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PROTON PUMP INHIBITOR AND HISTAMINE 2 RECEPTOR ANTAGONIST USE AND VITAMIN B12 DEFICIENCYTamara Lallier, PharmD, MBAPGY-1 Resident PharmacistNortheast Iowa Family Practice CenterWaverly Health Center
ARTICLE INFORMATION Lam J, Schneider JL, Zhao W, Corley DA.
(December 2013) Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA 310:22, 2435-2442.
Funding: Kaiser Permanente Community Benefit Grant
BACKGROUND Vitamin B12 deficiency
Dementia, neurologic damage, anemia Risk factors
Chronic alcoholismAtrophic gastritisPernicious anemiaH.pylori infectionLong-term use of biguanidesVegetarian/Vegan diet
.
ACID INHIBITORS Proton pump inhibitors
i.e. esomeprazole, omeprazole Histamine 2 receptor antagonists
i.e. ranitidine, famotidine Suppress gastric acid production
PURPOSE
To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States
MEASURED OUTCOMES Risk of vitamin B12 deficiency after >2 years
of PPI or H2RA use Other exposures evaluated:
Number of pills/day Discontinuation of use Duration of use Age Gender Known conditions associated with vitamin B12
deficiency
INCLUSION CRITERIA Case Patients
≥ 18 years old ≥ 1 year Kaiser membership at index date Diagnosed with vitamin B12 deficiency between
1/97-6/11 Diagnosis: Presence of 1 of the following:
Pernicious anemia Other Vitamin B12 deficiency anemia Vitamin B12 deficiency Vitamin B12 deficiency (listed in the Problem List) Abnormally low value of serum vitamin B12 New AND ≥ 6 month supply of injectable vitamin B12
Control Patients Max 10 per 1 Case patient
MEDICATION EXPOSURE Exposure: “Days supplied” variable Exposure duration: time between first and
last prescription (+ days supplied for last rx) Adherence Dose intensity
< 0.75 pills/day 0.75-1.49 pills/day ≥ 1.5 pills/day
“Exposed” patient ≥ 2-year supply of medication prior to index date
CONFOUNDING VARIABLES
Other conditions Health care utilization Other commonly used medications
Estrogen, thiazides, ACE-Is, CCB GERD diagnosis Metformin exposure
PATIENT CHARACTERISTICSCharacteristic Cases (%)
(n=25,956)Controls (%) (n=184,199)
Female 14,909 (57.4) 104,850 (56.9)Male 11,047 (42.6) 79,349 (43.1)
Age < 30 747 (2.9) 6620 (3.6)Age 30-69 12,566 (48.4) 94,829 (51.5)Age 70-89 11,674 (45.0) 77,130 (41.9)Age ≥ 90 969 (3.7) 5,530 (3.0)
≥ 2yr PPI use 3,120 (12.0) 13,210 (7.2)≥ 2yr H2RA use 1,087 (4.2) 5,897 (3.2)No acid inhibitor
use21,749 (83.8) 165,092 (89.6)
RESULTS Presence of other risk factors for vitamin B12
deficiency None: OR 1.65 (95% CI 1.43-1.91) ≥ 1 risk factor: OR 1.50 (95% CI 1.42-1.58)
Age <30 years: OR 8.12 (95% CI 3.36-19.59) > 80 years: OR 1.04 (95% CI 0.96-1.13)
Gender Female: OR 1.84 (95% CI 1.74-1.95) Male: OR 1.43 (95% CI 1.33-1.53)
Race/Ethnicity No significant interaction (P=0.18)
HILL’S CRITERIATemporal relationship
StrengthDose-response relationship
ConsistencyPlausibility
Consideration of alternate explanationsExperimentSpecificityCoherence
CONCLUSION
Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency.
These findings should be considered when balancing the risks and benefits of using these medications.
STRENGTHS
Large size 15 years of data Retrieval of all recorded diagnoses Data for dispensed medication Generalizable control group Ability to evaluate several confounders
LIMITATIONS
Case-control study Asymptomatic screening for patients No information on short-term or intermittent
use Mean daily dose OTC product use Study location not generalizable
CLINICAL RELEVANCE
≥ 2 years of PPIs or H2RAs was associated with vitamin B12 deficiency
Screen symptomatic patients Continue use of these medications for
patients who need them Recommend against higher doses Be aware of symptoms of B12 deficiency
REFERENCES1. Lam J, Schneider JL, Zhao W, Corley DA. (December 2013) Proton Pump
Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA 310:22, 2435-2442.
2. Evatt MLMP, Bobo JK, Kimmons J, Williams J. Why Vitamin B12 Deficiency Should be on Your Radar Screen. Centers for Disease Control and Prevention website. http://www.cdc.gov/ncbddd/b12/index.html. Accessed February 18, 2014.
3. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risks of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57(4):422-428.
QUESTIONS?PROTON PUMP INHIBITOR AND HISTAMINE 2 RECEPTOR ANTAGONIST USE AND VITAMIN B12 DEFICIENCY
Tamara Lallier, Pharm.D., MBAPGY-1 Resident PharmacistNortheast Iowa Family Practice CenterWaverly Health Center