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PACT Centre
Pages - DRUGS FOR DYSPEPSIA
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| Dyspepsia
is any symptom of the upper gastrointestinal (GI) tract,
present for 4 weeks or more, including upper abdominal
pain or discomfort, heartburn, acid reflux, nausea, or
vomiting.1 Each year about 40% of adults suffer from dyspepsia,
5% will consult their GP and 1% are referred for endoscopy.1
Of those patients who have dyspepsia investigated by endoscopy,
40% have gastro-oesophageal reflux disease (GORD), 40%
non-ulcer dyspepsia and 13% some form of ulcer. Over the
last 5 years prescribing of proton pump inhibitors (PPIs)
has increased whilst prescribing of antacids and H2-receptor
antagonists (H2RAs) has fallen (Chart 1). Spending on
drugs to treat dyspepsia has decreased from a peak in
December 2004 (Chart 2); this is mainly due to price reductions
for the H2RAs, omeprazole and lansoprazole. |
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| Trends in Prescribing of Drugs for Dyspepsia in General Practice in England (Chart 1) |
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| Trends
in Spending on Antacids and Ulcer Healing Drugs in England
(Chart 2) |
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All
patients should be referred for endoscopic investigation
urgently (within 2 weeks) where any of the following
alarm symptoms are present: chronic GI bleeding, progressive
unintentional weight loss, progressive difficulty swallowing,
persistent vomiting, iron deficiency anaemia, epigastric
mass or suspicious barium meal.1 Patients aged 55 years
and older with unexplained and persistent recent-onset
dyspepsia alone should also be referred urgently for
endoscopy.1 Unexplained dyspepsia is defined as symptom(s)
and/or sign(s) that have not led to a diagnosis being
made by the primary care professional after initial
assessment of the history, examination and primary care
investigations. Less than 3% of patients who have an
endoscopy will have gastric or oesophageal cancer.1
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Uninvestigated
dyspepsia
Lifestyle
advice (including healthy eating, weight reduction,
smoking cessation and alcohol intake) and medication
review should be offered to all patients with dyspepsia.
Self-treatment with antacid and/or alginate therapy
is suitable for most patients, however additional therapy
may be required where symptoms do not respond or worsen.
Treatment of uninvestigated dyspepsia is either to test
for and eradicate Helicobacter pylori or to use empirical
treatment with a PPI for one month.1 In trials of patients
with uninvestigated dyspepsia PPIs are more effective
at reducing symptoms of dyspepsia than antacids and
H2RAs (numbers needed to treat (NNT) 6 and 5 respectively).1
A H2RA or prokinetic drug may benefit individual patients
if a PPI provides an inadequate response. It may be
appropriate to refer the minority of patients who do
not respond to therapy to a specialist.1
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Helicobacter
pylori: testing and eradication
H. pylori is present in approximately 40% of the UK
population and probably causes no harm in most people.1,2
Before testing for H. pylori it is necessary to withdraw
PPIs for 2 weeks. A non-invasive carbon urea breath
test or stool antigen test is usually used to test for
H. pylori; both tests show better specificity than serology
testing. Eradication treatment should be prescribed
for H. pylori positive patients consisting of a 7-day
course of a PPI, with either metronidazole 400mg and
clarithromycin 250mg, or amoxicillin 1g and clarithromycin
500mg.1 Any re-testing for H. pylori should be performed
using a carbon urea breath test.
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Gastro-oesophageal
reflux disease (GORD)
Previously GORD would be diagnosed when reflux symptoms
were predominant,2 however, patients with uninvestigated
'reflux-like' symptoms should be managed as patients
with uninvestigated dyspepsia.1 GORD refers to oesophagitis
determined by endoscopic examination or endoscopy-negative
reflux disease (i.e. no oesophageal mucosal breaks seen
on endoscopy). A treatment dose of a PPI for 1 or 2
months should be offered to patients with GORD.1 For
recurring symptoms after initial treatment, a PPI should
be offered with a limited number of repeat prescriptions,
and at the lowest dose possible to control symptoms,
patient care should be reviewed at least annually.1
PPIs reduce relapse in people with healed reflux oesophagitis
compared with H2RAs and placebo.3 There are no long-term
trial data for PPI therapy in endoscopy-negative reflux
disease. However, rather than patients taking continuous
therapy it seems cost-effective to offer patients either
intermittent one month full dose therapy or as-required
PPI treatment.1 H. pylori eradication does not benefit
people with GORD.4 For the small number of patients
who have persistent symptoms despite PPI treatment,
the options include double dose PPI therapy, adding
a H2RA at bedtime and extending the treatment length.1
Barrett's oesophagus affects a small minority of people
with GORD; it is diagnosed in 1.4% of endoscopies in
the UK.1 Barrett's oesophagus increases the risk of
adenocarcinoma, however the size of this increased risk
has not been quantified. There is insufficient evidence
to assess the clinical effectiveness of continued endoscopic
surveillance for Barrett's oesophagus.5
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Non-ulcer
dyspepsia (NUD)
If H pylori are present in patients with NUD,
this should be eradicated and symptoms will improve in
around 36% of patients, however over a 3-12 month period
around 57% of substantial symptoms will remain.1 If patients'
symptoms persist following treatment or exclusion of
H. pylori, a low dose PPI or H2RA should be offered
for one month and then continued on an as-required basis
with a limited number of repeat prescriptions.1 Antacid
therapy is not effective for reducing symptoms of NUD.1 |
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Peptic ulcer disease (PUD)
Up to 95% and 70% of patients with proven duodenal ulcers and gastric ulcers, respectively, will have H. pylori infection.6 Patients who are H. pylori positive should be offered eradication therapy which increases duodenal ulcer healing (NNT 18) and reduces recurrence (NNT 2) compared to patients receiving acid suppression therapy only.1 Gastric ulcer healing rates are not increased with H. pylori eradication compared to acid suppression alone, however, recurrence of gastric ulcer is improved. Patients with gastric ulcer and H. pylori should receive a repeat endoscopy and retesting for H. pylori at 6-8 weeks after beginning treatment.1 Non-steroidal anti-inflammatory drug (NSAID) use should be stopped where possible in patients diagnosed with PUD. A PPI or H2RA for 2 months should be given to patients with NSAID-induced PUD, and if H. pylori is present eradication therapy should be offered subsequently.1 H. pylori negative patients who do not take NSAIDs should receive treatment doses of a PPI or a H2RA for 1-2 months, which heals peptic ulcers in most cases. |
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Gastroprotection
with NSAIDs
Before prescribing an NSAID, patients should be assessed
for the risk of GI adverse effects and NSAIDs should be
avoided in patients at high risk (risk factors include:
age over 65 years; using other medicines known to increase
the chance of upper GI adverse events; serious co-morbidity
and previous history of PUD/dyspepsia). Patients who need
an NSAID but are at high risk of GI adverse events could
take a gastroprotective agent with their NSAID; PPIs are
most often prescribed. Alternatively misoprostol could
be tried since it reduces the risk of clinically important
ulcer complications.7 For patients who experience dyspepsia
while taking low dose aspirin, a PPI should be tried before
prescribing clopidogrel instead of aspirin.8 Clopidogrel
can be considered where aspirin is contraindicated or
there is genuine aspirin intolerance. NSAIDs and Cox-II
selective inhibitors increase the risk of hypertension,
heart failure and renal failure. Cox-II selective inhibitors
are associated with a moderate increase in the risk of
vascular events, in particular myocardial infarction.9,10
The balance of GI and cardiovascular risk should be considered
in all patients before prescribing a Cox-II selective
inhibitor.9 There is no good evidence to support the use
of Cox-II selective inhibitors instead of traditional
NSAIDs to reduce serious upper GI complications and NSAID-associated
dyspepsia.11 There is still a high volume of prescription
items for Cox-II selective inhibitors despite a sharp
decline over the last 2 years (649,000 items quarter to
March 2006). Prescribing of NSAIDs (including Cox-II selective
inhibitors) fell by 12% over the last 2 years to 4.5 million
items (quarter to March 2006). |
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Variation
Between Strategic Health Authorities in Spending on
Drugs for Dyspepsia
(Quarter to March 2006) (Chart 3)
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Prices
based on Drug Tariff July 2006 or Chemist & Druggist
July 2006
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Prescribing
data
Prescribing
of PPIs has nearly doubled over the last 5 years. In the
quarter to March 2006, PPIs account for 73% of items (6.1
million) and 92% of cost (£104.5 million) for all drugs
used for dyspepsia. Lansoprazole and omeprazole are the
most commonly prescribed PPIs (2.5 million items each,
quarter to March 2006). Over the last 5 years prescribing
has risen by 78% for lansoprazole and by 109% for omeprazole.
These two drugs cost £43 million and £37 million respectively,
quarter to March 2006. Esomeprazole items have increased
to nearly 400,000 per quarter (£10.2 million). Rabeprazole
and pantoprazole account for 352,000 items and 277,000
items respectively, costing £7.4 million and £5.6 million
per quarter. Spending (NIC/1000 STAR-PUs) varies 2-fold
across strategic health authorities (SHAs) for PPIs (Chart
3). In 7 SHAs "other proton pump inhibitors" (esomeprazole,
pantoprazole and rabeprazole) account for more than 25%
of the total spend. Esomeprazole, pantoprazole and rabeprazole
offer no clinical advantage over either omeprazole or
lansoprazole, which are both cost-effective choices.2
The cost of 28 days of omeprazole or lansoprazole at treatment
doses is between a third and a half of the cost of the
newer PPI drugs (Price Chart). Prescriptions for omeprazole
and lansoprazole should be for the standard capsules or
tablets.
Prescribing of H2RAs has fallen by 33% during
the last 5 years, with cost decreasing by 74%. Ranitidine
is the most commonly prescribed accounting for nearly
82% of H2RA items (800,000) and 72% of cost (£2.5 million),
quarter to March 2006. Cimetidine accounts for 12% of
H2RA items (118,000) and 11% of cost (£0.4 million).
Items for 'drugs for dyspepsia and GORD' (BNF section
1.1) have decreased by 24% over the last 5 years to
1.3 million items, costing just under £6 million, quarter
to March 2006. Compound alginates account for 91% of
items (1.2 million) and 94% of cost (£5.6 million) for
this group of drugs. Gaviscon® is the most commonly
prescribed compound alginate, over the last 5 years
its prescribing has fallen by 31% to 888,000 items per
quarter (costing £4.9 million). Prescribing of Peptac®
has almost trebled over the last 5 years (235,000 items,
£0.5 million per quarter). There are 119,000 items for
antacids and simeticone per quarter, costing £0.38 million.
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REFERENCES
1.
National Institute for Clinical Excellence. Dyspepsia.
Management of dyspepsia in adults in primary care. Clinical
Guideline 17. August 2004 (Updated June 2005) www.nice.org.uk/page.aspx?o=CG017fullguideline
2.
National Prescribing Centre. The initial management
of dyspepsia in primary care. MeReC Bulletin 2006; 16:
9-12 www.npc.co.uk/MeReC_Bulletins/2006Volumes/Vol16_No3.pdf
3. Clinical Evidence freelance writers. Gastro-oesophageal
reflux disease. Clinical Evidence 2005;13:1-17 www.clinicalevidence.com/ceweb/conditionpdf/0403.pdf
4.
Harvey RF, Athene Lane J, Murray LJ, Harvey IM, Donovan
JL, Nair P. Randomised controlled trial of effects of
Helicobacter pylori infection and its eradication on
heartburn and gastro-oesophageal reflux: Bristol helicobacter
project. BMJ 2004; 328: 1417-1419
5. Garside R, Pitt M, Somerville M, Stein K, Price A,
Gilbert N. Surveillance of Barrett's oesophagus: exploring
the uncertainty through systematic review, expert workshop
and economic modeling. Health Technology Assessment
2006; Vol. 10: No.8 www.ncchta.org/fullmono/mon1008.pdf
6. Anonymous. H. pylori eradication in NSAID-associated
ulcers. DTB 43; 5: 37-40 http://nhsia-lin-01.niss.ac.uk/idtb/content/db/pdf0505
7. Clinical Evidence freelance writers. Non-steroidal
anti-inflammatory drugs. Clinical Evidence 2006;15:1-2
www.clinicalevidence.com/ceweb/conditionpdf/1108.pdf
8. National Prescribing Centre. Prescribing antiplatelet
drugs in primary care. MeReC Bulletin 2005; 15: 21-24
www.npc.co.uk/MeReC_Bulletins/2004Volumes/Vol15no6.pdf
9. Medicines and Healthcare products Regulatory Agency.
Cardiovascular safety of NSAIDs and selective COX-2
inhibitors. May 2006
www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2023859&ssTargetNodeId=368
10. Kearney PM, Baignet C, Godwin J, Halls H, Emberson
JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors
and traditional non-steroidal anti-inflammatory drugs
increase the risk of atherothrombosis? Meta-analysis
of randomised trials. BMJ 2006; 332: 1302-1308
11.
National Prescribing Centre. Cardiovascular risks of
COX-2 inhibitors and NSAIDs confirmed. MeReC Rapid Review
2006; 2: 1-3 www.npc.co.uk/MeReC_rapid_reviews/2006-7/rapid_review2_cox2.pdf
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SUMMARY
- Urgent
referral for endoscopic examination is indicated in
all patients with alarm symptoms and those aged 55
years and older with unexplained and persistent recent-onset
dyspepsia alone.
- A
PPI at a treatment dose should be offered to patients
with GORD for 1-2 months. If symptoms recur after
initial treatment, a PPI should be offered at the
lowest dose possible to control symptoms.
- A
low dose PPI or H2RA should be tried for one month
if symptoms persist in patients with non-ulcer dyspepsia
following testing for H. pylori and eradication if
positive.
- Patients
with peptic ulcer disease should be tested for H.
pylori and should receive eradication treatment if
positive
- If
patients require NSAIDs to manage their pain the risk
of GI adverse events should be assessed. If the patient
is high risk then a gastroprotective agent (either
a PPI or misoprostol) should be prescribed
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Quarter
to June 06
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National
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ITEMS/1000
PUs
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NIC/1000
PUs
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Antacids
and simeticone
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1.58
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£5.23
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| Compound
alginates, etc |
16.13
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£76.62
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| H2-receptor
antagonists |
13.36
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£55.47
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| Proton
pump inhibitors |
89.64
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£1,199.44
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| Prescribing
and Spending on Drugs for Dyspepsia in England for
Quarter to June 2006 |
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