Proton Pump Inhibitor

Aka: Proton Pump Inhibitor, PPI Therapy, Omeprazole, Prilosec, Lansoprazole, Prevacid, Esomeprazole, Nexium, Pantoprazole, Protonix, Rabeprazole, Aciphex

1. Indications
   1. Peptic Ulcer Disease
   2. Gastroesophageal Reflux
2. Contraindications
   1. Hypersensitivity to Proton Pump Inhibitors
   2. Use with caution in severe liver disease
3. Precautions: Pregnancy and Lactation
   1. Pregnancy Category C: Omeprazole
   2. Pregnancy Category B: Other agents
   3. Avoid PPI agents in Lactation
4. 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
5. 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
6. Dosing (Take 30 minutes prior to a meal)
   1. Omeprazole (Prilosec)
      1. Duodenal Ulcer or erosive esophagitis: 20 mg po qd
      2. Gastric Ulcer: 40 mg po qd
      3. Generic in 2002
   2. Lansoprazole (Prevacid)
      1. Duodenal Ulcer or erosive esophagitis: 15 mg po qd
      2. Gastric Ulcer: 30 mg po qd
   3. Pantoprazole (Protonix)
      1. Duodenal Ulcer or erosive esophagitis: 40 mg PO qd
      2. Parenteral dosing available
   4. Rabeprazole (Aciphex)
      1. Erosive esophagitis: 20 mg PO qd
   5. Esomeprazole (Nexium)
      1. Erosive esophagitis: 20 to 40 mg PO qd
7. Precautions
   1. Longterm Proton Pump Inhibitor use has significant risks (see adverse effects below)
   2. 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
   3. 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)
8. 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
9. 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
10. 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 level decreases specific to Prevacid (CYP 450)
       1. Theophylline
11. 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
12. Adverse Effects
    1. Headache
    2. Diarrhea
    3. Abdominal Pain
    4. Nausea
13. Adverse Effects: Complications of prolonged use
    1. Clostridium difficile
       1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
    2. Hypomagnesemia
    3. Hip Fracture risk increase
       1. Possibly associated with Vitamin D decreased serum levels
    4. Vitamin B12 Deficiency
       1. Bradford (1999) Pharmacother 33:641-3
    5. Gastric Carcinoma
       1. Originally bi-annual Gastrin levels recommended
       2. Routine Gastrin levels not currently necessary
    6. 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
14. References
    1. (2012) Prescr Lett 19(3): 14
    2. (2001) Med Lett Drugs Ther 43(1103):36-7
    3. Vanderhoff (2002) Am Fam Physician 66(2):273-80