nsaid regional audit group presentation · 2016. 5. 5. · nsaid regional audit group presentation...
TRANSCRIPT
NSAID Regional Audit Group
Presentation
Audit Group: Dr Richard Latten, Ruth Clark,
Dr Sarah Fradsham, Dr Seamus Coyle,
Claire Johnston
Thank you from the audit group for all who
participated in the data collection for this audit.
Our External/ Expert reviewers unfortunately cannot
make it today but have and will be involved in the
refinements of the S&G
Andrew Dickman, Dr Victor Pace.
Agenda
• Current Standards and Guidelines (CJ)
• Literature Review (SC)
• Proposed updated Standards and Guidelines
(RL)
• Questions and discussion
NSAIDs
Current Standards and Guidelines
Claire Johnston
Community SPC CNS
General principles
• Non-steroidal anti-inflammatory drugs (NSAIDs) consist
of a heterogenous group of compounds that can be
subdivided by virtue of their pharmacology;
-Non-selective NSAIDs inhibit both COX-1 and COX-2
receptors e.g. ibuprofen, naproxen.
-COX-2 selective NSAIDs display some selectivity for
COX-2 receptors but this diminishes as the dose
increases e.g. etodolac, meloxicam.
-COX-2 inhibitors specifically inhibit COX-2 receptors at
therapeutic doses whilst being COX-1 sparing e.g.
celecoxib, etoricoxib.
General principles
• All NSAIDs have significant cardiovascular and
gastrointestinal toxicity.
• Consider whether alternative treatment would be
appropriate (e.g. topical NSAIDs, paracetamol, tramadol).
• Prescribe the lowest possible dose of NSAID for the
shortest possible time necessary.
Current guidelines –
Cardiovascular Risk
• COX-2 inhibitors are contraindicated for use in patients with established ischaemic heart disease and/or cerebrovascular disease, and also in patients with peripheral arterial disease.[Level1]
• Despite conflicting evidence, non-selective NSAIDs and COX -2 selective are currently licensed for use in these groups of patients, although they should be used with caution. [Level 4]
Current guidelines- Renal
Dysfunction
• Renal function should be assessed prior to the introduction of an NSAID and within 7 days of starting treatment or increasing the dose.[Level 4]
• Care is required when prescribing NSAIDs for patients with heart failure, ascites or impaired renal function, particularly those who are dehydrated or have a low effective circulating volume. [Level 4]
Current guidelines- Renal
Dysfunction
• Long term administration of NSAIDs has been linked to papillary
necrosis and other renal injuries. Patients with impaired renal
function, heart failure, liver dysfunction, the elderly and those
taking diuretics and/or angiotensin-converting enzyme inhibitors
are at greatest risk from this reaction. Discontinuation of NSAIDs
therapy is usually followed by recovery to the pre-treatment
state.[Level 4]
• Use of NSAIDS in patients with advanced renal disease is not
recommended due to a lack of safety data from controlled
clinical studies. If NSAIDs are prescribed it is essential that renal
function is monitored closely.[Level 4]
Current guidelines-
Gastrointestinal Toxicity
• Patients at high risk of gastrointestinal side effects from NSAIDs include the following;[Level 4]
- Elderly (age>65 years),
-Previous upper gastroduodenal perforation,ulcers and bleeds.
-Concurrent use of aspirin, warfarin,corticosteroids or selective serotonin reuptake inhibitors (SSRIs)
-Patients receiving maximum doses of NSAIDs.
• Undesirable gastric side effects from celecoxib are significantly less than from non-selective NSAIDs although it is not clear whether this lower risk continues with long term use.[Level 4]
• In patients taking clopidogrel, it is advisable to use an H2 antagonist at a higher dose than usual e.g. ranitidine 300mgs bd. [Level 4]
Current Guidelines PPIs
• A PPI should be co-prescribed with a NSAID, regardless of
which actual drug is chosen. [Level 4]
• This is cost effective in the treatment of Osteoarthritis, but the
benefit of a PPI with a COX-2 inhibitor in other situations is
unclear. [Level 4]
• The relationship between H. pylori infection and NSAIDs in
duodenal pathology is complex. Eradication of H pYlori infection
may prevent peptic ulcer disease in patients who are naiive
users of NSAIDs. Patients receiving long term PPI treatment for
prevention of NSAID ulcers should be tested for H Pylori.
Eradiction of H Pylori will reduce the risk of accelerated loss of
specialised glands and atrophic gastritis. [Level 4]
Current Guidelines- PPI
• Appropriate PPIs and oral doses include:
- Esomeprazole 20mg od
- Lansoprazole 30mg od
- Omeprazole 20mg od
- Pantoprazole 40mg od
• Misoprostol is a synthetic prostaglandin analogue with gastric
anti-secretory and protective properties which can be used to
protect against NSAID-induced gastrointestinal damage. It is
more effective than PPIs but can be poorly tolerated. Side
effects include colic and diarrhoea. A suggested starting dose is
200mcg od, increasing by 200mcg every 1-2 days to a normal
dose of 200mcg qds.
Current Guidelines- Choice of
NSAID
• Before deciding which NSAID to use, the prescriber must first
asses patient risk factors for cardiovascular and gastrointestinal
toxicity (figure 29.1) [Level 4]
• Table 29.1 lists NSAIDs currently recommended for use.
• Table 29.2 lists additional NSAIDs that may be considered
second line options. [Level 4]
Current Guidelines-
Monitoring Effectiveness
• NSAIDs should be presribed for at least seven days before
reviewing their clinical effectiveness. The analgesic effect of the
drug becmes apparent within the first few days of treatment. The
anti-inflammatory response may take at least 2 weeks to
become evident. [Level 4]
• It may be appropriate to use an alternative NSAID before
concluding that NSAIDs are ineffective. [Level 4]
• Due to the increased risk of renal and gastroduodenal toxicity,
ketorolac should only be used for refractory pain. A PPI should
always be co-prescribed with ketorolac unless the patient is in
the dying phase. [Level 4]
Current Standards.
1. Cox-2 inhibitors are contra-indicated for use in patients with
existing ischaemic heart, peripheral vascular disease or
cerebrovascular disease [GradeB]
2. In patients with existing cardiovascular disease, alternate
analgesia should be considered before introducing a non-
selective NSAID or a COX-2 selective NSAID. If NSAID’s are to
be used the lowest dose possible should be prescribed and the
patient should be reviewed within 7 days. [Grade D]
3. It may be appropriate to use an alternative NSAID before
concluding that NSAIDs are ineffective. [Grade D]
Current Standards
4. Patients with risk factors for gastrointestinal toxicity should be
prescribed proton pump inhibitors or misoprostol for gastric
protection [Grade B]
5. A PPI should be prescribed for all patients receiving
subcutaneous NSAID’s, unless they are in the dying
phase.[Grade D]
6. Renal function should be assessed prior to the introduction of a
NSAID and within 7 days of starting treatment or increasing the
dose. [Grade D]
Table 29.1- NSAIDS currently
recommended for use
Class
of
NSAID
Name of
drug
Oral dose CSCI over
24 hours
Additional notes
Non-
selective
Naproxen 500mg bd n/a Suitable 1st line choice, together
with PPI for patients with CV risk
Non-
selective
Ibuprofen 400mg-
800mg tds
n/a Low dose brufen(<1200mgs)
suitable1st line choice, together
with PPI, for patients with CV risk.
If low dose aspirin is co-
prescribed, ibuprofen should be
given at least 8 hours before or
30 minutes after. Alternatively,
Change aspirin to clopidogrel.
COX-2
inhibitor
Celecoxib 100-200mg
bd
n/a Suitable 1st line choice in patients
at high risk of GI toxicity and low
CV risk. PPI should be co-
prescribed in high GI risk
patients.
Table 29.2. Additional NSAIDs avaliable for
use [Level 4]
Class of
NSAID
Name of
drug
Oral
dose
CSCI
over 24
hours
Additional notes
Non-
selective
Diclofenac
sodium
50mg tds
75mg m/r
bd
Painful.
Dose
150mg
daily
150mg daily via rectal route. Diclofenac is
associated with similar thrombotic risk to
COX-2 inhibitors
Non-
selective
Nabumetone 500mg
od-1g bd
n/a/ Lowest GI risk of all non-selective NSAIDS.
Some units may user first line.
Non-
selective
Ketorolac n/a/ 30mg-
90mg
Can give 10mg stat subcutaneous dose.
Carries greater risk of renal and
gastrointestinal toxicity compared to other
NSAIDs. Due to the propensity for toxicity,
the continued need for a CSCI of ketorolac
should be reviewed on a weekly basis.
Non
selective
Piroxicam
melt
20mg od
S/L
Increased risk of GI toxicity and
serious skin reactions. Not to be
used for first line treatment.
Table 29.2 Cont
Class of
NSAID
Name of
drug
Oral dose CSCI over
24 hours
Additional notes
COX-2
selective
Etodolac 600mg m/r od n/a n/a
COX-2
inhibitor
Etoricoxib 60mg-120mg
od
n/a NICE do not recommend
etoricoxib for first line
use in osteoarthritis. For
this reason, consider as
2nd line choice.
Consider whether alternative treatment would be appropriate
Assessment of cardiovascular (CV) history
No CV History CV History
Assessment of gastrointestinal (GI)
risk factors
Assessment of gastrointestinal (GI)
risk factors
Low GI Risk >1 GI Risk Low GI Risk >1 GI Risk
List A List B List C List D
Figure 29.1 – Flow diagram of NSAID
choice
Table 29.3. Choice of NSAID according to
CV history and GI risk factors
Step List A
No CV history
No GI risk
List B
No CV history
GI risk
List C
CV history
No GI risk
List D
CV history
GI risk
1 Alternative analgesia
e.g. topical NSAID,
paracetamol, tramadol
Alternative analgesia
e.g. topical NSAID,
paracetamol, tramadol.
Alternative analgesia
e.g. topical NSAID
paracetamol,
tramadol.
Alternative analgesia
e,.g. topical NSAID,
paracetamol, tramadol.
2 Low dose ibuprofen
(<1200mg/day) +PPI or
Nabumetpone plus PPI
COX-2 Inhibitor
e.g. celecoxib + PPI
Low dose ibuprofen
(<1200mg/day) +PPI
or naproxen +PPI
Low dose ibuprofen
(<1200mg/day) +PPI or
naproxen + PPI
3 Non-selective NSAID
e.g. diclofenac + PPI or
naproxen + PPI
COX-2 inhibitor e.g.
etoricoxib + PPI
Non selective NSAID
e.g. nabumetone +
PPI
Non selective NSAID e.g.
nabumetone + PPI
4 COX-2 selective
NSAID e.g. etodolac +
PPI
Low dose ibuprofen
(1200mgs/day) + PPI or
nabumetone plus PPI
5 COX-2 inhibitor e.g.
celecoxib
COX-2 selective NSAID
e.g. etodolac + PPI
NSAID Audit
-Literature Review
Dr Seamus Coyle
Academic Clinical Fellow
Overview
• Literature search
• Rational of NSAIDs
– including indications
• NSAIDs in non-cancer conditions
• Topical NSAIDs
• Risks/Side effects of NSAIDs
• Palliative Overview
Literature Search
• Literature Survey of NSAIDs over the last 5
years
– 105 NSAID review articles
• all articles for ‘NSAIDs and Palliative care’
• The Cochrane library
• NICE guidelines
Rational of NSAIDs
• NSAIDs more effective than placebo for cancer pain
– Cancer pain = as a result of the cancer itself, a side effect of therapy or procedures or unrelated to the cancer
• Clear evidence to support safety or efficacy of one NSAID over another is lacking
• Slight but statistically significantly advantage (9 out of 14 papers) combining Paracetamol with a NSAID compared with either single entity
NSAIDs or Paracetamol, alone or combined with opioids for cancer pain Cochrane Review 2011 McNicol ED Strassels S, Goudas L, Lau J, Carr DB
• 13 out of 14 studies found no difference or low clinical difference when combining an NSAID plus an opioid versus either drug alone. 4 papers increased efficacy with increased dose - the majority of studies were of less than 7 days duration
• No studies addressed use of COX2 inhibitors to manage cancer pain
• Meta-analysis of 4 trials demonstrated significantly lower proportion of patients reported adverse events while being administered NSAIDs vs opioids (OR=0.38 [95% CI, 0.15 to 0.97]
NSAIDs or Paracetamol, alone or combined with opioids for cancer pain Cochrane Review 2011 McNicol ED Strassels S, Goudas L, Lau J, Carr DB
• Short duration of studies undermines generalisation of their findings on efficacy and safety of NSAIDs for cancer pain
• the use of NSAIDs for cancer pain is widely recommended, the long term safety profile of NSAIDs in patients with cancer has not been established in a randomised study.
• WHO recommends addition of a 'weak' opioid for mild to moderate pain. ..findings do not substantiate this recommendation. It may be advisable to increase to a maximum acceptable dose of their NSAIDs (or adjuvant drug) before the addition of, or replacement with, an opioid.
NSAIDs or Paracetamol, alone or combined with opioids for cancer pain Cochrane Review 2011 McNicol ED Strassels S, Goudas L, Lau J, Carr DB
Advice to Healthcare professionals
• Patients should use the lowest effective dose and the shortest duration of NSAID treatment necessary to control symptoms, and the need for long-term treatment should be reviewed periodically
• NSAIDs increase the risk of Cardiovascular events but that the balance of benefits to risks remained favourable
MHRA Public Assessment Report Jan 2010
NSAIDs in non-cancer conditions
Pharmacological management of osteoarthritis*
• When paracetamol/topical NSAIDs ineffective for pain
relief,
– substitution with an oral NSAID/COX-2 inhibitor
should be considered.
• Where paracetamol/topical NSAIDs provide insufficient
pain relief
– addition of an oral NSAID/COX-2 inhibitor to
paracetamol should be considered.
• Oral NSAIDs/COX-2 inhibitors should be used at the lowest
effective dose for the shortest possible period of time.
*Pharmacological management of osteoarthritis NICE Guidelines 2008
Pharmacological management of
osteoarthritis*
• First choice should be either a standard NSAID or a
COX-2 inhibitor (other than etoricoxib 60 mg)
– co-prescribed with a PPI
*Pharmacological management of osteoarthritis NICE Guidelines 2008
Pharmacological management of
osteoarthritis*
• All oral NSAIDs/COX-2 inhibitors have analgesic
effects of a similar magnitude but vary in their potential
gastrointestinal, liver and cardio-renal toxicity;
– take into account individual patient risk factors,
including age.
– appropriate assessment and/or ongoing monitoring of
these risk factors.
*Pharmacological management of osteoarthritis NICE Guidelines 2008
Pharmacological management of
osteoarthritis*
• When patient needs to take low-dose aspirin and pain
relief is ineffective or insufficient
• consider other analgesics before substituting or adding
an NSAID / COX-2 inhibitor (with a PPI)
*Pharmacological management of osteoarthritis NICE Guidelines 2008
Oral analgesics
• Paracetamol and/or topical non-steroidal anti-
inflammatory drugs (NSAIDs) should be considered ahead
of oral NSAIDs / COX-2 inhibitors or opioids.
• If paracetamol or topical NSAIDs are insufficient for pain
relief then the addition of
– opioid analgesics should be considered.
• Risks and benefits should be considered
• particularly in the elderly
Pharmacological management of osteoarthritis NICE Guidelines 2008
NSAIDs and highly selective COX-2 inhibitors
• Increased role for COX-2 inhibitors, with an increased
awareness of all potential adverse events
(gastrointestinal, liver and cardio-renal) and a
recommendation to co-prescribe a PPI.*
• based on up-to-date evidence on efficacy, adverse
events, current costs and an expanded health-
economic analysis of cost effectiveness.*
*Pharmacological management of osteoarthritis NICE Guidelines 2008
NSAIDs may be tolerated in patients with mild
chronic liver disease but should be avoided in
all patients with cirrhosis because of increased
risk of hepatorenal syndrome
Pain Management in the Cirrhotic patient Chandok Watt 2010 Mayo Clin Proc.
2010 May;85(5):451-8.
Topical NSAIDs
• Topical NSAIDs can provide good levels of pain relief in acute
conditions such as sprains, strains and overuse injuries*
– Probably similar to that provided by oral NSAIDs.
– Little difference in analgesic efficacy between diclofenac, ibuprofen,
ketoprofen and piroxicam but indomethacin is less effective, and
benzydamine is no better than placebo.
– No increased incidence of local reactions compared to placebo
– Do not cause systemic problems
* Topical NSAIDs for acute pain in adults (review) The Cochrane Collaboration 2012
• Topical NSAIDs can provide good levels of pain relief*
– without the systemic adverse events associated with oral NSAIDs
– when used to treat acute musculoskeletal conditions.
• No serious adverse events reported in studies reviewed*
* Topical NSAIDs for acute pain in adults (review) The Cochrane Collaboration 2012
Risks/Side effects of NSAIDs
• All NSAID users may be at an increased CV risk, irrespective of their baseline risk for cardiovascular illness or the duration of NSAID use
MHRA Public Assessment Report Jan 2010
• Since 2006 2 important studies have been published which examine the risk of thrombotic cardiovascular events, such as MI in association with NSAIDs. (non-selective NSAIDs and COX-2 inhibitors) – UK THIN (The Health Improvement Network)
– Danish group
MHRA Public Assessment Report Jan 2010
• Both studies found a very small increase in the risk of CVS events..that may apply to all users of NSAIDs, not only those with baseline CVS risk factors ..after a relatively short-term NSAID use (that may increase with increasing duration of use). association with the following specific NSAIDs;
• celecoxib (any dose); high dose diclofenac (>150mg/day); high dose ibuprofen (>1200mg/day)
• No detectable effect on CV risk was demonstrated for another specific NSAID, naproxen, at any dose.
MHRA Public Assessment Report Jan 2010
• Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.
• Cardiovascular outcomes with etoricoxib and diclofenac in patients
with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
• Cannon et al The Lancet 2006 Vol 368 p1771 – 1781
Rationale for discontinuing Cox-2 inhibitors*
• VIGOR Study – significantly higher incidence of
cardiovascular thrombotic events with rofecoxib cf
naproxen (Bombardier et al NEJM 2000) 5 fold increase
risk of MI
• APPROVE study confirmed above – evaluated
adenomatous polyps in patients treated with rofecoxib ct
placebo. 2 fold increase MI risk (Bresalier et al NEJM 2005)
• Meta-analysis of Rofecoxib (Juni Lancet 2004)
• Rofecoxib and valdecoxib withdrawn * Review of the CVS safety of CoxiBs compared to NSAIDs Moodley Cardiovasc J Afr
2008 Mar-Apr;19(2):102-7.
Rationale for discontinuing Cox 2 inhibitors*
• No increase in cardiovascular events or all cause mortality
was observed for celecoxib vs diclofenac, ibuprofen and
naproxen (Varas-Lorenzo et al 2007)
• Pooled analysis no increase CVS events with celecoxib but at
higher doses higher risk of MI (Juni et al Br Med J 2002)
• risk of death and recurrent CHF combined was higher in
patients prescribed NSAIDs or rofecoxib than in those
prescribed celecoxib
* Review of the CVS safety of CoxiBs compared to NSAIDs Moodley Cardiovasc J Afr 2008
Mar-Apr;19(2):102-7.
• Cox-2 inhibitors appear to be prescribed preferentially to patients
who were at an increased risk of cardiovascular events compared
with patients prescribed non-specific NSAIDs*
• When the overall risk of CVS complications is relatively low and
an anti-inflammatory agent is required, current evidence suggests
that celecoxib is an agent of choice because of its lower
cardiovascular toxicity potential compared to NSAIDs and other
Cox-2 inhibitors *
• Most patients, particularly the young, can benefit from NSAIDs
without the risk of serious adverse GI or CVS events... previous
history of serious GI complications and the elderly .. do require
alternatives*
* Review of the CVS safety of CoxiBs compared to NSAIDs Moodley Cardiovasc J Afr
2008 Mar-Apr;19(2):102-7.
• South African Rheumatoid Arthritis Association Guidelines
Nov 2005 - Cox-2 inhibitors for elderly patients (>60) with
previous gastropathy and those on warfarin and / or
corticosteroids, providing they do not have
contraindications.
• Caution prescribing Cox-2 inhibitors for patients with risk
factors for heart disease
• Celecoxib does not increase small intestinal permeability
and does not cause lower intestinal bleeding
* Review of the CVS safety of CoxiBs compared to NSAIDs Moodley Cardiovasc J Afr
2008 Mar-Apr;19(2):102-7.
A Palliative Overview
• There were no studies with NSAIDs and
Palliative Care / EOL care
• Long term safety profile of NSAIDs in patients
with cancer has not been established in a
randomised study.
• No studies addressed use of COX2 inhibitors
to manage cancer pain
A Palliative Overview
• There were no studies with NSAIDs and
Palliative Care / EOL care
• Long term safety profile of NSAIDs in patients
with cancer has not been established in a
randomised study.
• No studies addressed use of COX2 inhibitors
to manage cancer pain
NSAIDs
Proposed updated Standards and
Guidelines
Dr Richard Latten
Consultant in Palliative Medicine
General Principles
• Cyclo-oxygenase (COX) 1 and 2 are involved in the
inflammatory pathways. COX 1 is primarily involved in
homeostatic functions including platelet function,
gastroprotection and the maintenance of renal function.
COX 2 is primarily involved in inflammation but also has
some homeostatic functions . See figure 29.1
• Figure 29.1 Will give a summary of the COX 1
and COX 2 pathways
Figure 29.1 – Cyclo-oxygenase pathways
55
Arachidonic Acid
COX- 1 COX- 2
HOMEOSTATIC FUNCTIONS
e.g gastroprotection, renal function, platelet aggregation
INFLAMMATION
General principles
• Non-steroidal anti-inflammatory drugs (NSAIDs) consist
of a heterogenous group of compounds that can be
subdivided by virtue of their pharmacology;
-Non-selective NSAIDs inhibit both COX-1 and COX-2
receptors e.g. ibuprofen, naproxen.
-COX-2 selective NSAIDs display some selectivity for
COX-2 receptors but this diminishes as the dose
increases e.g. etodolac, meloxicam.
-COX-2 inhibitors specifically inhibit COX-2 receptors at
therapeutic doses whilst being COX-1 sparing e.g.
celecoxib, etoricoxib.
General principles
• All NSAIDs have cardiovascular and gastrointestinal
toxicity.
• Indications for NSAIDs include:
– Bone Pain
– Musculoskeletal Pain
– Inflammatory conditions (including OA and RA)
– Paraneoplastic Pyrexia and Sweating
– Fever
General principles
• The WHO analgesic ladder recommends NSAIDs be
considered as an adjunct in each step if appropriate.
• It is recommended that in the first instance consideration
is made as to whether an alternative treatment would be
appropriate (e.g. topical NSAIDs, paracetamol, tramadol,
?Pregabalin).
• It is recommended that the lowest possible dose of NSAID
be precribed for the shortest possible time necessary.
Guidelines – Cardiovascular Risk
• COX-2 inhibitors are contraindicated for use in patients with established ischaemic heart disease and/or cerebrovascular disease, and also in patients with peripheral arterial disease.[Level1]
• Despite conflicting evidence, non-selective NSAIDs and COX -2 selective are currently licensed for use in these groups of patients, although they should be used with caution. [Level 4]
• Diclofenac is associated with similar thrombotic risks as COX 2 inhibitors. [Level 1]
• All NSAIDs are contraindicated in patients with severe heart failure. [Level 1]
Guidelines – Cardiovascular Risk
• Etoricoxib may be associated with more frequent and
severe effects on blood pressure than some other COX-2
inhibitors and NSAIDs, particularly at high doses.
Etoricoxib treatment should therefore not be initiated in
patients whose hypertension is not under control and
careful monitoring of blood pressure is advised for
patients taking etoricoxib. [Level 1]
• NSAIDs differ in their effect on platelet function and bleeding
time. Some non-selective NSAIDs whilst not having an
antiplatelet effect do interfere with the action of Aspirin. [Level 1]
Guidelines- Renal
Dysfunction
• Renal function should be assessed prior to the introduction of an NSAID and within 7 days of starting treatment or increasing the dose.[Level 4]
• Care is required when prescribing NSAIDs for patients with heart failure, ascites or impaired renal function, particularly those who are dehydrated or have a low effective circulating volume. [Level 4]
Guidelines- Renal
Dysfunction
• Long term administration of NSAIDs has been linked to papillary
necrosis and other renal injuries. Those patients at greater risk
of this reaction include: [Level 4]
– impaired renal function,
– heart failure,
– liver dysfunction,
– the elderly
– Concurrent use of angiotensin-converting enzyme
(ACE) inhibitors, diuretics or Angiotensin 2 receptor
blockers .
• Discontinuation of NSAIDs therapy is usually followed by
recovery to the pre-treatment state.[Level 4]
Guidelines- Renal
Dysfunction
• Use of NSAIDS in patients with advanced renal disease is
not recommended due to a lack of safety data from
controlled clinical studies. If NSAIDs are prescribed it is
essential that renal function is monitored closely.[Level 4]
Guidelines- Gastrointestinal
Toxicity
• Patients at high risk of gastrointestinal side effects from
NSAIDs include the following;[Level 4]
- Elderly (age>65 years),
-Previous upper gastroduodenal perforation,ulcers
and bleeds.
-Concurrent use of aspirin, warfarin,corticosteroids or
selective serotonin reuptake inhibitors (SSRIs)
-Patients receiving maximum doses of NSAIDs.
Guidelines- Gastrointestinal
Toxicity
• Of the non selective NSAIDs, low dose ibruprofen is
associated with the lowest GI risk.[Level 1]
• Undesirable gastric side effects from celecoxib are
significantly less than from non-selective NSAIDs
although it is not clear whether this lower risk continues
with long term use.[Level 4]
Guidelines- Gastrointestinal
Toxicity
• In patients taking clopidogrel, it is advisable to use an H2
antagonist at a higher dose than usual e.g. ranitidine
300mgs bd or Lansoprazole 30mg od for gastric
protection. Omeprazole and Esomeprazole should be
avoided due to the potential for interactions. [Level 4]
Guidelines PPIs
• A PPI should be co-prescribed with a NSAID including COX-2
inhibitor, regardless of which actual drug is chosen. [Level 4]
• The relationship between H. pylori infection and NSAIDs in
duodenal pathology is complex. Eradication of H pYlori infection
may prevent peptic ulcer disease in patients who are naiive
users of NSAIDs. Patients receiving long term PPI treatment for
prevention of NSAID ulcers should be tested for H Pylori.
Eradiction of H Pylori will reduce the risk of accelerated loss of
specialised glands and atrophic gastritis. [Level 4]
Guidelines- PPI
• Appropriate PPIs and oral doses include:[Level 4]
- Lansoprazole 30mg od
- Omeprazole 20mg od
- Pantoprazole 40mg od
- Esomeprazole 20mg od
• Misoprostol is a synthetic prostaglandin analogue with gastric anti-secretory and protective properties which can be used to protect against NSAID-induced gastrointestinal damage. It is more effective than PPIs but can be poorly tolerated. Side effects include colic and diarrhoea. A suggested starting dose is 200mcg od, increasing by 200mcg every 1-2 days to a normal dose of 200mcg qds. Some combined preparations are avaliable e.g Napratec (Naproxen and Misoprostol). [Level 1]
Guidelines- Choice of NSAID
• Before deciding which NSAID to use, the prescriber must
first asses patient risk factors for cardiovascular and
gastrointestinal toxicity (figure 29.1) Figure 29.2 then
recommends first line and second line options for NSAIDs
depending on these risk factors. [Level 4]
• Table 29.1 lists NSAIDs currently avaliable for use along
with cautions and recommended doses.[Level 4]
Guidelines- Monitoring
Effectiveness
• NSAIDs should be presribed for at least seven days before
reviewing their clinical effectiveness. The analgesic effect of the
drug becmes apparent within the first few days of treatment. The
anti-inflammatory response may take at least 2 weeks to
become evident. [Level 4]
• It may be appropriate to use an alternative NSAID before
concluding that NSAIDs are ineffective. [Level 4]
• Due to the increased risk of renal and gastroduodenal toxicity,
ketorolac should only be used for refractory pain. A PPI should
always be co-prescribed with ketorolac unless the patient is in
the dying phase. [Level 4]
Standards.
1. Cox-2 inhibitors are contra-indicated for use in patients with
existing ischaemic heart, peripheral vascular disease or
cerebrovascular disease. All NSAIDS are contraindicated for
use in patients with severe heart failure.[GradeB]
2. In patients with existing cardiovascular disease, alternate
analgesia should be considered before introducing a non-
selective NSAID or a COX-2 selective NSAID. If NSAID’s are to
be used the lowest dose possible should be prescribed and the
patient should be reviewed within 7 days. [Grade D]
3. It may be appropriate to use an alternative NSAID before
concluding that NSAIDs are ineffective. [Grade D]
Standards
4. All patients prescribed NSAIDS should be prescribed proton
pump inhibitors or misoprostol for gastric protection [Grade B]
5. A PPI should be prescribed for all patients receiving
subcutaneous NSAID’s, unless they are in the dying
phase.[Grade D]
6. Renal function should be assessed prior to the introduction of a
NSAID and within 7 days of starting treatment or increasing the
dose. [Grade D]
Consider whether alternative treatment would be appropriate e.g topical
NSAID, paracetamol
Assessment of cardiovascular (CV) history
No CV History CV History
Assessment of gastrointestinal (GI) risk
factors
Assessment of gastrointestinal (GI) risk
factors
Low GI Risk >1 GI Risk Low GI Risk 1 > GI Risk
Figure 29.2 – Flow diagram of NSAID choice
74
Involve patient / relative in discussions regarding benefit vs risk of proposed NSAID
Step List A
No CV history
Low GI risk
List B
No CV history
GI risk
List C
CV history
Low GI risk
1 Low dose
ibuprofen
(<1200mg/day)
+PPI or
Nabumetone plus
PPI
COX-2 Inhibitor
e.g. celecoxib + PPI
Low dose ibuprofen (<1200mg/day) +PPI or
naproxen +PPI
2 Non-selective
NSAID e.g.
naproxen + PPI
COX-2 inhibitor e.g.
etoricoxib + PPI
Non selective NSAID e.g. nabumetone + PPI
Table 29.1- NSAIDS currently avaliable
for use
Class of
NSAID
Name of
drug
Route Dose Additional notes
COX-2
inhibitor
Celecoxib Oral 100-200mg bd Suitable 1st line choice in
patients at high risk of GI
toxicity and low CV risk. PPI
should be co-prescribed in
high GI risk patients.
COX-2
selective
Etodolac Oral 600mg m/r od n/a
COX-2
inhibitor
Etoricoxib Oral 30-90mg od NICE do not recommend
etoricoxib for first line
use in osteoarthritis. For
this reason, consider as
2nd line choice. May be
associated with
hypertension.
Table 29.1- NSAIDS currently avaliable for
use
Class of
NSAID
Name of
drug
Oral dose Dose Additional notes
Non-
selective
Diclofenac
sodium
Oral 50mg bd
75mg m/r bd
NOT RECOMMENDED FOR USE
DUE TO CARDIOVASCULAR AND
GI RISKS
Non-
selective
Ibuprofen Oral 400mg tds Low dose ibruprofen (<1200mg)
suitable1st line choice, together with
PPI, for patients with CV risk. If low
dose aspirin is co-prescribed,
ibuprofen should be given at least 8
hours before or 30 minutes after.
Alternatively, Change aspirin to
clopidogrel.
Non-
selective
Ketorolac S/C 30mg-90mg
via syringe
pump over
24hrs
Can give 10mg stat subcutaneous
dose. Carries greater risk of renal and
gastrointestinal toxicity compared to
other NSAIDs. Due to the propensity
for toxicity, the continued need for a
CSCI of ketorolac should be reviewed
on a weekly basis.
Table 29.1 NSAIDs currently avaliable for
use [Level 4]
Class of
NSAID
Name of
drug
Route Dose Additional notes
Non-
selective
Nabumetone Oral 500mg od-
1g bd
Lowest GI risk of all non-selective
NSAIDS. Some units may user first line.
Non-
selective
Naproxen Oral 500mg bd Suitable 1st line choice, together with PPI
for patients with CV risk
Non
selective
Piroxicam
melt
Sublingual 20mg od Increased risk of GI toxicity and
serious skin reactions. Not to be
used for first line treatment.