PPI OVERUSE: CAN YOU STOMACH IT? MARCUS COOKSEY, MSN, FNP - - PDF document

10/12/2015 1

PPI OVERUSE: CAN YOU STOMACH IT?

MARCUS COOKSEY, MSN, FNP

Appropriate Prescribing & Safety Concerns

SCENERIO

Patient med refill request: Omeprazole 20mg q12 hrs #60

 67 yo male  CAD w/ 2 stents  HTN  OA of knees  Dyslipidemia

CURRENT OTHER MEDS

 Chlorthalidone  Isosorbide Mononitrate  Atorvastatin  Clopidogrel  Oxybutynin  Amlodipine  Naproxen PRN

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YOU CHECK THE CHART…..

 Nothing GI on problem list . . .  No notes in chart about abdominal pain  Patient has not been seen in clinic since

2013

 Omeprazole on med list since 2006

SO, WHAT DO YOU DO?

• A. Refill the 60/month w/ another 11 refills…
• B. Deny the refill, requiring the patient be seen
• C. Refill only 60 tabs, NO refills, requiring an

appointment for any future refills

• D. Deny the refill and send an Rx for Ranitidine

instead

SO, WHY AM I HERE?

 Proton pump Inhibitors (PPIs) make up over 50%

• f the GI drug market in the USA

 Literature suggests that 2/3 of PPI usage may be

inappropriate, lacking in evidence for utility.

 Adverse effects include infections (PNA,

C diff, SIBO), decreased vitamin/mineral absorption, fractures, and possibly MI’s?

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GOALS OF PRESENTATION

 Review the literature of safety concerns for

PPI’s.

 Discuss differential diagnosis and

alternative treatment modalities.

 Describe how to taper and discontinue PPI’s,

• r give informed consent for patients who

desire to continue them. WHAT DRUGS ARE WE TALKING ABOUT?

Drug Formulations OTC Formulary (As of 11/5/2014)

Rabeprazole (Aciphex) Tablets & sprinkles NO  Omeprazole (Prilosec) Capsules, packets & suspensions Yes CO-D, CO-OHP, FC-D, FC-D, MCHD, MODA-OHP Esomeprazole (Nexium) Capsules, packets & IV No FC-D (higher co-pay) Lansoprazole (Prevacid) Capsules, solutab & suspension Yes CO-D, MODA-OHP Dexlansoprazole (Dexilant) Capsules No FC-D (higher co-pay) Pantoprazole (Protonix) Packet, solution & tabs No CO-D, CO-OHP, FC-D, FC-D, MCHD, MODA-OHP

PPI FINANCIALS….. THE BIG BUCKS!!!!!

 >$2.5 million for PPI’s for OHP in 2014  > 20 million Americans take PPI regularly  In 2013, U.S. spent $6.1 BILLION dollars on Nexium

(esomeprazole) alone!

 Cost of side effects? The Oregon state drug review, August 2015, Volume 5, Issue 5 pharmacy.oregonstate.edu/drug-policy/newsletter

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MEDICARE 2013 TOP TEN DRUG CLAIMS

Rank Drug Claims #’s 1 Lisinopril 36k 2 Simvastatin 36k 3 Levothyroxine 35k 4 Hydrocodone-acetaminophen 34k 5 Amlodipine 34k 6 Omeprazole 32k 7 Atorvastatin 26k 8 Furosemide 26k 9 Metformin 22k 10 Metoprolol 21k

https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheets-items/2015-04-30.html

Rank Drug Cost in $ Billions

1 Esomeprazole (Nexium) $2.5 2 Fluticasone Propionate & Salmeterol (Advair) $2.2 3 Rosuvastatin (Crestor) $2.2 4 Aripiprazole (Abilify) $2.1 5 Duloxetine (Cymbalta) $1.9 6 Tiotropium (Spiriva) $1.9 7 Memantine (Namenda) $1.5 8 Sitagliptin (Januvia) $1.4 9 Insulin Glargine (Lantus Solostar) $1.3 10 Lenalidomid (Revlimid) $1.3

MEDICARE 2013 DRUG COSTS

https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheets-items/2015-04-30.html

“One nation, under GERD”

Niall Brenan, Medicare data officer

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IS DYSPEPSIA THE NEW NORM?

 Dyspepsia: also known as

indigestion (bloating, belching, nausea, pain, heartburn)

 Common: everyone

experiences at some point.

Sources of dyspepsia

Why USE PPIs?

 PPIs are often started inpatient, ED, specialist office,

patients OTC w/ no clear indication.

 Lack of assessment for ongoing therapy or if current dose is

the lowest effective dose needed.

 Assessing and discussing lifestyle and psychological factors

is difficult in 15 minutes!

 Rebound hypersecretion reinforces the need for daily PPI,

>50% of pts who abruptly discontinue. PPIs after 2-3 months of use will develop rebound hypersecretion.

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INFANTS & GERD: DAILY PREVALENCE

Age in months

Nelson et. Al, 1997 Arch Pediatric Adolescent Med

%

Infant 5kg 180 ml bottle

=

Adult 80kg 3 liter

PPI’s FOR CHILDREN WITH GERD

A LITERATURE REVIEW: RCT’s & CROSSOVER STUDIES:

 Infants: 4/5 studies showed no difference in PPI TX

• vs. Placebo

 Children/Adolescents: No difference PPI TX vs.

Controls (ranitidine or alginates)

 Children w/ Histological abnormalities: No

difference PPI TX vs. Controls

Van der Pol et. Al, 2011 Pediatrics Volume 127, number 5

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VITAMIN & MINERAL ABSORPTION

Malabsorption of nutrients that require gastric acidity: calcium carbonate, iron, magnesium and vitamin B-12

 Clinical relevance of this interaction is not known, some experts and

literature recommend using calcium citrate for calcium supplementation when patient is on chronic PPI as calcium citrate not effected by gastric acidity.

 Reduced magnesium absorption may be of concern in patients on

diuretics or on digoxin therapy. Symptoms of hypomagnesemia: muscle cramps, heart palpitations, dizziness, tremors and seizures

FRACTURES AND BMD w/ PPI

 Long-term PPI use is associated with a 25% increase in overall

fracture risk in postmenopausal women.

 Risk of hip fracture is only increased in patients with other risk

• factors. NNH=1200

 This risk should not prevent use of PPI in patients with

• steoporosis when there is an indication but evaluate risk,

prescribe lowest effective dose, and discuss calcium/vitamin D supplementation.

 No documented effect on bone mineral density.

Gray, et al. 2010. Arch Int Med 170: 765–771.

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CLOSTRIDIUM DIFFICILE GASTROENTERITIS

2-fold increase in risk for C. diff

infections w/ PPI use

NNH = 533 inpatients and risk of

recurrence is 42% in those who are taking a PPI.

H2RAs also increase risk, but to a

lesser extent

Deshpande et. Al. 2012, Clinical Gastroenterology and Hepatology

PPIs & INFECTION RISKS

Small intestinal bacterial overgrowth (SIBO):

 Association only found w/ aspirate diagnosis

Pneumonia:

 Greatest risk being for inpatients on vents  Data has led to conflicting results regarding risk for CAP while on PPIs,

some data showing a NNH = 226 when PPIs are used for 5 months.

 Associated w/ short term PPI use and NOT long-term PPI therapy

Peritonitis



PPI use in patients with cirrhosis was independently associated with higher risk for infections (peritonitis, sepsis, others)

Lo & Chan: 2013, Clinical Gastroenterology and Hepatology Sarkar M, Hennessy S, Yang Y-X. Ann Intern Med. 2008;149(6):391-398 O’Leary et. Al. 2015, Clinical Gastroenterology and Hepatology

PPI’s & Myocardial Infarction?

 Large data mining study showed small increase in

MI w/ PPI’s use (>2 million people, 2 distinct data sets)

 Incidence of death from MI doubled w/ long-term

PPI use

 Independent of other variables (smoking, age,

disease comorbidity, clopidogrel use, ect.)

 No association with H2 blockers

Shah et. al, 2015. PLOS one

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PPI’s & Myocardial Infarction?

Shah et. al, 2015. PLOS one

PPI’s & Myocardial infaction?

 Various theories:

no smoking gun

 Interction w/ clopidogrel

(Plavix) activating isoenzyme?

 Black box warning about

combining PPI w/ clopidogrel

https://www.youtube.com/watch?v=OBRKP

• APXEQ

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REBOUND HYPERSECRETION

REBOUND HYPERSECRETION

 Higher pH during treatment appears to stimulate

hypersecretion of HCl upon PPI withdrawal

 Increased Gastrin (hormone which stimulates HCl

production) during PPI tx

 Avoid rebound symptoms by tapering PPI q1-2 wks

to lowest available dose and then every other day therapy for 1-2 weeks

Reimer et al. Gastro 2009; 137: 80-87 Niklasson et al. Am J Gastro 2010; 105: 1531-37

FDA APPROVED CONDITIONS FOR PPI TREATMENT

APPROVED

 GI ulcers  H. Pylori  Hypersecretory conditions

(Zollinger Ellison)

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FDA NOT APPROVED CONDITIONS FOR PPI TREATMENT

NOT APPROVED (but we do it anyway)

 Erosive esophagitis  GI ulcer prophylaxis with

NSAIDs

 Dyspepsia  Asthma Symptoms  Functional abdominal

pain

OHP PPI COVERAGE CHANGES

Effective July 1st, 2015

 Omeprazole or Pantoprazole <8 weeks, no TAR  >8 weeks needs prior authorization  H2 blockers: Ranitidine preferred and no limitations  Current patients on PPI will have 1 year of automatic approval The Oregon state drug review, August 2015, Volume 5, Issue 5 pharmacy.oregonstate.edu/drug-policy/newsletter

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ALTERNATIVE DIAGNOSIS

 Stress?  Cultural?  Hypochlorhydria: Normal gastric pH 1.5-2.5

PPI makes symptoms of belching or gas in upper GI worse. Can check pH on EGD

 Post-cholycystectomy syndrome: lack of bile prevents fat

digestion and indigestion. Consider Ox bile supplement w/ meals.

 DM Gastroparesis: a damaging of nerves for GI motility.

Think as PN of autonomic system.

 Eosinophilic Esophagitis: allergen mediated?

ALTERNATIVES TO PPIs

Lifestyle: mindfulness in eating (cephalic, oral-

mastication, and then lower GI digestion)

Diet: avoid acid provoking foods Marshmellow Root: cold extraction, coats mucous

membranes

Apple Cider Vinegar (1 Tablespoon in 8 ounces

• f water) or betaine HCl prior meals for

hypochlorhydria

ALTERNATIVES TO PPIs

Alginates (Gaviscon, ect.) : from algae cell

walls; creates gel to thicken liquid and coat esophagus

Antacids: magnesium hydroxide, calcium (e.g.

milk), bismuth sulfate, magnesium 400mg

TCA’s (Desipramin, Amitriptyline) for functional

dyspepsia

H2 blockers (Ranitidine, Famotidine)

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THE 5 R’s

 Remove: stressors, parasites, food intolerances  Replace: digestive enzymes, hydrochloric acid,

bile acids that may be compromised by disease/surgery/lifestyle.

 Reinoculate: lactobacillus, sacchromyces boulardii

(Red Star Yeast 1 tsp x2/day)-foods best source, prebiotics w/ inulin

 Repair: add key nutrients  Rebalance: sleep, stress, exercise

PEARLS

 PPIs are 4th line treatment for

GERD/dyspepsia

 Taper: for 1-2 weeks take PPI every other

day +/- H2-blocker on the off days

 Informed consent if continuing long-term PPI  Get pickled: introduce fermented foods back

into the diet

REFERENCES



Aseeri, M., Schroeder, T., Kramer, J. and Zackula, R. (2008) Gastric acid suppression by proton pump inhibitors as a risk factor for Clostridium-difficile-associated diarrhea in hospitalized patients. Am J Gastroenterol 103:2308–2313



Deshpande et. Al. Association between proton pump inhibitor therapy and clostridium difficile infection in a meta-analysis. Clinical Gastroenterology and Hepatology. 2012; 10: 225-233.



Fass, R. Alternative therapeutic approaches to chronic proton pump inhibitor treatment. Clinical Gastroenterology and Hepatology. 2012 10:338-345.



Forgacs, I. and Loganayagam, A. (2008) Overprescribing proton pump inhibitors is expensive and not evidence based. BMJ 336: 2–3.



Gray, S.L., LaCroix, A.Z., Larson, L., Robbins, J., Cauley, J.A., Manson, J.E. et al. (2010) Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women. Arch Int Med 170: 765– 771.



Heidelbaugh, J.J., Goldberg, K.L. and Inadomi, J.M. (2009) Adverse risks associated with proton pump inhibitors: a systematic review. Gastroenterol Hepatol 5: 725–734.



Heidelbaugh, J.J. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical

• implications. Ther Adv Drug Saf. 2013 Jun;4(3):125-33



Hess, Hoenderop, et. al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012; 36: 405–413

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REFERENCES cont.



Vakil N. Prescribing PPIS, is it time to pause and rethink?. Drugs 2012; 72 (4): 437-445



Mazer-Amirshahi M, et al. Rising rates of proton pump inhibitor prescribing in US emergency

• departments. Am J Emerg Med 2014 Jun;32(6):618-22



Nelson et. Al. Prevalence of symptoms of gastroesophageal frefulx during infancy. Arch Pediatric Adolescent med. 1997 Jun 15; 151 (6): 569-72



Reimer et. Al. Proton pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009; 137:80-87.



Sarkar M, Hennessy S, Yang Y-X. Proton-pump inhibitor use and the risk for community- acquired pneumonia. Ann Intern Med. 2008;149(6):391-398



Shah et. Al. Proton pump inhibitor usage and the risk of myocardial infaction in the general

• population. PLOS one. 2015.



Van der Pol. Efficacy of propton pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011; Vol 127, Number 5.