Download Management of Uncomplicated GERD in Adult Patients

JOURNAL CE
Management of Uncomplicated GERD in Adult Patients
ACPE UAN: 0171-9999-15-037-H01-P
Kayce Shealy, PharmD, BCPS, BCACP, CDE, Assistant Professor, Department of Pharmacy Practice
Director, Center for Entrepreneurial Development, Presbyterian College School of Pharmacy
Jennifer N. Clements, PharmD, BCPS, CDE, BCACP, Interim Chair and Associate Professor
Department of Pharmacy Practice, Presbyterian College School of Pharmacy
Objective:
At the conclusion of this knowledge-based activity,
the pharmacist will be able to:
• Review the pathophysiology and common clinical
presentation of gastroesophageal reflux disease
(GERD).
• Evaluate diagnostic criteria for GERD for adult
patients and describe current treatment guidelines
from the American College of Gastroenterology
(ACG).
• Compare and contrast treatment modalities available for the management of uncomplicated GERD
in adult patients.
• Recognize the role of the pharmacist in managing
uncomplicated GERD in adults.
Objective: To review the treatment of uncomplicated
gastroesophageal reflux disease (GERD) in adult patients.
Data sources: PubMed using search terms gastroesophageal
reflux disease, diagnosis, erosive esophagitis, antacids,
histamine-2 receptor antagonists, proton pump inhibitors,
and current treatment guidelines.
Data synthesis: Gastroesophageal reflux disease is a
common gastrointestinal disorder for both pediatrics
and adults. The backflow of contents from the stomach
into the esophagus can lead to common symptoms
such as heartburn, regurgitation, and acidic taste.
Gastroesophageal reflux disease is divided into esophageal
or extraesophageal syndromes, and then further depending
on the presence of esophageal injury. Many exacerbating
factors have been identified, including certain foods,
pregnancy, being overweight or obese, and some
medications.
There are many treatment options available for use in the
medical management of GERD in adult patients. These
Palmetto Pharmacist • Volume 55, Number 4
options include antacids, histamine-2 receptor antagonists
(H2RAs), and proton pump inhibitors (PPIs). Guidelines
for both adult and pediatric patients have recently been
published to provide guidance on the treatment of GERD
in these populations. For adult patients, the preferred
treatment strategy includes PPI therapy in conjunction
with lifestyle modifications.
Conclusion: Pharmacists, regardless of setting, are likely
to encounter patients who suffer from GERD. It is
important to be aware of the updated treatment guidelines,
as well as the different medications available, in order to
ensure optimal patient care is provided.
Keywords: gastroesophageal reflux symptoms,
gastroesophageal reflux disease
Introduction.
Gastroesophageal reflux disease (GERD) is a relatively
common gastrointestinal disorder.1 In 2009, there were
approximately 9 million outpatient visits for GERD
in the United States (US) alone.1,2 Gastroesophageal
reflux disease is caused by the backwards flow of
stomach contents, or acid reflux, into the esophagus,
leading to symptoms such as heartburn and potentially
esophageal damage.3 Gastroesophageal reflux symptoms
(GERS) such as heartburn or reflux may occur without
being classified as GERD. According to the Montreal
definition, GERD develops once these symptoms become
troublesome and affect the patient’s quality of life.4 It
is categorized into esophageal or extraesophageal
syndromes, and then further divided based upon the
presence of esophageal damage.4
The reflux of contents back into the esophagus may
be due to many factors, including dysfunction in the
lower esophageal sphincter (LES).5 The LES is an
area of smooth muscle at the end of the esophagus that
protects contents from the stomach, including gastrin
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and pepsin, from flowing into the esophagus. Back flow
of these acidic enzymes can lead to damaged tissue in
the esophagus or aspiration. During periods of eating
and swallowing, the LES also acts as a one-way valve
to prevent the passage of food or other stomach contents
back into the esophagus. The LES does, however, have
transient episodes of relaxation in healthy adults where
the backflow of stomach contents may occur, but these
episodes are usually symptom-free.2 Changes in the gastroesophageal pressure gradient may
also lead to the inappropriate relaxation of the LES.5 This
may be the result of either increased intra-abdominal
pressure or reduction in pressure at the LES. Increased
pressure is present during pregnancy and among
overweight or obese people.1 Changes in anatomy, such
as presence of hiatal hernia, may also contribute to the
development of GERD. Hiatal hernias may lead to the
presence of an acid pocket much closer to the esophagus
than normal, allowing more reflux to occur. Delayed
gastric emptying has also been linked to the development
of GERD and related symptoms. Factors that delay or
prolong gastric emptying may contribute to or exacerbate
symptoms.5 The presence of Helicobacter pylori (H.
pylori), though, has no effect on the development or
severity of GERD.1,5 Factors that may exacerbate
symptoms related to GERD are presented in Table 1. The true prevalence of GERD worldwide is not
completely clear, although it appears to be higher in
Europe and North America.3 It has been reported that the
prevalence of GERD in patients of all ages in these areas
is anywhere from 10-30%, while approximately 5-6% of
the Asian population may have GERD.3 Clinical Presentation
When encountering a patient with possible GERD,
it is important to thoroughly assess the patient’s
symptoms. Based on an individual’s symptoms, GERD
can be divided into two main categories - esophageal or
extraesophageal conditions. Esophageal conditions can be
further categorized as symptomatic syndromes (i.e. typical
reflux, reflux chest pain syndrome) or esophageal injury
(i.e. Barrett’s esophagus, adenocarcinoma). Barrett’s
esophagus is a long-term complication of GERD and
is associated with an increased risk of esophageal
cancer. Extraesophageal conditions may have proposed
associations with other problems, such as sinusitis and
pharyngitis. Extraesophageal conditions can also have
established associations, such as asthma with reflux.1,4,6,7 30
A pharmacist would most likely encounter a patient when he/
she has experienced troublesome symptoms. Troublesome
symptoms may interfere and affect the patient’s normal
activities and/or quality of life. There are three classic
symptoms of GERD – heartburn, regurgitation, and
acidic taste – which are defined in Box 1.6,7 In addition
to esophageal symptoms, a patient should be assessed
for possible extraesophageal symptoms. Questions may
include do you have a chronic cough? Have you noticed or
experienced asthma-like symptoms? Have you experienced
other symptoms, such as recurrent sore throat, laryngitis, or
hoarseness? In the updated American College of Gastroenterology (ACG)
guidelines, troublesome dysphagia - formerly referred to as
alarming symptoms - should be determined.7 These symptoms
include dysphagia, odynophagia (i.e. painful swallowing with
or without dysphagia), bleeding, weight loss, choking, chest
pain, and epigastric mass. If a pharmacist encounters a patient
with these troublesome symptoms, then the patient should be
instructed to seek immediate medical attention with a referral
for invasive testing. For example, a patient complaining of
possible GERD-related chest pain may be experiencing angina
pectoris (i.e. squeezing sensation in sternal area). In addition,
odynophagia is a rare symptom of GERD, but may indicate
the presence of an esophageal ulcer.7
A patient should be encouraged to identify aggravating factors,
leading to current GERD symptoms. For example, increased
intra-abdominal pressure (i.e. tight-fitting clothes, pregnancy)
could cause the classic symptoms of GERD. Certain types
of food (i.e. chocolate or peppermint) can reduce the lower
esophageal sphincter tone. Other aggravating factors could
be recumbency or gravity, reduced gastric motility, and direct
mucosal irritation. A patient should be given a diagnosis of
GERD in a timely manner in order to begin treatment and
prevent long-term complications, such as erosion, strictures,
obstruction, and Barrett esophagus.7
After a thorough patient interview has been completed,
the frequency and severity of a patient’s GERD symptoms
should be assessed in order to classify the patient’s
condition. In addition, the presence of erosive esophagitis
on upper endoscopy may need to be determined before
initiating treatment. The mild and/or intermittent
classification is defined as symptoms occurring less than
two times (or episodes) per week and no evidence of erosive
esophagitis.1,4,7 If a patient has mild or intermittent GERD,
then the individual may experience symptoms following
meals. The severe and/or frequent classification is defined
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as symptoms occurring more than two times (or
episodes) per week and there is presence of erosive
esophagitis.1,4,7 A patient with severe or frequent GERD
may experience the classic symptoms following meals,
during the day and/or at bedtime. Refractory GERD is
continual symptoms despite adequate trial of once-daily
PPI therapy. A patient with refractory GERD should be
referred to a gastroenterologist.1,4,7
Diagnostic Criteria
Table 2 lists possible diagnostic tests for
adults and pediatric patients, along with the purpose of
each test. For more details, please refer to the specific
guidelines for GERD in these patient populations.2,6,7
Based on the ACG guidelines, there are specific
diagnostic tests recommended to confirm GERD. Any
patient with symptoms resembling troublesome
dysphagia (see Box 1) should be referred for an
endoscopy due to the possibility of complications,
such as Barrett’s esophagus. An esophageal reflux
monitoring test is another diagnostic test and can be
completed if (1) non-erosive GERD is suspected, (2)
patient has refractory GERD after an adequate trial
of proton pump inhibitors, or (3) there is an uncertain
diagnosis. If a patient has refractory GERD and surgery
is an option, then manometry should be completed
prior to the procedure. However, this test is not useful
in confirming the diagnosis of GERD. The ACG
guidelines do not recommend barium testing, biopsies,
or screening for Helicobacter pylori to determine and/
or confirm the diagnosis of GERD.6,7 A clinical diagnosis
of GERD can be made if the patient presents with the
classic symptoms, in which empiric therapy can be
initiated. The patient may also be evaluated for noncardiac causes of GERD. A differential diagnosis should
be considered, evaluating any cardiac cause first, then
gastrointestinal cause.6,7 Treatment Recommendations:
For adult patients, the primary set of guidelines is
published by the ACG. In 2008, the ACG guidelines
provided recommendations and additional information
on 12 broad questions based on clinical practice and
scenarios.6 These questions ranged from diagnosis to
pharmacologic therapy to surgical options for patients
with GERD.6 In 2013, the ACG guidelines were updated
to provide strong or conditional recommendations based
on the level of evidence (i.e. high, moderate, or low).7
In comparison, the 2013 guidelines provide clarity to the
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diagnosis of GERD. This set of guidelines had similar
recommendations for the nonpharmacologic interventions
and pharmacologic therapy, but provide a specific
duration for proton pump inhibitor (PPI) administration
(i.e. 8 weeks). Due to recent evidence, the 2013 ACG
guidelines elaborated on the long-term management of
GERD with proton pump inhibitors (PPIs).7
Nonpharmacologic Interventions
Lifestyle modifications should be included in the
treatment for GERD. The 2013 ACG guidelines
recommend weight loss to ameliorate symptoms,
especially among patients who are overweight, obese
or have experienced recent weight gain.7 In addition,
elevating the head of the bed can be recommended, as
lying down can precipitate GERD symptoms.7 If patients
are experiencing symptoms later in the evening or during
the night, the ACG guidelines recommend avoiding meals
within 2-3 hours of bedtime.7 These recommendations
are based on low to moderate evidence because these
interventions have been investigated in mostly casecontrol studies, and only bed elevation has been
investigated in a randomized, controlled trial.7 While
avoiding food triggers and reducing consumption
of tobacco and alcohol is commonly encouraged by
health care providers, there is little literature to support
the notion that these dietary restrictions may actually
improve GERD symptoms. Several trials are available
that demonstrate an effect on LES pressure for some of
these foods or products, including tobacco, chocolate, and
carbonated beverages, but there are also several trials that
suggest consuming these had no effect. Likewise, there
are a handful of trials that show avoiding or reducing
the consumption of these common dietary and lifestyle
triggers has no effect on symptoms, LES pressure, or
esophageal pH.7 For this reason, routine elimination or
avoidance of certain foods such as chocolate, spicy foods,
caffeine, or alcohol are not recommended as part of the
patient care plan. Surgery may be an effective option for patients needing
long-term management. The ACG suggests surgery
be considered for patients who wish to discontinue
medications or who are nonadherent, experience
undesirable adverse effects, or have GERD or
esophagitis that is refractory to medical management.7
However, it should not be considered for symptomrelief only in patients who have had no response to
PPI treatment.7,9 Surgery has been shown to be more
successful and effective long-term in patients with typical
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GERD-like symptoms and also have responded well to
PPI treatment. If patients’ symptoms fail to respond to
PPI therapy, including high-dose, they are less likely
to experience symptomatic relief with surgery. Before
considering surgery for these non-responding patients,
other causes of these symptoms should be evaluated by ear,
nose, and throat (ENT) specialists, as well as pulmonary
and allergy specialists. Obese patients may benefit from
bariatric surgery, especially gastric bypass.7
Pharmacologic Interventions
There are several options available for the medical
management of GERD. These include antacids, histamine
receptor antagonists (H2RAs), and PPIs. Proton pump
inhibitors are the preferred treatment for patients who
suffer from GERD with erosive esophagitis. A Cochrane
review published in 2013 found that PPI therapy was
superior to H2RAs and other agents for the relief of
GERD-like symptoms.10 Acid suppression should be the
target of therapy for patients with GERD unless there has
been more in-depth diagnostic testing. The recommended dosing and duration for PPI therapy
per the ACG guidelines is once daily for approximately
8 weeks.7 For patients who have a partial response after
8 weeks, the dosing frequency can be increased to twice
daily in order to achieve optimal symptom relief. Patients
who have no response after 8 weeks should be referred
to a gastroenterologist for further evaluation.7 Longterm therapy should be reserved for patients whose
symptoms return once the PPI therapy is stopped, or if
there are complications such as Barrett’s esophagus or
erosive esophagitis.7 Histamine receptor antagonists may
be considered in lieu of PPIs if there is no presence of
complications. Also, the addition of a nighttime dose of an
H2RA to the daytime regimen of a PPI may be considered
if the patient experiences nocturnal symptoms. However,
this may lead to tolerance after several weeks of therapy.7,11
Although the ACG guidelines do not specifically address
the use of antacids, these agents can be used for immediate
relief of GERD symptoms, especially if the symptoms
occur after eating.1 The ACG recommends against
the use of non-acid suppression therapy such as with
metoclopramide or baclofen (i.e. prokinetic agents) in
adults without further diagnostic evaluation.7 These agents
have not been shown to improve symptoms for patients
without underlying factors.12 Likewise, sucralfate (i.e.
surface agent) is not recommended for use in non-pregnant
patients for the management of GERD symptoms.7
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General Management
The step-up or step-down approach may be recommended
for an adult patient with GERD. There are advantages and
disadvantages to either management strategy. In the step-up
approach, antacids and H2RAs would be tried first and the
potency of therapy would increase until the patient achieved
symptom control. Therefore, PPIs could be avoided and would
save the patient medication costs along with limiting exposure
to safety issues. However, it could take a longer period of
time to achieve symptom control, if antacids and H2RAs are
ineffective. In a step-down approach, the most potent agents
- the PPIs - are initiated first, which can provide fast relief.
However, PPIs are most often the most expensive antisecretory
agents available over-the-counter or as a prescription.
Depending on the PPI, a prior authorization of previous agents
may be needed for insurance coverage. Treatment with a PPI
can be tapered down until the patient’s treatment is guided
with antacids by the presence of breakthrough symptoms.
Approximately 2 to 4 weeks is adequate time to taper a PPI;
however, the higher the dose of a PPI, then the taper period
will be longer.13 If the patient is tolerant to a lower dose, then
step-down therapy may include H2RA once-daily or as-needed
antacids. If the patient is intolerant to a lower dose of PPI,
then the previous dose should be resumed.13 Table 3 provides
a general approach and management strategies for an adult
patient with GERD.
Proton Pump Inhibitors
Proton pump inhibitors have become the preferred agents in
persistent or moderate GERD management. As mentioned
before, a recent Cochrane review found that short-term use of
PPIs were more effective than H2RAs and prokinetic agents
at reducing heartburn and GERD-related symptoms.10 Proton
pump inhibitors reduce gastric acid by inhibiting the
hydrogen-potassium adenosine triphosphatase (ATPase) in
gastric parietal cells.14 This enzyme is the last step during
the acid secretion process in the stomach. There are many
PPIs now available, both by prescription only and over-thecounter. Table 4 outlines the options available.
These agents are metabolized by the cytochrome P450 (CYP)
system in the liver. This may lead to some drug interactions,
although major interactions are rare. The most common
enzyme affected during the metabolism of PPIs is CYP2C19,
although inhibition is to varying degrees. The strongest PPI
inhibitor of CYP2C19 is omeprazole and its use should be
avoided when use of this enzyme is critical, such as with
clopidogrel, according to the manufacturer and the Food
and Drug Administration.15 Clopidogrel is a pro-drug that
is activated by CYP2C19, so its therapeutic effects may be
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lessened by concomitant administration with strong
enzyme inhibitors.16 However, the ACG contends that
there is no need to change a patient’s PPI therapy solely
due to concomitant use of clopidogrel due to the lack of
evidence in regards to clinical cardiovascular outcomes
in these patients.7
Patients should be counseled on proper administration
of PPIs. The older agents, such as omeprazole,
esomeprazole, and lansoprazole, should be taken
prior to eating in order to achieve maximal acid
suppression.17 Typically, PPIs should be taken 30-60
minutes before breakfast or at least the largest meal of
the day. The newer PPIs, including dexlansoprazole,
pantoprazole, and rabeprazole, can be administered
without regard to meals.17 However, premeal
administration is recommended if there is no relief once
taken after eating.
While PPIs are generally well tolerated, there are a few
adverse effects that should be noted when counseling
a patient. The most common adverse effects include
diarrhea, nausea or vomiting, abdominal pain, and
headache.18 Chronic or long-term use of PPIs is linked
to more serious adverse effects, including Clostridium
dificile-associated diarrhea and osteoporosis-related
fractures, while short-term use has also been linked to
an increased risk of community-acquired pneumonia.7
Chronic use may also cause hypomagnesemia,
particularly in patients who take other therapies that
are also linked to reduced magnesium levels, such as
digoxin or diuretics. Vitamin B12 deficiency has been
linked to long-term PPI use, especially in patients
who take PPIs twice daily for at least 2 years.19 Also,
rebound hypersecretion of acid is possible if PPIs are
stopped abruptly, rather than tapering down doses when
therapy is completed.
Most of the PPIs are pregnancy category B, and are
considered safe to use during pregnancy. Omeprazole
and esomeprazole are labeled as a pregnancy category
C, but are considered to have a low risk for negative
effects on the fetus.20 Proton pump inhibitors do not
require dosage adjustments in renal impairment, but
may in the presence of severe hepatic impairment. Histamine Receptor Antagonists
Histamine-2 receptor antagonists are commonly used
for treatment of GERD symptoms. These agents inhibit
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the binding of histamine at receptors on the gastric parietal
cell, thereby inhibiting gastric acid secretion.26,27 Like
PPIs, there are many options available, both by prescription
only and over-the-counter. Table 4 details the available
options. Like PPIs, H2RAs are generally well tolerated.
The most common side effects for these agents include
headache, dizziness, constipation, and diarrhea.26-30 Similar
to PPI therapy, long-term use of H2RAs has also been
linked to vitamin B12 deficiency, particularly in patients
who take these medications for at least 2 years.19
Since the H2RAs are eliminated by the kidneys, it is
important to monitor renal function during therapy. Once
the estimated creatinine clearance is reduced to less than 50
ml/min, the dose of these agents should be cut in half. In
clinical practice, this dose adjustment is typically done by
reducing the dosing frequency from twice daily to once
daily. Failure to reduce the dose in renal insufficiency may
lead to confusion in patients due to decreased clearance of
the medication. Histamine receptor antagonists are labeled
as a pregnancy category B, and may be used if clinically
indicated.26-30 Antacids
Antacids are readily available over the counter and may
be sought by patients for quick relief. Antacids such as
calcium salts are useful for mild or intermittent GERD
symptoms; these agents can also be used as adjuvant
therapy with H2RAs or PPIs. Antacids are not useful as
chronic therapy and do not heal esophagitis. These agents
neutralize gastric acidity as well as improve the lower
esophageal sphincter tone and are intended to be taken on
an as needed basis.1,6,7 There are several antacids preparations - aluminum,
calcium, and magnesium salts. Each salt has a quick onset
and short duration of action, which may require frequent
administration during the day (i.e. three to four times per
day). Antacids are well tolerated, but a patient should be
counseled on the most common adverse events. These
may vary depending on the salt. Constipation may occur
with aluminum and calcium-based formulation, whereas
a patient may experience diarrhea with a magnesiumbased formulation. In general, antacids have a chalky
taste and could cause abdominal pain. A thorough
medical history should be obtained prior to recommending
antacids as caution should be utilized among patients with
renal dysfunction because accumulation may occur. In
addition, antacids may bind to certain medications, such as
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fluoroquinolones, making the bound drugs ineffective.
A thorough review of the patient’s medication profile is
warranted when recommending antacid therapy, and the
patient may be required to separate the administration
of the interacting medication by several hours.
Other
Other options that may be considered in the
management of GERD symptoms include prokinetic
and surface agents. Metoclopramide is a prokinetic
agent with antidopaminergic properties that increases
the pressure at the LES and facilitates gastric
emptying.8 The most common adverse effects
include extrapyradimal side effects, including tardive
dyskinesia.31 Other common adverse effects include
lethargy and irritably. Other prokinetic agents that may
also be used in refractory cases include erythromycin,
bethanechol, and baclofen. Sucralfate is a surface agent that is not
routinely recommended for management in GERD,
nor is it FDA-approved. It is more commonly used
in the presence of erosive esophagitis or an ulcer, in
addition to acid suppression therapy.32,33 Sucralfate
forms a complex over the injured tissue in the stomach,
protecting it from further injury by acid. It has also
been shown to inhibit pepsin activity in gastric juices
by almost 30%.32 Constipation is the most common
adverse event associated with use.32,33 Role of the Pharmacist
It is very likely that a pharmacist will encounter
patients suffering from GERD regardless of setting,
and pharmacists may serve various roles. A
pharmacist can help assess and identify the potential
problem to recommend appropriate treatment or
refer the patient for immediate attention. Based on
the patient’s complaints and risk factors for GERD,
nonpharmacologic interventions can be reviewed and
recommended as initial and/or adjunctive treatment
for the individual. Patients who have mild symptoms
may be appropriate candidates to practice self care. The
pharmacist can discuss the general approach, design an
individualized plan from the evidence-based guidelines,
and recommend a specific agent, based on the symptom
frequency, duration, and/or severity. For patients with
more severe or prolonged symptoms, the pharmacist
should make a referral to a primary care provider. In
these scenarios, the pharmacy may suggest treatment
recommendations to the medical provider. Once a
34
specific agent is selected and recommended, the pharmacist
can screen for drug interactions, review the role of the agent
and timing of onset, and provide education on the appropriate
dosing and potential adverse events. For a pregnant woman,
it is important to evaluate and determine the most appropriate
agent based on the pregnancy category rating. The pharmacist
can help make cost-effective selections for therapy, as well as
recommend alternatives if there is a shortage. Conclusion
Gastroesophageal reflux disease is a common condition that
will be encountered by pharmacists in any practice setting
- community, ambulatory care, and hospital. This disease
requires an effective and patient-centered therapeutic plan
to achieve symptom control, prevent complications, and
improve quality of life. Guidelines have been published
for pediatric and adult patients to guide diagnosis and
therapeutic plans. These guidelines supplement clinical
judgment. Nonpharmacologic interventions should be specific
for each patient. Pharmacotherapy is effective in symptom
control based on the frequency and severity of a patient’s
clinical features. Further diagnostic tests or referral to a
gastroenterologist may be necessary in patients unable to
achieve control with specific agents or have refractory GERD.
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AHRQ Publication No. 11-EHC049-EF. Rockville, MD: Agency for
Healthcare Research and Quality. September 2011. Available at:
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
24. Prevacid (lansoprazole) delayed-release capsules and orally
disintegrating tablets [product information]. Deerfield, IL: Takeda
Pharmaceuticals Inc, September 2012.
25. Protonix (pantoprazole sodium) delayed-release tablets and oral
suspension [product information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc, May 2012.
26. Axid (nizatidine USP) capsules [product information]. Liberty
Corner, NJ: Reliant Pharmaceuticals, Inc, March 2005.
27. Axid (nizatidine USP) oral solution [product information]. Liberty Corner, NJ: Reliant Pharmaceuticals Inc, August 2004.
28. Pepcid (famotidine) tablets and oral suspension [product information]. Whitehouse Station, NJ: Merck & Co Inc, October 2006.
29. Tagamet (cimetidine) tablets [product information]. Boronia,
Victoria: GlaxoSmithKline Australia Pty Ltd, March 2008.
30. Zantac (ranitidine hydrochloride) tablets, EFFERdose tablets,
and syrup [product information]. Research Triangle Park, NC:
GlaxoSmithKline, April 2009.
31. Reglan (metoclopramide) tablets [product information]. Marietta, GA: Alaven Pharmaceutical LLC, November 2010.
32. Carafate (sucralfate) suspension [product information]. Bridgewater, NJ: Aptalis Pharma US Inc, March 2013.
33. Carafate (sucralfate) tablets [product information]. Mont St
Hilaire, Quebec: Aptalis Pharma Canada Inc, September 2013.
19. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump
inhibitor and histamine 2 receptor antagonist use and vitamin B12
deficiency. JAMA 2013;310(22):2435-42.
20. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy
and lactation, 9th edition [medical app] DxPregLac9; version
14.0.5/2012.02.06 May 2013 Lippincott Williams & Wilkins; 2011.
Palmetto Pharmacist • Volume 55, Number 4
35
JOURNAL CE
Table 1. Exacerbating Factors
Pathophysiologic Changes Decreased saliva
Slowed gastric emptying
Impaired esophageal
peristalsis
Medical Conditions
Zollinger-Ellison Syndrome
Obesity
Pregnancy
Gastroparesis
Hiatal hernia
Medications
Anticholinergic agents
Progesterone
Beta-adrenergic antagonists
Calcium channel blockers
Nitrates
Dietary Substances
Fatty foods
Chocolate
Peppermint
Ethanol
Acidic foods
Spicy foods
Adapted from: Kahrilas PJ. Diagnosis of symptomatic
gastroesophageal reflux disease. Am J Gastroenterol 2003;98:S1523.
Box 1. Definitions of Symptoms Related to Gastroesophageal Reflux Disease
Heartburn is a common symptom that occurs after a meal and is generally a burning sensation in the
retrosternal area.
• Regurgitation is a mixture of acidic material and undigested food. It is described as the back flow of
gastric contents into the mouth and/or pharynx.
• Dysphagia is difficulty with swallowing and occurs from longstanding or recurring heartburn.
Adapted from: Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a
global evidence-based consensus. Am J Gastroenterol 2006;101:1900-20.
36
Palmetto Pharmacist • Volume 55 Number 4
JOURNAL CE
Table 2. List of Diagnostic Tests for Gastroesophageal Reflux Disease
Diagnostic Test
Purpose
When It should be Used
Endoscopy
• Observation of epithe• Any patient older than 45 years
lium lining and identifica- • Patients with alarming symptoms
tion of Barrett’s esopha- • Patients with refractory GERD
gus and complications of
GERD
Manometry
• Evaluation of peristaltic
• Patients with a suspected a motility problem with
function of the esophaesophagus
gus in patients with normal endoscopic findings
prior to pH testing
pH Testing
• Determination of percent • Patients with mucosal changes on endoscopy
time pH is less than 4 in • Patients with normal manometry who have symptoms
a 24-hour period
• Patients with refractory GERD
• Patients with continued symptoms despite therapy
• Evaluation of postprandi- • Pediatric patients with suspected GERD
al reflux and assessment
of gastric emptying
Adapted from: Kahrilas PJ, Shaheen NJ, Vaezi MF. American Gastroenterologic Association Medical Position Statement on the
Management of Gastroesphageal Reflux Disease. Gastroenterology 2008;135:1383-1391; Katz PO, Gerson LB, and Vela MF. Diagnosis
and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-28.
Table 3. General Pharmacologic Management of Gastroesophageal Reflux Disease
Adults
Classification
Initial Therapy
Other Options
Comments
Mild and/or
- Antacids as needed
- Low-dose H2RA as needed
- Doses can be adjusted
every 2 to 4 weeks.
intermittent
- Standard-dose H2RA twice
- If symptom control is
symptoms
daily
not achieved, then con- High-dose H2RA
sider PPIs for at least 8
weeks.
- Different H2RA
Severe and/
or frequent
symptoms
- Standard-dose PPI
once daily
- Low-dose PPI
- Standard-dose or low-dose
H2RA
- Antacids, as needed
Palmetto Pharmacist • Volume 55, Number 4
- If symptom control is
achieved after 8 weeks,
then treatment can be
decreased.
- If symptoms control is
not achieved after 8
weeks, then consider
additional options for
refractory GERD.
37
JOURNAL CE
Refractory
- Standard-dose PPI
- Different PPI
- Twice-daily PPI can be
administered prior to
symptoms
twice daily
- Antireflux surgery
the morning and evening meals.
- A standard-dose H2RA
at bedtime could be
given with twice-daily
PPI.
- Metoclopramide is not
recommended for this
classification.
- Abbreviations: H2RA = histamine-2 receptor antagonist; PPI = proton pump inhibitor
Adapted from: Lightdale JR, Gremse DA, and Section on Gastroenterology, Hepatology, and Nutrition. Gastroesophageal reflux:
Management guides for the pediatrician. Pediatrics 2013;131:1684-95; Kahrilas PJ, Shaheen NJ, Vaezi MF. American Gastroenterologic
Association Medical Position Statement on the Management of Gastroesphageal Reflux Disease. Gastroenterology 2008;135:1383-1391;
Katz PO, Gerson LB, and Vela MF. Diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-28.
Table 4. Available Treatment Options for Gastroesophageal Reflux Disease
Drug
Dose (Adults)
Dosage Forms
Comment
Dexlansoprazole
available
Proton Pump Inhibitors
NERD: 30 mg once daily Delayed- release
(Dexilant)
EE: 60 mg once daily
• Approved for use
20-40 mg once daily
(Nexium)
Lansoprazole
(Prevacid)
38
15-30 mg once daily
Atazanavir
capsules (30, 60
up to 4 weeks for
Methotrexate
mg)
NERD
Tacrolimus
• No generic availEsomeprazole
Drug Interactions
Warfarin
Delayed-release
able
Available OTC: 20 mg
Atazanavir
capsules (20, 40
Infant dose approved for
Cilostazol
mg) and oral pow- up to 6 weeks; all other
Clopidogrel
der for suspension approved up to 8 weeks
Methotrexate
(2.5, 5, 10, 20,
Nelfinavir
and 40 mg)
Saquinavir
Delayed-release
Tacrolimus
Atazanavir
Available OTC: 15 mg
capsules and
Methotrexate
orally disintegrat-
Tacrolimus
ing tablets (15 mg,
Theophylline
30 mg)
Warfarin
Palmetto Pharmacist • Volume 55 Number 4
JOURNAL CE
Omeprazole
20 mg once daily
(Prilosec)
Delayed-release
Available OTC: 20 mg
Atazanavir
capsules (10, 20,
and in combination with
Cilostazol
40 mg) and oral
sodium bicarbonate (Ze-
Clopidogrel
suspension (2.5,
gerid OTC)
Methotrexate
10 mg)
Nelfinavir
Saquinavir
Pantoprazole
40 mg once daily
(Protonix)
Rabeprazole
20 mg once daily
(Aciphex)
Delayed-release
Approved for erosive
Tacrolimus
Atazanavir,
tablets (20, 40
esophagitis associ-
Nelfinavir
mg) and oral pow- ated with GERD (up to 8
Methotrexate
der for suspension weeks)
Warfarin
(40 mg)
Delayed-release
Atazanavir
No generic available
tablets (20 mg)
Cyclosporine
and capsules (5,
Methotrexate
Cimetidine (Ta-
10 mg)
Histamine-2 Receptor Antagonists
800 mg per day in one
Tablets (200, 400 Available OTC
Numerous; inhib-
gamet)
or up to 4 divided doses
its CYP1A2, 2C9,
mg)
Warfarin
2C18, 2D6, 3A3,
Famotidine (Pep- NERD: 20 mg twice
Tablets (20, 40
3A4
Available OTC alone and None
cid)
daily
mg)
with antacids
EE: 20-40 mg twice
Oral suspension
daily
150 mg twice daily
(40 mg/5 ml)
Pulvules (150, 300 Available OTC: 75 mg;
Nizatidine (Axid)
(pulvules)
mg)
solution only approved
(solution)
Oral solution (15
for pediatrics > 12 years
Ranitidine
mg/ml)
Tablets (150, 300
old
Available OTC
(Zantac)
150 mg twice daily
None
Atazanavir
mg)
Glipizide
Effervescent tab-
Ketoconazole
lets (25 mg)
Triazolam
Syrup (15 mg/ml)
Warfarin
Palmetto Pharmacist • Volume 55, Number 4
39
JOURNAL CE
Aluminum Hy-
Varies by product
droxide
Chewable tablets,
Doses three to four times Varies by the
suspension, etc
per day
product, but chela-
Take 1 to 3 hours after
tion or increases /
meals and other medica-
decreased absorp-
tions
tion may occur
Calcium Carbonate
Magnesium Hydroxide
Sodium Bicarbonate
Metoclopramide
(Reglan)
10-15 mg up to four
Other Options
Tablets (5, 10 mg) Not approved for use in
times daily before meals Dispersible tablet
and at bedtime
children
(5 mg)
Anticholinergic
agents
CNS depressants
Solution (1 mg/ml,
Sucralfate (Carafate)
1 gm four times daily
5 mg/ml)
Tablet (1 gm)
•Generic not avail- Cimetidine
Suspension (1
able for suspen-
Fluoroquinolones
gm/ml)
sion
Digoxin
•Not approved for
use in children
Levothyroxine
Phenytoin
Ranitidine
Theophylline
Tetracycline
Abbreviations: CNS = central nervous system; CYP = cytochrome; EE = erosive esophagitis; GERD = gastroesophageal reflux disease;
gm = gram; mg = milligram; ml = milliliter; NERD = nonerosive reflux disease; OTC = over the counter
Adapted from: Aciphex (rabeprazole sodium) delayed-release tablets and capsules [product information]. Woodcliff Lake, NJ: Eisai
Inc, November 2013; Axid (nizatidine USP) capsules [product information]. Liberty Corner, NJ: Reliant Pharmaceuticals, Inc, March
2005; Axid (nizatidine USP) oral solution [product information]. Liberty Corner, NJ: Reliant Pharmaceuticals Inc, August 2004; Carafate
(sucralfate) suspension [product information]. Bridgewater, NJ: Aptalis Pharma US Inc, March 2013; Carafate (sucralfate) tablets [product
information]. Mont St Hilaire, Quebec: Aptalis Pharma Canada Inc, September 2013; Dexilant (dexlansoprazole) delayed-release capsules
[product information]. Deerfield, IL: Takeda Pharmaceuticals America Inc, August 2013; Nexium (esomeprazole magnesium) delayedrelease capsules and oral suspension [product information]. Wilmington, DE: AstraZeneca LP, March 2014; Pepcid (famotidine) tablets
and oral suspension [product information]. Whitehouse Station, NJ: Merck & Co Inc, October 2006; Prevacid (lansoprazole) delayedrelease capsules and orally disintegrating tablets [product information]. Deerfield, IL: Takeda Pharmaceuticals Inc, September 2012;
Prilosec (omeprazole and omeprazole magnesium) delayed-release capsules and oral suspension [product information]. Wilmington,
DE: AstraZeneca LP, March 2014; Protonix (pantoprazole sodium) delayed-release tablets and oral suspension [product information].
Philadelphia, PA: Wyeth Pharmaceuticals Inc, May 2012; Reglan (metoclopramide) tablets [product information]. Marietta, GA: Alaven
Pharmaceutical LLC, November 2010; Tagamet (cimetidine) tablets [product information]. Boronia, Victoria: GlaxoSmithKline Australia Pty
Ltd, March 2008; Zantac (ranitidine hydrochloride) tablets, EFFERdose tablets, and syrup [product information]. Research Triangle Park,
NC: GlaxoSmithKline, April 2009.
40
Palmetto Pharmacist • Volume 55 Number 4
JOURNAL CE
Management of Uncomplicated GERD in Adult Patients
Corresponding Course Program Number: 0171-9999-15-037-H01-P
1. Complete and mail entire page. SCPhA members can take journal CE for free; $15 for non-members. Check must
accompany test. You may also complete the test and submit payment online at www.scrx.org.
2. Mail to: Palmetto Pharmacist CE, 1350 Browning Road, Columbia, SC 29210-6309.
3. Continuing Education credits will be uploaded to the CPE Monitor System within six weeks from the submission date
for the quiz once the evaluation form and payment are received. Notification will be sent via email if you have not successfully completed the quiz.
4. Participants scoring 70% or greater and completing the program evaluation form will be issued CE credit.
Participants recieving a failing grade on any examination will have the examination returned. The participant
will be permitted to retake the examination one time at no extra charge.
South Carolina Pharmacy Association is accredited by the Accreditation Council for Pharmacy Education as providers for continuing education. This article is approved for 1 contact hour of contiuning education credit (ACPE: UAN:
0171-9999-15-037-H01-P). This CE credit begins 06/15/2015 and expires 06/15/2018.
Name _______________________________ License # _________________ Birth Month/Day (MM/DD)___________
Address _________________________________________________________________________________________
NABP eID ______________ Phone _______________ Email ______________________________________________
EVALUATION (circle the appropriate response)
1. Did the article achieve the stated objects?
(Note at all) 1
2
3
4
5 (Completely)
2. Overall evaluation of the article?
3. Was the information relevent to your practice?
(Poor) 1
2
3
4
5 (Excellent)
(No) 1
2
3
4
5 (Yes)
4. How long did it take you to read the article and complete the exam? _______________
CE credit will ONLY be awarded when a submitted test is accompanied by completing the evaluation above or online at www.scrx.org.
Self-assessment questions
1. According to the Montreal definition, gastroesophageal reflux disease (GERD) develops when symptoms are:
a.
Mild
b.
Infrequent
c.
Persistent
d.
Troublesome
LO#1 (Answer can be found in the Introduction section.)
2. Increased abdominal pressure that leads to inappropriate relaxation of the lower esophageal sphincter (LES) may be
present in patients who are _______________________.
a.
Underweight
b.
Not pregnant
c.
Obese
d.
Normal weight
LO#1 (Answer can be found in the Introduction section.)
3. While many people may consume or use this after eating, it may actually exacerbate GERD symptoms.
a.
Peppermint
b.
Water
c.
Chewing gum
d.
Skim milk
LO#1 (Answer can be found in Table 1 in which exacerbating factors are listed.)
Palmetto Pharmacist • Volume 55, Number 4
41
JOURNAL CE
4. Surgery is not a consideration for long-term management of GERD symptoms for patients who have:
a.
Complete response to famotidine
b.
Complete response to lansoprazole
c.
No response to esomeprazole
d.
Partial response to ranitidine
5. Which one of the following is a classic symptom of GERD for an adult patient?
a.
Odynophagia
b.
Hoarseness
c.
Regurgitation
d.
Weight loss
LO#1 (Answer can be found in Clinical presentation for an adult patient.)
6. Recommendations for lifestyle modifications to control GERD symptoms may include:
a.
Routine avoidance of certain foods
b.
Eating meals within 2-3 hours of bedtime
c.
Lowering the head of the bed
d.
Weight loss if overweight or obese
LO#3 (Answer can be found under Nonpharmacologic interventions for an adult patient.)
7. Which of the following proton pump inhibitors may be taken without regards to meals?
a.
Dexlansoprazole
b.
Esomeprazole
c.
Lansoprazole
d.
Omeprazole
LO #3 (Answer can be found within the subsection Proton pump inhibitors under the General management section.)
8. Short-term use of proton pump inhibitors has been linked with an increased risk of:
a.
Clostridium difficile-associated diarrhea
b.
Community acquired pneumonia
c.
Hypomagnesemia
d.
Osteoporosis-related fractures
LO #3 (Answer can be found within the subsection Proton pump inhibitors under the General management section.)
9. A 29-year-old gentleman complains of classic GERD symptoms intermittently in the evening. He wants a product with the
quickest “relief”. Which one of the following agents is the best choice for this patient?
a.
Calcium carbonate
b.
Cimetidine
c.
Dexlansoprazole
d.
Metoclopramide
LO#3 (Answer can be found in the subsection Antacids under General Management.)
10. A patient presents to his local community pharmacist and complains of classic GERD symptoms. Which one of the
following questions would be the most important question that a pharmacist can ask?
a.
Do you eat chocolate or drink alcohol often?
b.
How often are these symptoms occurring?
c.
Have you called or seen your doctor lately?
d.
Are you taking a proton pump inhibitor?
LO#4 (Answer can be found two sections related to GERD among an adult patient (i.e. Clinical presentation; Role of
pharmacist)
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