II. Indications
- Peptic Ulcer Disease
- Gastroesophageal Reflux
- Erosive Esophagitis
- Zollinger-Ellison Syndrome
III. Contraindications
- Hypersensitivity to Proton Pump Inhibitors
- Use with caution in severe liver disease
IV. Mechanism
- Benzimidazole Proton Pump Inhibitors bind the parietal cell's proton pump (H+/K+ ATPase)
- Inhibits >90% of total daily gastric acid production
- PPIs irreversibly bind proton pump
V. Pharmacokinetics
- All PPIs have short plasma half life of 1-2 hours
- Effect is delayed 5-7 days until proton pumps are fully blocked
VI. Dosing: Adults (Take 30 minutes prior to a meal)
-
Omeprazole (Prilosec)
- Duodenal Ulcer or erosive Esophagitis: 20 mg orally daily
- Gastric Ulcer: 40 mg po qd
- Generic in 2002, OTC
-
Lansoprazole (Prevacid)
- Duodenal Ulcer or erosive Esophagitis: 15 mg orally daily
- Gastric Ulcer: 30 mg po qd
- Generic, OTC
-
Pantoprazole (Protonix)
- Duodenal Ulcer or erosive Esophagitis: 40 mg orally daily
- Parenteral dosing available
-
Rabeprazole (Aciphex)
- Erosive Esophagitis: 20 mg orally daily
-
Dexlansoprazole (Dexilant)
- Dose: 30 mg daily
-
Esomeprazole
Magnesium (Nexium)
- Erosive Esophagitis: 20 to 40 mg orally daily
- Generic 40 mg tab in May 2014, and 20 mg tab planned for OTC
-
Esomeprazole Strontium
- Dose 49.3 mg orally daily is equivalent to EsomeprazoleMagnesium (Nexium) 40 mg
- Created as a patent extender in 2014 by changing the Esomeprazole salt from Magnesium to strontium
- Do not use in children due to possible bone adverse effects with Strontium
- Very expensive ($150/month in 2014) and no advantage over soon to be generic EsomeprazoleMagnesium (Nexium)
- (2014) Presc Lett 21(2): 8
VII. Dosing: Children
-
Lansoprazole (Prevacid)
- Delivery
- May be compounded into liquid for dosing in infants
- May sprinkle opened capsule onto food or into juice
- Available in a disintegrating tablet
- Weight <10 kg (and age 3-12 months)
- Dose: 7.5 mg twice daily or 15 mg daily
- Dose: 1 mg/kg/day (0.5 to 1.6 mg/kg)
- Weight 10-30 kg
- Dose: 15 mg daily
- Weight >30 kg and adults
- Dose: 30 mg daily
- Delivery
-
Omeprazole (Prilosec)
- Delivery
- May sprinkle opened capsule onto food
- Infants
- Dose: 0.7 mg/kg/day
- Weight 5-10 kg (and age >1 year old)
- Dose: 5 mg daily
- Weight 10-20 kg
- Dose: 10 mg daily
- Weight >20 kg
- Dose: 20 mg daily
- Delivery
- References
VIII. Precautions: General
- Longterm Proton Pump Inhibitor use has significant risks (see adverse effects below)
- Avoid >8 weeks of use in elderly (unless serious Esophageal Reflux, Barrett's Esophagus)
- Maximize non-pharmacologic measures (e.g. GERD precautions)
- Balance adverse effects against the risks of discontinuing acid suppression
- Barrett's Esophagus requires longterm Proton Pump Inhibitor
- Acid suppression to prevent progression to Esophageal Cancer
- Hiatal Hernia will likely require longterm Proton Pump Inhibitors
- Barrett's Esophagus requires longterm Proton Pump Inhibitor
- Use the lowest effective dose and for the shortest duration that controls symptoms
- Consider discontinuation protocol below
- Consider less complete acid suppression (e.g. H2 Blocker)
- Consider limited 4 week course of PPI for Duodenal Ulcer
- Consider limited 8 week course of PPI for Erosive Gastritis or Gastric Ulcer
- Then taper to other acid suppression (e.g. H2 Blocker)
- Consider brief intermittent use (e.g. 2-4 weeks) for exacerbations
IX. Protocol: Discontinuation or Deprescribing
- Indications
- Use H2 Blocker (e.g. Ranitidine) when symptoms arise on days a Proton Pump Inhibitor is not taken
- May consider as needed dosing of Proton Pump Inhibitor if symptoms not relieved with H2 Blocker
- Taper over 4-6 weeks
- If taking twice daily, shift to once daily
- Next, take every other day
- Then, take every third day
- Then, continue to increase the interval between doses
X. Lab: Monitoring for longterm Proton Pump Inhibitor
- Serum Creatinine annually
- Serum Vitamin B12 level every 5 years
- Serum Magnesium if symptoms present
- Complete Blood Count every 2 years
- Alexander (2017) PPI Side Effects, Mayo Clinical Reviews, Rochester, MN
XI. Efficacy
-
Gastroesophageal Reflux treatment with Omeprazole
- Patients with healed Esophagitis (n=175)
- Treated with 1 of 3 drugs to prevent recurrence
- Ranitidine: 49% Remission
- Ranitidine and Cisapride: 66% Remission
- Cisapride: 54% Remission
- Omeprazole 80% Remission
- Omeprazole and Cisapride: 89% Remission
- References
XII. Drug Interactions
- Decreased Absorption (due to increased gastric pH)
- Increased Absorption (due to increased gastric pH)
- Other Interactions
- Increases serum chromogranin A levels (False Positive risk in neuroendocrine tumor evaluation)
- Drug level decreases specific to Lansoprazole (CYP 450)
- Drug level increases specific to Omeprazole (CYP 450)
- Drug lowered efficacy specific to Omeprazole
- Clopidogrel (Plavix)
- Increased major coronary events occurred within one year of PTCA
- Attributed to Omeprazole's interaction with Clopidogrel
- Gaglia (2010) Am J Cardiol 105(6): 833-8 [PubMed]
- Pantoprazole (Protonix) does not lower Clopidogrel efficacy
- Avoid Omeprazole following PTCA and coronary stenting
- Consider H2 Blocker or Pantoprazole instead
- As of 2015, no consistent Drug Interaction between Proton Pump Inhibitors and Clopidogrel
- Increased major coronary events occurred within one year of PTCA
- Clopidogrel (Plavix)
XIII. Efficacy: Relative Potency
-
General
- Potency and outcomes appear to be similar for all PPI
- Literature appears to offer conflicting results
- Most potent agents appear to be
- References
- Dammann (1999) Eur J Gastroenterol Hepatol 11:1277-82 [PubMed]
- Williams (1999) Aliment Pharmacol Ther 13(suppl 3):3 [PubMed]
- Hartmann (1996) Aliment Pharmacol Ther 10(3):359-66 [PubMed]
- Bastaki (2000) J Physiol Paris 94(1):19-23 [PubMed]
- Florent (1997) Eur J Gastroenterol Hepatol 9(2):195 [PubMed]
- Spencer (2000) Drugs 60:321 [PubMed]
XIV. Adverse Effects: General and Short-term
XV. Adverse Effects: Complications of prolonged use
-
Clostridium difficile
- Number Needed to harm: 67 hospitalized patients on PPI for 2 weeks
- http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
- Bavishi (2011) Aliment Pharmacol Ther 34(11):1269-81 [PubMed]
-
Spontaneous Bacterial Peritonitis (SBP) in Cirrhotic patients
- Increased risk (with Odds Ratio 2-3) of SBP, and higher risk than with H2 Blockers
- Campbell (2008) Dig Dis Sci 53(2): 394-8 [PubMed]
- Deshpande (2015) J Gastroenterol Hepatol 28(2): 235-42 +PMID:23190338 [PubMed]
- Hypomagnesemia
- Decreased Bone Mineral Density
- Hip Fracture, wrist Fracture and spine Fracture risk increase (Osteoporosis related Fracture sites)
- Number needed to harm (Hip Fracture): 1263 on PPI for >1 year
- Possibly associated with Vitamin D decreased serum levels
- Targownik (2012) Am J Gastroenterol 107:1361–9 [PubMed]
- Hip Fracture, wrist Fracture and spine Fracture risk increase (Osteoporosis related Fracture sites)
- Vitamin B12 Deficiency
-
Iron Deficiency Anemia
- Decreased iron absorption in the absence of adequate gastric acid
-
Gastric Carcinoma
- Historically, on first release in 1988, bi-annual Gastrin levels were recommended (but soon dispensed with)
- Gastric Cancer risk is low (RR 1.191) with 10 years of continuous use
-
Community Acquired Pneumonia
- Risk increases with PPI dosage
- H2-Blockers also conferred risk, but less than PPI
- Laheij (2004) JAMA 292:1955-60 [PubMed]
- Cardiovascular Disease Risk Factor
-
Dementia
- Association with longterm PPI and Dementia in observational studies
- Gomm (2016) JAMA Neurol +PMID:26882076 [PubMed]
-
Renal Failure
- Acute Kidney Injury increased risk
- Chronic Kidney Disease increased risk of progression
- Serious infections in children (esp. gastrointestinal and ENT infections)
XVI. Safety
- Pregnancy
- Pregnancy Category C: Omeprazole (category B for other agents)
- Initial reports of associated Asthma and allergy with acid suppression
- Subsequent study did not show significant associations
- Noh (2023) JAMA Pediatr 177(3):267-77 +PMID: 36622684 [PubMed]