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Proton Pump Inhibitor
Aka: Proton Pump Inhibitor, PPI Therapy, Omeprazole, Prilosec, Lansoprazole, Prevacid, Esomeprazole, Nexium, Pantoprazole, Protonix, Rabeprazole, Aciphex, Dexlansoprazole, Dexilant
- Indications
- Peptic Ulcer Disease
- Gastroesophageal Reflux
- Contraindications
- Hypersensitivity to Proton Pump Inhibitors
- Use with caution in severe liver disease
- Mechanism
- Benzimidazole Proton Pump Inhibitors
- Binds proton pump of parietal cell
- Inhibits >90% of total daily gastric acid production
- PPIs irreversibly bind proton pump
- Pharmacokinetics
- All PPIs have short plasma half life of 1-2 hours
- Effect is delayed 5-7 days until proton pumps are fully blocked
- 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 Esomeprazole Magnesium (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 Esomeprazole Magnesium (Nexium)
- (2014) Presc Lett 21(2): 8
- 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
- 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
- References
- Baird (2015) Am Fam Physician 92(8): 705-14 [PubMed]
- 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)
- Avoid Alcohol, Tobacco, NSAIDs
- Reduce the need for longterm Proton Pump Inhibitor
- 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
- 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
- Precautions: Pregnancy and Lactation
- Pregnancy Category C: Omeprazole
- Pregnancy Category B: Other agents
- Protocol: Discontinuation
- Indications
- Recurrence of GERD or Gastritis symptoms on abruptly stopping Proton Pump Inhibitor
- Use H2 Blocker (e.g. Ranitidine) when symptoms arise on days a Proton Pump Inhibitor is not taken
- 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
- 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
- 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
- Vigneri (1995) N Engl J Med 333:1106-10 [PubMed]
-
Drug Interactions
- Decreased Absorption (due to increased gastric pH)
- Griseofulvin
- Ketoconazole
- Itraconazole
- Iron Salts
- Vitamin B12
- Cefpodoxime
- Enoxacin
- Increased Absorption (due to increased gastric pH)
- Nifedipine (Procardia)
- Digoxin
- Drug level increases specific to Prilosec (CYP 450)
- Carbamazepine (Tegretol)
- Diazepam (Valium)
- Phenytoin (Dilantin)
- Warfarin (Coumadin)
- Methotrexate
- Drug level decreases specific to Prevacid (CYP 450)
- Theophylline
- Drug lowered efficacy specific to Prilosec
- 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
- Juurlink (2009) CMAJ 180(7): 713-8 [PubMed]
- 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
- Melloni (2015) Circ Cardiovasc Qual Outcomes 8(1): 47-55 +PMID: 25587094 [PubMed]
- 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
- Rabeprazole (Aciphex)
- Esomeprazole (Nexium)
- 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]
- Adverse Effects: General and Short-term
- Headache
- Diarrhea
- Abdominal Pain
- Nausea
- 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
- Odds Ratio 3.79
- Markovits (2014) J Clin Pharmacol 54(8): 889-95 [PubMed]
- 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]
- Vitamin B12 Deficiency
- Bradford (1999) Pharmacother 33:641-3 [PubMed]
- Lam (2013) JAMA 310(22): 2435-42 [PubMed]
- Iron Deficiency Anemia
- Decreased iron absorption in the absence of adequate gastric acid
- Gastric Carcinoma
- Originally bi-annual Gastrin levels recommended
- Routine Gastrin levels not currently necessary
- 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
- Shah (2015) PLoS One 10(6):e0124653 +PMID:26061035 [PubMed]
- Dementia
- Association with longterm PPI and Dementia in observational studies
- Gomm (2016) JAMA Neurol +PMID:26882076 [PubMed]
- Renal Failure
- Acute Kidney Injury increased risk
- Antoniou (2015) CMAJ 3(2): E166-71 +PMID:26389094 [PubMed]
- Blank (2014) Kidney Int 86(4): 837-44 +PMID:24646856 [PubMed]
- Simpson (2006) Nephrology 11(5): 381-5 +PMID:17014549 [PubMed]
- Moledina (2016) J Nephrol 29(5): 611-6 +PMID:27072818 [PubMed]
- Chronic Kidney Disease increased risk of progression
- Lazarus (2016) JAMA Intern Med 176(2): 238-46 +PMID:26752337 [PubMed]
- Xie (2016) J Am Soc Nephrol 27(10):3153-63 +PMID:27080976 [PubMed]
- Klatte (2017) Gastroenterol 153(3): 702-10 +PMID:28583827 [PubMed]
- References
- (2012) Prescr Lett 19(3): 14 [PubMed]
- (2013) Prescr Lett 20(5): 30 [PubMed]
- (2001) Med Lett Drugs Ther 43(1103):36-7 [PubMed]
- Ament (2012) Am Fam Physician 86(1): 66-70 [PubMed]
- Vanderhoff (2002) Am Fam Physician 66(2):273-80 [PubMed]