2/9/2012 at DrugStore.com)
NexIUM 30 10mg Packets Box #1 for $195.99 ($195.99/unit)
NexIUM 30 20mg Packets Box #1 for $195.99 ($195.99/unit)
NexIUM 30 40mg Packets Box #1 for $195.99 ($195.99/unit)
NexIUM 20mg Delayed Release Capsule #30 for $200.99 ($6.70/unit)
NexIUM 40mg Delayed Release Capsule #30 for $184.99 ($6.17/unit)
Pantoprazole Sodium (on 2/9/2012 at DrugStore.com)
Pantoprazole Sodium 20mg Enteric Coated Tabs #30 for $15.99 ($0.53/unit)
Pantoprazole Sodium 40mg Enteric Coated Tabs #30 for $15.99 ($0.53/unit)
Protonix (on 2/9/2012 at DrugStore.com)
Protonix 40mg Enteric Coated Tabs #30 for $190.00 ($6.33/unit)
Protonix 20mg Tablets #30 for $186.38 ($6.21/unit)
Protonix 30 40mg Packets Box #1 for $175.98 ($175.98/unit)
Aciphex (on 2/9/2012 at DrugStore.com)
Aciphex 20mg Enteric Coated Tabs #30 for $249.99 ($8.33/unit)
Dexilant (on 2/9/2012 at DrugStore.com)
Dexilant 30mg Delayed Release Capsule #30 for $153.45 ($5.12/unit)
Dexilant 60mg Delayed Release Capsule #30 for $149.99 ($5.00/unit)

Ontology: Omeprazole (C0028978)

Definition (NCI) A benzimidazole with selective and irreversible proton pump inhibition activity. Omeprazole forms a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+ - K+) ATPase found on the secretory surface of parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion. This agent exhibits no anticholinergic activities and does not antagonize histamine H2 receptors.
Definition (MSH) A highly effective inhibitor of gastric acid secretion used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-EXCHANGING ATPASE) in the proton pump of GASTRIC PARIETAL CELLS.
Definition (CSP) substituted benzimidazole used as a gastric acid secretion inhibitor.
Definition (NCI) A drug that inhibits gastric acid secretion.
Definition (PDQ) A benzimidazole with selective and irreversible proton pump inhibition activity. Omeprazole forms a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+ - K+) ATPase found on the secretory surface of parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion. This agent exhibits no anticholinergic properties and does not antagonize histamine H2 receptors. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42309&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42309&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C716" NCI Thesaurus)
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH D009853
SnomedCT 25673006, 387137007
English Omeprazole, 1H-Benzimidazole, 5-methoxy-2-(((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)sulfinyl)-, OMEP, 5-Methoxy-2-(((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole, omeprazole, omeprazole (medication), OMEPRAZOLE, Omeprazole [Chemical/Ingredient], omeprazole product, Omeprazole (product), Omeprazole (substance)
Swedish Omeprazol
Czech omeprazol
Finnish Omepratsoli
Russian EZOMEPRAZOL, OMEPRAZOL, ОМЕПРАЗОЛ, ЭЗОМЕПРАЗОЛ
Croatian OMEPRAZOL
Polish Omeprazol
Japanese オメプラゾール, オメプラール
Spanish omeprazol (producto), omeprazol (sustancia), omeprazol, Omeprazol
French Oméprazole
German Omeprazol
Italian Omeprazolo
Portuguese Omeprazol

Ontology: lansoprazole (C0050940)

Definition (CHV) a drug used to treat heartburn
Definition (NCI) A substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. Lansoprazole prodrug is converted to an active sulfonamide derivative in the acidic environment of the gastric parietal cell; the sulfonamide derivative binds to the gastric proton pump H+/K+ ATPase and forms a stable disulfide bond with the sulfhydryl group near the potassium-binding site on the luminal side, resulting in inactivation of the ATPase and a reduction in gastric acid secretion. This agent does not have anticholinergic or histamine H2 -receptor antagonistic properties.
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C058687
SnomedCT 108666007, 386888004
English 2-(((3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl)methyl)sulfinyl)-1H-benzimidazole, lansoprazole, lanzoprazole, lansoprazole (medication), LANSOPRAZOLE, lansoprazole [Chemical/Ingredient], lansoprazole (Prevacid), lansor, lansoprazol, Lansoprazole, Lansoprazole (product), Lansoprazole (substance)
Spanish lansoprazol (producto), lansoprazol (sustancia), lansoprazol

Ontology: pantoprazole (C0081876)

Definition (NCI) A substituted benzimidazole and proton pump inhibitor with antacid activity. Pantoprazole is a lipophilic weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulphenamide, which forms an irreversible covalent bond with two sites of the H+/K+-ATPase enzyme located on the gastric parietal cell, thereby inhibiting both basal and stimulated gastric acid production.
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C064276
SnomedCT 317317009, 395821003
English 1H-Benzimidazole, 5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-, pantoprazole, pantoprazole (medication), pantoprazole [Chemical/Ingredient], Pantoprazole, Pantoprazole (product), Pantoprazole (substance), PANTOPRAZOLE
Spanish pantoprazol (producto), pantoprazol (sustancia), pantoprazol

Ontology: Prevacid (C0286036)

Definition (CHV) brand name of lansoprazole a drug used to treat heartburn
Definition (CHV) brand name of lansoprazole a drug used to treat heartburn
Definition (CHV) brand name of lansoprazole a drug used to treat heartburn
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C058687
English prevacid, ogastro, prevacid [brand name], Ogastro, TAP Brand of Lansoprazole, Abbot Brand of Lansoprazole, Prevacid

Ontology: rabeprazole (C0378482)

Definition (NCI) An alpha-pyridylmethylsulfinyl benzimidazole and a selective and irreversible proton pump inhibitor with antisecretory property. Rabeprazole enters the parietal cell and accumulates in the acidic secretory canaliculi where the agent is activated by a proton-catalyzed process that results in the formation of a thiophilic sulfonamide or sulfenic acid. The activated rabeprazole forms covalent bonds with the sulfhydryl amino acids cysteine on the extracellular domain of the proton pump (H+/K+ ATPase) at the secretory surface, thereby inhibiting the transport of hydrogen ions, via exchange with potassium ions, into the gastric lumen. Binding to cysteine 813, in particular, is essential for inhibition of gastric acid production.
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C063129
SnomedCT 421279008, 422225001
English 2-((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methylsulfinyl)-1H-benzimidazole, rabeprazole, Rabeprazole, Rabeprazole (product), Rabeprazole (substance), 2-(((4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole, rabeprazole [Chemical/Ingredient], RABEprazole, RABEPRAZOLE
Spanish rabeprazol (producto), rabeprazol, rabeprazol (sustancia)

Ontology: Prilosec (C0700777)

Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH D009853
German Prilosec
English prilosec, PriLOSEC, Prilosec

Ontology: Aciphex (C0875952)

Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C063129
English Aciphex, aciphex

Ontology: Protonix (C0876139)

Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH C064276
English Protonix, pantoprazole (Protonix), protonixs, protonix

Ontology: Esomeprazole (C0937846)

Definition (NCI) A drug that blocks acid from being made in the stomach. It is used to treat acid reflux disease and to prevent certain types of gastrointestinal ulcers. Esomeprazole is being studied in the prevention of esophageal cancer and in the treatment of other conditions, including side effects of chemotherapy. It is a type of anti-ulcer agent.
Definition (NCI) The S-isomer of omeprazole, with gastric proton pump inhibitor activity. In the acidic compartment of parietal cells, esomeprazole is protonated and converted into the active achiral sulfenamide; the active sulfenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
Definition (MSH) The S-isomer of omeprazole
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH D009853
SnomedCT 317331009, 396047003
Portuguese Esomeprazol
Spanish Esomeprazol, esomeprazol (producto), esomeprazol (sustancia), esomeprazol
German Esomeprazol
English esomeprazole (medication), Esomeprazole [Chemical/Ingredient], esomeprazole, Esomeprazole (product), Esomeprazole (substance), Esomeprazole, ESOMEPRAZOLE

Ontology: Nexium (C0939400)

Definition (CHV) brand name of a drug used to treat heartburn and acid reflux
Definition (CHV) brand name of a drug used to treat heartburn and acid reflux
Definition (MSH) Esomeprazole trade name.
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH D009853
German Nexium
English nexium [brand name], nexium, NexIUM, Nexium