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 [PubMed] (or open in [QxMD Read])

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 [PubMed] (or open in [QxMD Read])
      2. Pantoprazole (Protonix) does not lower Clopidogrel efficacy
        1. Juurlink (2009) CMAJ 180(7): 713-8 [PubMed] (or open in [QxMD Read])
      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 [PubMed] (or open in [QxMD Read])
    2. Williams (1999) Aliment Pharmacol Ther 13(suppl 3):3 [PubMed] (or open in [QxMD Read])
    3. Hartmann (1996) Aliment Pharmacol Ther 10(3):359-66 [PubMed] (or open in [QxMD Read])
    4. Bastaki (2000) J Physiol Paris 94(1):19-23 [PubMed] (or open in [QxMD Read])
    5. Florent (1997) Eur J Gastroenterol Hepatol 9(2):195 [PubMed] (or open in [QxMD Read])
    6. Spencer (2000) Drugs 60:321 [PubMed] (or open in [QxMD Read])

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 [PubMed] (or open in [QxMD Read])
  4. Vitamin B12 Deficiency
    1. Bradford (1999) Pharmacother 33:641-3 [PubMed] (or open in [QxMD Read])
  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 [PubMed] (or open in [QxMD Read])

Images: Related links to external sites (from Google)

Cost: Medications

omeprazole (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
OMEPRAZOLE DR 10 MG CAPSULE Generic $0.24 each
OMEPRAZOLE DR 20 MG CAPSULE Generic $0.06 each
OMEPRAZOLE DR 20 MG TABLET Generic OTC $0.49 each
OMEPRAZOLE DR 40 MG CAPSULE Generic $0.16 each
OMEPRAZOLE-BICARB 20-1,100 CAP Generic $11.03 each
OMEPRAZOLE-BICARB 40-1,100 CAP Generic $10.91 each
prilosec (on 1/1/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
PRILOSEC DR 10 MG SUSPENSION $6.43 each
PRILOSEC DR 20 MG CAPSULE Generic $0.06 each
PRILOSEC DR 40 MG CAPSULE Generic $0.16 each
PRILOSEC OTC 20.6 MG TABLET OTC $0.63 each
lansoprazole (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
LANSOPRAZOLE DR 15 MG CAPSULE Generic $0.88 each
LANSOPRAZOLE DR 30 MG CAPSULE Generic $0.49 each
prevacid (on 7/23/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
PREVACID 15 MG SOLUTAB $9.89 each
PREVACID 24HR DR 15 MG CAPSULE Generic OTC $0.49 each
PREVACID 30 MG SOLUTAB $9.83 each
PREVACID DR 15 MG CAPSULE Generic $0.88 each
PREVACID DR 30 MG CAPSULE Generic $0.49 each
esomeprazole (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
ESOMEPRAZOLE DR 49.3 MG CAP Generic $1.92 each
nexium (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
NEXIUM 24HR 22.3 MG CAPSULE OTC $0.59 each
NEXIUM DR 20 MG PACKET $7.60 each
NEXIUM DR 5 MG PACKET $7.62 each
pantoprazole (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
PANTOPRAZOLE SOD DR 20 MG TAB Generic $0.13 each
PANTOPRAZOLE SOD DR 40 MG TAB Generic $0.12 each
protonix (on 1/1/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
PROTONIX 40 MG SUSPENSION $8.09 each
PROTONIX DR 20 MG TABLET Generic $0.13 each
PROTONIX DR 40 MG TABLET Generic $0.12 each
rabeprazole (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
RABEPRAZOLE SOD DR 20 MG TAB Generic $0.73 each
aciphex (on 1/29/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
ACIPHEX DR 20 MG TABLET Generic $0.73 each
dexilant (on 12/9/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
DEXILANT DR 30 MG CAPSULE $6.50 each
DEXILANT DR 60 MG CAPSULE $6.52 each

Ontology: Omeprazole (C0028978)

Definition (MSH) A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.
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 (NCI_NCI-GLOSS) A drug that inhibits gastric acid secretion.
Definition (CSP) substituted benzimidazole used as a gastric acid secretion inhibitor.
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 Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D009853
SnomedCT 25673006, 387137007
LNC LP18586-5, MTHU004701
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 OMEPRAZOL, ОМЕПРАЗОЛ
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 (MSH) A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.
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 Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064747
SnomedCT 108666007, 386888004
LNC LP171614-3
English lansoprazole (medication), LANSOPRAZOLE, lansoprazole (Prevacid), 2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl)methyl)sulfinyl)benzimidazole, Lansoprazoles, Lansoprazole, Lansoprazol, lansoprazole, Lansoprazole [Chemical/Ingredient], Lansoprazole (product), Lansoprazole (substance)
Czech lanzoprazol
French Lansoprazole
German 2-Benzimidazolyl(3-methyl-4-(2,2,2-trifluorethoxy)-2-pyridyl)methylsulfoxid, Lansoprazol
Italian Lansoprazolo
Russian AGOPTON, АГОПТОН, ЛАНСОПРАЗОЛ, LANSOPRAZOL
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 Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C064276
SnomedCT 317317009, 395821003
LNC LP171628-3
English 1H-Benzimidazole, 5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-, pantoprazole, pantoprazole (medication), pantoprazole [Chemical/Ingredient], PANTOPRAZOLE, Pantoprazole, Pantoprazole (product), Pantoprazole (substance)
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 Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064747
English prevacid, ogastro, prevacid [brand name], Abbot Brand of Lansoprazole, Lansoprazole Abbot Brand, Ogastro, TAP Brand of Lansoprazole, Lansoprazole TAP Brand, Prevacid

Ontology: rabeprazole (C0378482)

Definition (MSH) A 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.
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 Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064750
SnomedCT 421279008, 422225001
LNC LP171632-5
English Rabeprazole (product), Rabeprazole (substance), 2-(((4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole, RABEprazole, 2-((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methylsulfinyl)-1H-benzimidazole, Rabeprazole, rabeprazole, Rabeprazole [Chemical/Ingredient], RABEPRAZOLE
Spanish rabeprazol (producto), rabeprazol, rabeprazol (sustancia)
Czech Rabeprazol
French Rabéprazole
German Rabeprazol, 2-((4-(3-Methoxypropoxy)-3-methyl-2- pyridyl)methylsulfinyl)benzimidazol, Rabeprazolum
Italian Rabeprazolo
Russian PARIET, ПАРИЕТ, DEKSRABEPRAZOL, LY-307640, АЦИФЕКС, ATSIFEKS, РАБЕПРАЗОЛ, E 3810, RABEPRAZOL, ДЕКСРАБЕПРАЗОЛ

Ontology: Prilosec (C0700777)

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

Ontology: Aciphex (C0875952)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064750
English aciphex, AcipHex, Aciphex

Ontology: Protonix (C0876139)

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

Ontology: Esomeprazole (C0937846)

Definition (MSH) The S-isomer of omeprazole.
Definition (MSHCZE) S-izomer omeprazolu, neracemická forma inhibitoru protonové pumpy.
Definition (NCI_NCI-GLOSS) 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.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064098
SnomedCT 317331009, 396047003
LNC LP171396-7
English esomeprazole (medication), esomeprazole, Esomeprazole, Esomeprazole [Chemical/Ingredient], ESOMEPRAZOLE, Esomeprazole (product), Esomeprazole (substance)
Czech esomeprazol
French Ésoméprazole
German Esomeprazol
Italian Esomeprazolo
Russian ЭЗОМЕПРАЗОЛ, EZOMEPRAZOL
Spanish Not Translated[Esomeprazole], esomeprazol (producto), esomeprazol (sustancia), esomeprazol
Portuguese Not Translated[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 magnesium trade name.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D064098
English nexium [brand name], nexium, NexIUM, Nexium, AstraZeneca Brand of Esomeprazole Magnesium
German Nexium
Spanish Nexium
Portuguese Nexium