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Transcript of Acid suppression UnAd
The Alosa Foundation
Balanced data about medicationswww.RxFacts.orgBalanced data about medications
Managing dyspepsia:neutralizing the hype• gastroesophageal reflux disease (GERD)• peptic ulcer disease (PUD)• non-ulcer dyspepsia (NUD, or functional dyspepsia)
In the patient with acid-related symptoms:
■■ look for precipitating meds and “red flag” signs or symptoms.
■■ exclude serious non-GI causes.
■■ dealing with H. Pylori -- test patients who have:•ahistoryofulcers,or•ageunder55withnewonsetsymptomsandwithout
obviousGERD.•Ifpositive,treatwith“tripletherapy”for10-14days.
■■ Lifestyle interventions can be useful in controlling symptoms.
■■ Prescribe a medication if symptoms persist:•Protonpumpinhibitors(PPIs)areveryeffective,butmay
notbenecessaryinallpatients.•AlternativesincludeH2andantacidsblockers.
2
Initial assessment1-5
1. Look for precipitating medications, including aspirin, NSAIDs, anticholinergic drugs, corticosteroids, theophylline, dopaminergic agents, oral bisphosphonates, and calcium channel blockers.6
2. Exclude serious non-GI causes of dyspepsia, such as: • coronary artery disease • aortic dissection • pericarditis • pulmonary embolism
3. Look for “red flag” signs or symptoms – alarm features that might suggest cancer, stricture or severe ulceration. If present, refer for endoscopy:
• recurrent vomiting • hematemesis • dysphagia • GI bleeding • abdominal mass • anorexia • early satiety • anemia • change in bowel habits • odynophagia • hepatomegaly • unexplained weight loss • lymphadenopathy • previous GI malignancy or ulcer
An approach to the patient with non-GERD dyspepsia5
Dyspepsia
Age > 55 or “red flags” Age ≤ 55 No “red flags”
Consider Endoscopy
Figure reproduced with permission from: Talley NJ, Vakil N. Guidelines forthe management of dyspepsia. Am J Gastroenterol. Oct 2005;100(10):2324-2337.
H. Pylori prevalence< 10%
H. Pylori prevalence≥ 10%
PPI trial Test and treatfor H. pylori
Consider Endoscopy
Consider Endoscopy
Test and treatfor H. pylori PPI trial
Symptoms persist
Symptoms persist
Symptoms persist
Symptoms persist
3
Non-prescription therapies often work well• avoid acidic foods or those that precipitate symptoms (e.g., citrus, onions, tomatoes); •avoid products that increase acid production or can damage mucosal defenses (NSAIDs,
alcohol, tobacco, caffeine).
H. pylori testing1,3,5
Evaluate patients with:•active gastric or duodenal ulcer;•history of gastric or duodenal ulcer not yet treated for H. pylori infection;•new-onset dyspepsia in adults ≤ 55 years without obvious GERD and without red flag
signs or symptoms, in populations with high ulcer or H. pylori prevalence (e.g., immigrant populations);
•patients who do not respond to treatment.
How to test:For most patients:
•urea breath test and stool antigen test are accurate non-invasive diagnostic tools, but are cumbersome to obtain in routine practice.
•serum antibody testing has lower sensitivity and specificity, but it is commonly ordered because of its convenience.
If the patient undergoes endoscopy, a biopsy is the most accurate test.
If test is positive for H. Pylori, treat with triple therapy for 10-14 days:•PPI, standard dose twice daily, and•amoxicillin* 1000 mg twice daily, and•clarithromycin 500 mg twice daily.
*Metronidazole (500 mg twice daily) should be substituted for amoxicillin in patients with penicillin allergy.
Single-prescription triple therapy (Prevpac) is convenient, but more expensive than individual medications.
For Patients With Acid-Peptic Disease:
4
For patients with GERD:2,4,5,7
:
Lifestyle interventions Endoscopy
No (majority of patients)Yes
Short course of PPI, or as-needed
H2 blocker or antacid
Heartburn and/or acid regurgitation as the predominant or frequent (> 1 episode per week) presenting complaint
“red flag” features?(a minority of patients)
Endoscopy- negative re�ux
disease
Esophagitis
For further management, see figure below, “If additional treatment is required”
High dose PPIfor 4-8 weeks
if symptoms persist
Manage other abnormal endoscopic findings based on the diagnosis.
Lifestyle modification can greatly help reduce reflux:•eliminate substances that reduce tone in the lower esophageal sphincter (caffeine, alcohol,
tobacco, mint, chocolate, fatty or fried foods);•avoid large meals right before bedtime;•elevate the head of the bed;•avoid tight clothing that constricts the abdomen;•do not recline within 2-3 hours after a meal;•lose weight if overweight.
5
Although PPIs are often taken on an as-needed basis, they do not work well in this way because they can require more than 24 hours to reduce acid production and achieve symptom relief. By contrast, antacids are effective within minutes and H2 blockers work within an hour.
Avoid “as-needed PPI’’
Time required for symptom relief
0
Hours
0 5 10 15 20 25 30
PPIs
H2 blockers
Antacids
30-60 minutes
5-20 minutes
>24 hours
PPIs cause more adverse effects than H2 blockers8...•headache•diarrhea•abdominal pain
...and PPIs carry a risk of more serious adverse effects:•clostridium difficile infection•fractures•interstitial nephritis•pneumonia•potentially reduced efficacy of clopidogrel•rebound acid hyper-secretion when PPI stopped.
6
Who really needs a PPI?
Patient taking PPI
e.g. omeprazole 20mg twice daily
Reduce the doseby half for 2 weeks
e.g. omeprazole 20mg once daily
Stop the PPI
If needed, use:• a generic or
OTC H2 blockersuch as ranitidine(Zantac)
• an antacid
Long term
Slowly reduce thedose of H2 blockeror antacid to thelowest amountneeded to controlsymptoms
Only a few conditions require long-term use of PPIs:
•GERD with esophagitis, ongoing symptoms, or complications such as Barrett’s esophagus•recurrent Peptic Ulcer Disease•Zollinger-Ellison Syndrome
For everybody else:•Re-evaluate after 4-8 weeks•Use step-down therapy •Taper PPIs and educate about using H2 blockers and/or antacids.
Plan on tapering and then discontinuing PPIs in patients with:
•GERD without esophagitis if symptom-free after 4 weeks of therapy•Peptic Ulcer Disease if symptom-free after 4-8 weeks of therapy and H. pylori eradication•Non-Ulcer Dyspepsia if symptom-free after 4-8 weeks of therapy
This tapering regimen, including the use of as-needed H2 blockers and antacids, can control rebound symptoms and provide the best chance of successfully stopping PPIs.
7
If additional treatment is required1-5…
GERD(with esophagitis)
GERD(without esophagitis)
• high dose PPI for 4-8weeks (as per algorithm above), then:
(i) long-term daily PPI therapy titrated down to the lowest e�ective dose based on symptom control, or
(ii) long-term daily PPI at maintenance doses for patients with erosive disease
Peptic Ulcer Disease Non-Ulcer Dyspepsia
If additional treatment is required…1-5
• short course of PPI, oras-needed H2 blockeror antacid (as per algorithm above), then:
(i) if symptoms resolve, taper down dose of PPI. Change to H2 blocker or antacid and taper down to lowest e�ective daily or prn dose, or
(ii) if symptoms persist, standard dose PPI once or twice daily
• stop smoking and avoid excessive alcohol
• discontinue aspirin/NSAIDS if possible; if these agents need to be continued, add a PPI or misoprostol
• treat bleeding or other complications
• test and treat for H. pylori
• PPI for 4-8 weeks
• con�rm eradication of H. pylori
• if H. pylori still present, make a second attempt at eradication
if symptoms persist or a second attempt at H. pylori eradication fails, consider referral
• PPI or H2 blocker for 4-8 weeks
• consider testing and treating for H. pylori
• if no response, consider prokinetic agent, antidepressant therapy, cognitive behavioral therapy, or hypnotherapy
if symptoms persist, consider specialist referral
If symptoms persist, consider specialist referral for:• endoscopy• manometry• pH monitoring• surgery
Choosing among medicationsThe different PPIs have similar efficacy, but big differences in economic burden.9-13 The costs of a 30-day supply of commonly used daily doses of acid-neutralizing/suppressive medications are provided in the figure on the following page.
References: 1. Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. Aug 2007;102(8):1808-1825. 2. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology. Oct 2008;135(4):1383-1391. 3. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010;362(17):1597-1604. 4. Talley NJ. American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology. Nov 2005;129(5):1753-1755. 5. Talley NJ, Vakil N. Guidelines for the management of dyspepsia. Am J Gastroenterol. Oct 2005;100(10):2324-2337. 6. Katelaris P, Holloway R, Talley N, Gotley D, Williams S, Dent J. Gastro-oesophageal reflux disease in adults: Guidelines for clinicians. J Gastroenterol Hepatol. Aug 2002;17(8):825-833. 7. Kahrilas PJ. Clinical practice. Gastroesophageal reflux disease. N Engl J Med. Oct 16 2008;359(16):1700-1707. 8. Comparative effectiveness of management strategies for Gastroesophageal Reflux Disease. AHRQ Pub No. 06-CH003. 1 Dec 2005. Available at: http://effectivehealthcare.ahrq.gov/ehc/products/1/42/GERDExecSum.pdf. 9. Carswell CI, Goa KL. Rabeprazole: an update of its use in acid-related disorders. Drugs. 2001;61(15):2327-2356. 10. Langman MJ. Which PPI? Gut. Aug 2001;49(2):309-310. 11. Stedman CA, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther. Aug 2000;14(8):963-978. 12. Vanderhoff BT, Tahboub RM. Proton pump inhibitors: an update. Am Fam Physician. Jul 15 2002;66(2):273-280. 13. Welage LS, Berardi RR. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc (Wash). Jan-Feb 2000;40(1):52-62; quiz 121-123.
Additional references documenting these recommendations are provided in the evidence document accompanying this material, or available at
www.RxFacts.orgThis material was produced by Leslie Jackowski, B.Sc., M.B.B.S., Senior Clinical Consultant, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital; Niteesh K. Choudhry, M.D., Ph.D., Associate Professor of Medicine, Harvard Medical School; Michael A. Fischer, M.D., M.S., Assistant Professor of Medicine, Harvard Medical School; Danielle Scheurer, M.D., M.Sc., F.H.M., Assistant Professor of Medicine, Medical University of South Carolina; and William H. Shrank, M.D., M.S.H.S., Assistant Professor of Medicine, Harvard Medical School. Series editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs Avorn, Choudhry, Fischer, and Shrank are all physicians at the Brigham and Women’s Hospital in Boston. Dr. Scheurer is a physician at the Medical University of South Carolina. None of the authors accepts any personal compensation from any drug company.
The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Rx Foundation.
This material is provided by The Alosa Foundation, a nonprofit education organization which is not affiliated in any way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient’s clinical condition.
The Alosa Foundation
Balanced data about medications ©2011 Alosa Foundation, all rights reserved. December 2011
cimetidine 800mg
famotidine 40mg
nizatidine 300mg
ranitidine 300mg
esomeprazole 20mglansoprazole 30mg
omeprazole 20mg
pantoprazole 40mg
rabeprazole 20mg
Antacids (e.g., OTC magnesium/aluminum hydroxides)
$- $50 $100 $150 $200 $250 $300Cost in dollars
Costs of a 30-day supply of acid-neutralizing/suppressive medications
Prices from www.drugstore.com, www.epocrates.com, and several dispensing pharmacies, December 2011.
$2
Tagamet, $47 generic, $4 prescription Pepcid, $114
OTC Pepcid, $20 generic, $4
Axid, $170 generic, $54 prescription Zantac, $241
OTC ranitidine, $12 generic, $4
Nexium, $196 Prevacid, $170 Prevacid Solutab, $170
OTC Prevacid, $37 prescription Prilosec, $196 generic OTC Prilosec, $20 Protonix, $170 generic, $16
Aciphex, $219