Download Esomeprazole - Medicines Management in the East Lancashire

East Lancashire Medicines Management Board representing East Lancashire Hospitals NHS Trust, NHS Blackburn
with Darwen, NHS East Lancashire
East Lancashire Medicines Management Board
New Drug Recommendation
Esomeprazole (Nexium®, AstraZeneca)
Date of Issue: January 2010
Review Date: January 2012
BNF Therapeutic Class: 1.3.5 Proton Pump Inhibitors
Licensed Indications: Duodenal ulcer associated with H.Pylori, NSAID-associated gastric ulcer,
Gastro-oesphageal reflux disease
Dosage and Administration: Gastro-oesophageal reflux disease – 40mg od for 4 weeks, continued
for a further 4 weeks if not fully healed or symptoms persist, maintenance 20mg od; symptomatic
treatment in the absence of oesophagitis, 20mg od for up to 4 weeks, then 20mg od when required.
Recommendation – AMBER traffic light
• Esomeprazole should only be initiated by a consultant gastroenterologist in patients with
treatment resistant severe GORD confirmed by endoscopy, who have failed to respond to
the use of high doses of generic omeprazole and/or generic lansoprazole.
• NICE does not support the use of any PPI over another for the treatment of GORD and
esomeprazole is considerably more expensive than other PPIs.
• Esomeprazole should not be initiated by prescribers within primary care, nor should it be
used in the treatment of dyspepsia or in H.pylori eradication regimes or for any other
indication.
• After 8 weeks therapy with patients taking esomeprazole should be reviewed and stepped
down to a generic PPI where possible.
Summary
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The NICE clinical guideline on the primary care management of dyspepsia and GORD and other
associated conditions, discusses the use of all PPIs including esomeprazole. There is a need to
ensure that local use of PPIs is in line with national guidance.
Esomeprazole is not licensed for use in dyspepsia.
Esomeprazole is not recommended in East Lancs as part of the H.pylori eradication regime, nor for
treatment or prophylaxis of NSAID-associated ulcers. Drugs of choice in East Lancs are omeprazole or
lansoprazole for these indications.
Interventions recommended by NICE for gastro-oesophageal reflux disease (GORD) include offering
patients who have GORD a full-dose PPI for 1 or 2 months. Then if symptoms recur following initial
treatment, offer a PPI at the lowest dose possible to control symptoms, with a limited number of repeat
prescriptions.
In endoscopically-proven oesophagitis unresponsive to PPI, an extra four weeks of PPI therapy may be
beneficial. In severe (LA grade C or D) oesophagitis the dose of PPI may need to be increased or
esomeprazole may be initiated. In nocturnal symptoms unresponsive to PPI therapy it may be worth
trying an additional histamine2 receptor blocker (H2RA) at bedtime, although the efficacy of this
strategy may diminish over time.
NICE does not advocate the use of one PPI in preference to another. Previous systematic reviews
suggest that there is no statistically significant difference between the different PPIs at equivalent
doses. As such, the first line choices of PPIs in East Lancashire are generic omeprazole or
lansoprazole, which are significantly less expensive and just as effective at equivalent doses.
Esomeprazole should therefore not be initiated in patients with GORD as a first line therapy.
Omeprazole first line, and then lansoprazole second line should be used in all treatment resistant cases
before consideration is given to using esomeprazole. There is however insufficient evidence that at
equivalent doses esomeprazole is any more effective than other PPIs. Treatment with esomeprazole
should only be initiated by a consultant gastroenterologist in line with these guidelines.
Guidance above to be read in conjunction with the manufacturer’s SPC.
For NHS use only – Not to be used or reproduced for commercial purposes
Red light = only to be prescribed within secondary care, specialist initiation only: GPs should not be asked to prescribe
Amber light = only to be initiated in secondary care with follow up prescribing by primary care without a shared care agreement
Amber light with Shared Care = only to be initiated in secondary care with follow up prescribing by primary care with a shared care agreement
Green light = prescribing is appropriate in both primary and secondary care within the specified conditions
Black list = Not included in the East Lancs Joint Formulary. Not recommended for prescribing in primary or secondary care. This may be
due to lack of good clinical evidence or more suitable alternatives available.
Background
Esomeprazole, the s-isomer of omeprazole was approved for use at Burnley General Hospital in May
2003, for gastroenterologist use only in the treatment of endoscopically-proven GORD of LA grade C
or D severity. Esomeprazole was never approved for use within the Blackburn Hospitals.
Esomeprazole is not licensed for use in dyspepsia, nor is it included in the locally-recommended
H.pylori eradication scheme. Consequently esomeprazole in the treatment of GORD is the only
indication discussed below:
Generic omeprazole and lansoprazole are considered the PPIs of choice within East Lancashire.
Currently omeprazole and lansoprazole are both considerably cheaper than other PPIs on an
equivalent dose basis across both primary and secondary care. They are also both licensed for a
wider range of indications than other PPIs, including Zollinger Ellison syndrome (a hypersecretory
disorder).
Prescribing data indicate that esomeprazole use across the three PCTs is high, suggesting a number
of patients are being initiated on esomeprazole within primary care.
The publication of the NICE clinical guideline on the management of dyspepsia in primary care in
August 2004 has prompted a review of the use of esomeprazole to ensure local recommendations
are in line with national guidance1. NICE clinical guideline does not cover treatment within the
hospital setting, although sources of trial evidence are from both primary and secondary care
settings.
Within East Lancashire a Joint Medicines Formulary is intended to guide drug choice and ensure
continuity of treatment across primary and secondary care. An East Lancs decision on the place of
esomeprazole should be applicable to both Blackburn and Burnley hospitals and primary care.
Clinical Evidence – NICE Recommendations1.
Interventions for gastro-oesophageal reflux disease (GORD)
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Offer patients who have GORD a full-dose PPI for 1 or 2 months.
•
If symptoms recur following initial treatment, offer a PPI at the lowest dose possible to control
symptoms, with a limited number of repeat prescriptions.
Patients with GORD not responding to initial therapy
The symptoms of the majority of patients with GORD are improved by PPI therapy. A minority of
patients have persistent symptoms despite PPI therapy and this group remain a challenge to treat.
Therapeutic options include doubling the dose of PPI therapy, adding an H2 receptor antagonist at
bedtime or extending the duration of treatment. Most of the following evidence relates to patients
with endoscopically-proven oesophagitis.
-Increasing the duration of therapy
Data suggest that there may be additional benefit in increasing the duration of therapy from 4 to 8
weeks if patients do not initially respond to PPIs.
-Doubling the dose of PPIs
Doubling the dose of PPI may have a small effect in healing oesophagitis at 4 weeks.
Two studies evaluating healing rates according to severity of oesophagitis, suggested that by using a
double dose of a PPI this would result in an absolute increase of 10-20% in healing rates in LA grade
C and D patients. This was a post-hoc subgroup analysis and results should be treated with caution.
Nevertheless, it may be appropriate to increase the dose of the PPI if LA grade C and D patients fail
to respond to full doses of PPI. Severe oesophagitis represents only approximately 5% of all GORD
and it is therefore not appropriate to increase the dose of PPI beyond full licensed doses used for the
treatment of GORD unless there is endoscopic evidence of LA grade C or D oesophagitis.
-Use of an H2RA
In nocturnal symptoms unresponsive to PPI therapy it may be worth trying an additional H2RA at
bedtime although the efficacy of this strategy may diminish over time.
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Choice of PPI
Agreement was previously reached at Burnley General Hospital agreement to use esomeprazole in
resistant grade C or D GORD, based on a study which showed a statistically higher response rate for
esomeprazole 40mg vs. omeprazole 20mg (non-comparative doses).
However, a recent meta analysis investigated whether there is there any real difference between
PPIs for the treatment of GORD.2 The meta-analysis identified all double-blinded randomized
controlled trials comparing one PPI with another for the treatment of GORD, using endoscopicallyproven healing as the reference standard for treatment success. A total of 19 studies with more than
9,000 patients were identified, most lasting 4 weeks. The following comparisons were studied:
pantoprazole 40 mg vs omeprazole 20 mg; pantoprazole 20 mg vs omeprazole 20 mg; lansoprazole
30 mg vs omeprazole 20 mg; lansoprazole 15 mg vs omeprazole 20 mg; lansoprazole 30 mg vs
omeprazole 40 mg; lansoprazole 30 mg vs pantoprazole 40 mg; rabeprazole 20 mg vs omeprazole
20 mg; and rabeprazole 10 mg vs omeprazole 20 mg. Only one comparison found a statistically
significant difference between groups in the treatment of GORD: esomeprazole 40 mg vs omeprazole
20 mg (80% vs 67% response rate; P = 0.04; number needed to treat = 7). (This was the study used
as the basis for approval at Burnley).
Another comparison, in 1,306 patients, of equivalent doses of 20 mg esomeprazole vs 20 mg
omeprazole found no difference in endoscopic healing. Furthermore, the response rates for
omeprazole 20 mg in the 2 studies comparing it with esomeprazole 40 mg were 65% and 67% -considerably lower than in other comparisons looking at this dose, in which the success rate was
between 70% and 91%. The authors of the meta analysis concluded that there is no significant
difference between equivalent doses of all PPIs, including esomeprazole. NICE also does not
advocate the use of one PPI over another.
The decision to choose one over another should be based first on cost and second on
individual patient response. Omeprazole capsules (generic) or lansoprazole capsules (generic)
are proposed as the first line PPI’s across East Lancashire.
Place in Therapy
Management of resistant GORD in Primary care
GORD is only diagnosed by endoscopy, and if PPIs do not help these symptoms, an extra four
weeks of PPI therapy may be worthwhile. The dose of PPI may need to be increased or
esomeprazole initiated in grades C or D oesophagitis if symptoms do not resolve.
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Esomeprazole should not be initiated in primary care for the ongoing treatment of GORD,
however resistant.
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The formulary choices are omeprazole or lansoprazole first line.
•
Esomeprazole is not licensed for the treatment of dyspepsia.
Management of resistant GORD in Secondary care
The NICE clinical guideline does not address the management of endoscopically-proven GORD
within the secondary care setting (it is applicable to primary care only). However, the strategies
recommended by NICE for use in primary care should be exhausted by secondary care specialists in
all instances.
Where patients are resistant to use of high dose PPIs, use of esomeprazole could be considered by
a consultant gastroenterologist in severe GORD.
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Cost Comparisons
Cost for 28 days treatment [Prices from Drug Tariff –Feb 2010]
1.3 ANTISECRETORY DRUGS AND MUCOSAL PROTECTANTS
Esomeprazol (40mg od)
£25.19
Rabeprazole (20mg od)
£19.55
Misoprostol (200mcg qds)
£18.72
Esomeprazole (20mg od)
£18.50
Pantoprazole (40mg od)
£16.43
Sucralfate (1g qds)
£14.25
Losec® tablets (20mg od)
£11.60
Nizatidine (300mg od)
£9.81
Omeprazole tablets (20mg od)
£6.36
Cimetidine (400mg bd)
£6.27
Lansoprazole tablets (30mg od)
£5.50
Famotidine (40mg od)
Lansoprazole caps (30mg od)
£4.68
£2.79
Omeprazole caps (20mg od)
£1.76
Ranitidine (150mg bd)
£1.35
Ranitidine (300mg od)
£1.28
Doses given do
not imply
therapeutic
equivalence
£0.00
£5.00
£10.00
£15.00
£20.00
£25.00
£30.00
Cost (£) for 28 days treatment
N.B. Doses shown for general comparison and do not imply therapeutic equivalence and do not take into account licensed indications.
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East Lancashire Medicines Management Board representing East Lancashire Hospitals NHS Trust, NHS Blackburn with Darwen, NHS East Lancashire
Resource implications for East Lancashire
Guidance above to be read in conjunction with the manufacturer’s SPC.
For NHS use only – Not to be used or reproduced for commercial purposes
Red light = only to be prescribed within secondary care, specialist initiation only: GPs should not be asked to prescribe
Amber light = only to be initiated in secondary care with follow up prescribing by primary care without a shared care agreement
Amber light with Shared Care = only to be initiated in secondary care with follow up prescribing by primary care with a shared care agreement
Green light = prescribing is appropriate in both primary and secondary care within the specified conditions
Black list = Not included in the East Lancs Joint Formulary. Not recommended for prescribing in primary or secondary care. This may be
due to lack of good clinical evidence or more suitable alternatives available.
Fig 1a. North West SHA - prescribing frequency: Anti-secretory drugs and Mucosal protectants
April - September 2009
Liverpool
Knowsley
Halton & St.Helens
Manchester
Salford
Heywood, Middleton &
Tameside & Glossop
Ashton, Leigh & Wigan
Oldham
Blackpool
Bolton
Western Cheshire
Blackburn With Darwen
North West
Stockport
Wirral
North of England
Bury
East Lancashire
Warrington
North Lancashire
Central & Eastern
Sefton
Trafford
Cumbria
England
Central Lancashire
0
100
200
300
400
500
600
ADQs/100 Ulcer-healing STAR-PU
Lansoprazole
Omeprazole
Esomeprazole
Ranitidine Hydrochloride
Rabeprazole Sodium
Pantoprazole
Others
Audit
and monitoring
Primary care – Esomeprazole should be monitored quarterly via e-PACT data, and audit against East Lancs guidance on use of esomeprazole.
Secondary care – Esomeprazole prescribing should be monitored within secondary care on a three monthly basis.
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References
1.
NICE Clinical Guideline CG17 – Dyspepsia. Managing dyspepsia in adults in primary care. August 2004.
2.
Klok RM, Postma MJ, Van Hout BA, Brouwers JR. Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use. Aliment Pharmacol Ther 2003;17:1237-45.
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