NSAIDs - Centre for Medicines Optimisation

Actions for Commissioning Teams
Avoiding Hospital Admissions Due to
Information for Practices
March 2012
This presentation updates a previous publication
“APT 14 – Admissions Avoidance”
from September 2009
Actions for Commissioning Teams
Why are we looking at this?
In 2010/2011 there were 2,043,532 admissions to hospitals in
the West Midlands.
Data: HES
Some hospital admissions could be avoided including some of
those related to adverse drug reactions (ADRs).
o Systematic review (2009) of observational studies conducted in
UK found that approximately 6.5 to 7.5% of admissions are
medication-related.1 Approx 69% of these considered avoidable.
ADRs affect patients’ health and wellbeing and are associated
with significant costs (costs of care and costs of potential
Actions for Commissioning Teams
What are we covering?
The following slides provide information on:
Adverse drug reactions
o Causes
o Who is at risk?
o Tips for safe prescribing and safe repeat prescribing issues
Specific medicines causing ADRs
Antidiabetic drugs
Actions for Commissioning Teams
Common reasons for medication-related hospitalisation are2:
o gastrointestinal tract (GI) problems (GI bleeding, constipation and
o cardiovascular (CV) symptoms
o respiratory symptoms (associated with diuretics, respiratory
drugs, beta-blockers or NSAIDs)
o poor glycaemic control
Actions for Commissioning Teams
ADRs: which drugs are most
commonly implicated?
Drugs frequently implicated in preventable hospital
Non-steroidal anti-inflammatory drugs (NSAIDs)
Antiplatelets (e.g. low dose aspirin)
Anticoagulants (e.g. warfarin)
Angiotensin converting enzyme (ACE) inhibitors/angiotensin
receptor II blockers (ARBs)
o Antidiabetic drugs
o CNS drugs (e.g. antiepileptics, opioid analgesics and
o Digoxin
Systematic review found four drug classes account for >50% of
preventable drug-related admissions3:
o NSAIDs, antiplatelets , anticoagulants, diuretics.
Actions for Commissioning Teams
Causes of preventable
Incorrect selection of drug, dose, frequency or route
“High risk” prescribing (e.g. use of drugs when there are
Inadequate medication monitoring
Inadequate medication review
Badly designed repeat prescribing systems
Patient non-adherence
Poor communication across organisations e.g. community (GP
and wider healthcare teams, pharmacy and care home),
hospitals and social care
Actions for Commissioning Teams
ADRs: which patients are most at
Risk of an ADR resulting in hospital admission is particularly
high in the following groups2,5:
o Elderly
o Patients with multiple co-morbidities
o Patients taking several drugs
o Patients with acute medical problems
o Patients with impaired cognition
o Patients with poor adherence to prescribed medication
o Patients with impaired renal function
Actions for Commissioning Teams
Tips for safe
Before prescribing a drug, carefully assess potential harms and
benefits and consider whether it is appropriate for the patient.
o Consider co-morbidities or allergies, drug adverse effects and
o Is the patient taking any OTC preparations that could interact with
the prescribed agent?
o Consider non-pharmacological interventions.
Involve patients in prescribing decisions and inform them of
potential adverse effects.
Explain clearly directions for use.
o Will the patient be able to read the packet/labels or use the
Use appropriate formulations.
o e.g. If the patient has difficulty swallowing, consider liquid /
dispersible formulations.
Actions for Commissioning Teams
Tips for safe
Review medication regularly
o Medicines which appear to have no benefit or have unacceptable
side effects should be discontinued.
Undertake essential laboratory tests regularly
Ensure repeat prescribing system is efficient, effective and safe
(see slide 10)
Ensure effective communication between healthcare interfaces
(primary/secondary care or medical/social care)
o Review process for actioning medication changes
Actions for Commissioning Teams
Tips for safe repeat prescribing
Ensure robust and up-to-date repeat prescribing policy is in
place (and the relevant people have read and understood it)
Only appropriately qualified prescribers should put
medications on repeat prescription
Set an appropriate medication review date
Ensure there is an appropriate process for making changes to
the repeat prescription lists
Ensure safe system for ordering repeats (i.e. by repeat slip,
dedicated email address)
o Oral requests for repeat prescriptions should be discouraged.
Actions for Commissioning Teams
Tips for safe repeat prescribing
When a repeat prescription is requested, an administrative
check should be done to determine:
o Is the drug within its review date?
o Is the request earlier or later than expected (i.e. is the drug being
over-ordered or under-ordered).
All medicines should have full instructions (not “as directed”)
and be linked to an indication.
Medicines such as sleeping tablets, antibiotics, opioid
painkillers, benzodiazepines should not be put on repeat.
National Patient Safety Alerts (NPSA) indicate that some
medicines (e.g. warfarin, methotrexate, DMARDs) will need
robust systems in place before a prescription is issued.
Actions for Commissioning Teams
NSAIDs (standard and coxibs) are associated with:
o CV adverse outcomes (including myocardial infarction and
o GI adverse events (including GI bleeding).7
o renal adverse events (including acute renal failure).7
Risk of CV adverse events particularly high with coxibs and
diclofenac. Low-dose ibuprofen (≤ 1200 mg/day) and naproxen
(1000 mg/day) associated with lowest CV risk.6
Concomitant use of an NSAID/coxib with either a selective
serotonin reuptake inhibitor (SSRI), an anticoagulant, an
antiplatelet drug or a corticosteroid increases GI bleeding risk.
Concomitant use of an NSAID/coxib with either an ACE
inhibitor, ARB, diuretic or aliskiren increases risk of renal
impairment or failure.
Actions for Commissioning Teams
Avoiding ADRs: NSAIDS
Before initiating an NSAID (traditional or coxib), consider
alternative treatments.
For non-specific low back pain consider:
o structured exercise programmes, manual therapy or acupuncture8
For patients with osteoarthritis (OA), therapy should include9:
o access to appropriate information, activity and exercise,
interventions to help weight loss.
o self-management strategies (e.g. suitable footwear, heat or cold
packs, tens).
First choice analgesic for OA is paracetamol.9 Check whether a
full trial of regular paracetamol has been tried previously.
For knee or hand OA: topical NSAIDs and/or paracetamol
should be considered ahead of oral NSAIDs/coxibs or opioids.9
Actions for Commissioning Teams
Avoiding ADRs: NSAIDS
If an NSAID is necessary, use ibuprofen (1,200 mg/day or less)
as first line and naproxen (1,000 mg/day) as second-line.
Prescribing should be based on safety profiles of individual
NSAIDS/coxibs and individual patient risk profiles (e.g. GI, CV
and renal).
Use the lowest effective dose for the shortest possible time.
Only prescribe one NSAID at a time and check patient is not
also using an OTC NSAID.
Actions for Commissioning Teams
Avoiding ADRs: NSAIDs
Is gastroprotection indicated?
o NICE recommends that all patients prescribed an NSAID/coxib for
OA9 or rheumatoid arthritis (RA) 10 should also be prescribed a
proton pump inhibitor (PPI).
o NICE recommends that patients over 45 years prescribed an
NSAID/coxib for non-specific back pain should be co-prescribed
a PPI.8
Consider potential drug interactions before co-prescribing
NSAIDs with other medicines.
o e.g. ACE inhibitors, ARBs, aliskiren, diuretics, SSRIs,
corticosteroids, anticoagulants.
Renal function should be careful monitored if NSAIDs are
prescribed for patients at risk of renal impairment or renal
failure (particularly elderly).
Actions for Commissioning Teams
Avoiding ADRs: NSAIDs
Etoricoxib should only be prescribed in line with MHRA and
NICE guidance.11
o Patients with uncontrolled hypertension should not be prescribed
o Blood pressure should be monitored two weeks after treatment is
initiated and regularly thereafter.
Review all NSAID treatment regularly.
o Could the NSAID/coxib be discontinued?
o If continued use is necessary considering switching to ibuprofen
or naproxen (if not already using either of these NSAIDs).
Commissioners and PCT/GP Clinical Commissioning Groups
o ensure that systems are in place to regularly review
appropriateness of NSAID prescribing, particularly in people at
high risk of serious GI and CV adverse events.
Actions for Commissioning Teams
Avoiding ADRs: diuretics
Diuretics are often overused in the elderly.
Diuretics should not be used for chronic treatment of simple
gravitational oedema.12
o If prescribed for this purpose, do not put on repeat.
o Simple gravitational oedema will usually respond to increased
movement, raising the legs and support stockings.
The use of diuretics for the treatment of hypertension or heart
failure should be regularly reviewed.12
o Assess hydration status, renal function and serum electrolytes.
Actions for Commissioning Teams
Avoiding ADRs: aspirin
Antiplatelet drugs including aspirin increase the risk of
haemorrhagic complications, particularly GI bleeding.13
Risk of major bleeding events is increased with concurrent use
of anticoagulants or NSAIDs.
Aspirin is not licensed for the primary prevention of vascular
o MHRA advises that if used in primary prevention, the balance of
benefits and risks should be considered, particularly the presence
of risk factors for vascular disease (including conditions such as
diabetes) and the risk of GI bleeding.
If aspirin is indicated
o use 75 mg daily unless a higher dose is indicated.
o For patients at high-risk of GI complications, a PPI can be
Actions for Commissioning Teams
Avoiding ADRs: clopidogrel
No strong evidence that clopidogrel is safer than aspirin.
Patients taking clopidogrel who are at high risk of GI bleeding
may be co-prescribed a gastroprotective agent.15
o Consider PPIs other than omeprazole or esomeprazole*. Other
gastroprotective agents such as H2-receptor antagonists (except
cimetidine) or antacids may be more suitable for some patients.
*Omeprazole or esomeprazole may reduce antiplatelet action of clopidogrel
Actions for Commissioning Teams
Avoiding ADRs:
Before issuing prescription check:
o Is INR being monitored regularly?
o Is the INR level okay?
o Does the patient understand what dose to take?
Watch out for interacting drugs
o Care should be taken when starting, stopping or altering dose of an
interacting drug.
Any disease states or lifestyle changes that will affect INR?
Make sure patient’s handheld record is kept up-to-date.
Ensure there are written safe practice procedures for
administration in social care settings e.g. care homes.
Risk assess monitored dosage systems.
o Dose changes more difficult using these systems.
o Use of anticoagulants in these dosage systems not recommended.
Actions for Commissioning Teams
Diabetes is a chronic and progressive illness. If untreated or
not managed well, patients with diabetes may develop serious
o Short-term complications include hypoglycemia, hyperglycemia,
ketoacidosis, and hyper-osmolar syndrome.
o Long-term complications include heart disease, kidney disease,
neuropathy, diseases of the eyes, peripheral vascular disease.
People with diabetes are twice as likely to require a hospital
admission compared with the general population. At any one
time, at least 1 in 10 people in hospital has diabetes.17
Actions for Commissioning Teams
Avoiding ADRs: antidiabetic drugs
Insulin and insulin secretagogues (sulfonylureas and
meglitinides) may cause hypoglycaemia.18
Estimated cost of hospital admission for severe hypoglycaemia
is approximately £1,000.18
Factors that increase the risk of hypoglycaemia include18:
o inappropriately high doses of insulin or insulin secretagogue.
o forgotten or delayed meals, or insufficient carbohydrate intake
(especially if taking rapid-acting insulins or insulin
o excessive alcohol intake (or drinking alcohol without food).
o more physical activity than usual.
Actions for Commissioning Teams
Avoiding ADRs: antidiabetic drugs
Prescribers and pharmacists should discuss and reinforce
information on hypoglycaemia.18 Ensure patient:
o is aware of situations that increase risk of hypoglycaemia.
o Is encouraged to eat regularly and include a portion of starchy
carbohydrate with each meal.
o is able to recognise early symptoms and how to treat promptly.
o checks correct insulin has been dispensed.
o always has treatment for hypoglycaemia readily available (e.g. at
home, in the car, pocket or handbag).
o carries identification to alert others (e.g. identity bracelet or card).
If a patient has previously experienced hypoglycaemia
requiring medical attention, refer to a specialist diabetes
Actions for Commissioning Teams
Avoiding ADRs: antidiabetic drugs
Sulfonylurea-induced hypoglycaemia is uncommon and
usually indicates excessive dosage.20
o Glibenclamide is associated with a higher risk of hypoglycaemia
than other sulphonylureas.
o Hypoglycaemia risk should be discussed with patients especially
when concomitant glucose-lowering drugs are used.
Insulin treatment is an important cause of hospital admissions,
mainly as a consequence of severe hypoglycaemia.
o Insulin errors (wrong insulin product, wrong insulin dose, omitted
or delayed insulin dose) account for 60% of insulin-related
adverse events reported in the UK.21
o A review of the National Reporting and Learning System (NRLS)
for the period 1 November 2003 to 1 November 2009 identified
16,600 incidents relating to insulin including six deaths and 12
resulting in severe harm.21
Actions for Commissioning Teams
Avoiding ADRs: antidiabetic drugs
NPSA recommendations for the safer use of insulin include21,22:
o Insulin doses must be measured and administered using an
insulin syringe or commercial insulin pen device.
o Intravenous syringes must never be used for measuring or
administering insulin.
o The term ‘units’ should be used in all contexts. Never use
abbreviations such as ‘U’ or ‘IU’.
o Adult patients on insulin should receive a patient information
booklet and Insulin Passport.
o When prescriptions of insulin are prescribed, dispensed or
administered cross-reference available information to confirm
correct identity of insulin products.
Actions for Commissioning Teams
A note about falls
Falls are a major cause of disability and mortality in older
A meta-analysis (2009) of observational studies found that in
people older than 60 years, falls may be associated with the
use of some medications including:23
other sedatives and hypnotics
Actions for Commissioning Teams
A note about falls
NICE recommend that older people should be asked routinely
whether they have fallen in the last year.24
Patients reporting a fall or considered at risk of falling should
be considered for an individual multifactorial intervention
strength and balance training
home hazard assessment and intervention
vision assessment and referral
medication review with modification or withdrawal
Actions for Commissioning Teams
Systematic review of UK observational studies found 6.5 to
7.5% of hospital admissions related to medication.
Class of drugs most commonly involved include: NSAIDs, low
dose aspirin, warfarin and diuretics.
Good prescribing practice and safe repeat prescribing systems
can reduce risk of ADR related admissions.
Actions for Commissioning Teams
1) Garfield S, Barber N, Walley P et al. Quality of medication use in primary care--mapping the problem,
working to a solution: a systematic review of the literature. BMC Med 2009;7:50.
2) Leendertse AJ, Egberts AC, Stoker LJ et al. Frequency of and risk factors for preventable medicationrelated hospital admissions in the Netherlands. Arch Intern Med 2008;168:1890-6.
3) Howard RL, Avery AJ, Slavenburg S et al. Which drugs cause preventable admissions to hospital? A
systematic review. Br J Clin Pharmacol 2007;63:136-47.
4) Purmohamed, M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital:
prospective analysis of 18.820 patients. BMJ. 2004; 329: 15-19
5) Avery AJ. Top tips for GPs. Strategies for safer prescribing. National Prescribing Centre. 2011.
http://www.npc.co.uk/evidence/resources/10_top_tips_for_gps.pdf <accessed 2/2012>
6) Cardiovascular safety of Cox-2 inhibitors and non-selective NSAIDs. Medicines and Healthcare products
Regulatory Agency. 2010.
http://www.mhra.gov.uk/Safetyinformation/Generalsafetyinformationandadvice/Productspecificinformationandadvice/Product-specificinformationandadvice-A-F/CardiovascularsafetyofCOX2inhibitorsandnon-selectiveNSAIDs/ <accessed 1/2012>
7) Non-steroidal anti-inflammatory drugs. Chapter 10. Section 10.1.1. British National Formulary 2011. 62nd
edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.
8) Low back pain: Early management of persistent non-specific low back pain. CG88. 2009. National Institute
for Health and Clinical Excellence. http://publications.nice.org.uk/low-back-pain-cg88
9) Osteoarthritis: The care and management of osteoarthritis in adults. CG59. 2008. National Institute for
Health and Clinical Excellence. http://publications.nice.org.uk/osteoarthritis-cg59
10) Rheumatoid arthritis: The management of rheumatoid arthritis in adults. CG79. National Institute for
Health and Clinical Excellence. 2009. http://publications.nice.org.uk/rheumatoid-arthritis-cg79
11) Etoricoxib: new prescribing guidelines. Drug Safety Update July 2008; Vol 1, Issue 12: 10
12. Diuretics Chapter 2. Section 2.2 British National Formulary 2011. 62 nd edn. London: British Medical
Association and Royal Pharmaceutical Society of Great Britain.
13) Antiplatelet drugs Chapter 2. Section 2.9 British National Formulary 2011. 62 nd edn. London: British
Medical Association and Royal Pharmaceutical Society of Great Britain.
Actions for Commissioning Teams
References (continued)
14) Aspirin: not licensed for primary prevention of thrombotic vascular disease. MHRA. Drug Safety Update.
October 2009. Volume 3, Issue 3:10
15) Clopidogrel and proton pump inhibitors: interaction-updated advice. Drug Safety Update. Volume 3. Issue
9. Medicines and Healthcare products Regulatory Agency. 2010.
http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087711 <accessed 2/2012>
16) National Patient Safety Agency. Actions that can make anticoagulant therapy safer. Patient Safety Alert.
No. 18. 2007 http://www.nrls.npsa.nhs.uk/resources/?EntryId45=59814
17) Diabetes in the UK 2010: Key statistics in diabetes.
http://www.diabetes.org.uk/Documents/Reports/Diabetes_in_the_UK_2010.pdf Diabetes UK.
18. Recognition, treatment and prevention of hypoglycaemia in the community. NHS diabetes. 2012.
ypoglycaemia_in_the_community <accessed 2/2012>
19) Diabetes in adults quality standard. National Institute for Health and Clinical Excellence. 2011.
20) Endocrine system. Chapter 6. British National Formulary 2011. 62nd edn. London: British Medical
Association and Royal Pharmaceutical Society of Great Britain.
21) The adult patient's passport to safer use of insulin. Patient Safety Alert. National Patient Safety Agency.
2011. http://www.npsa.nhs.uk/corporate/news/passport-to-safer-use-of-insulin/?locale=en
22) New insulin safety guidance issued to reduce wrong dosages. National Patient Safety Agency (NPSA).
2010. http://www.npsa.nhs.uk/corporate/news/the-national-patient-safety-agency-npsa-has-today-issuedguidance-for-all-nhs-organisations-across-england-and-wales-aimed-at-re/ <accessed 2/2012>
23) Woolcott JC, Richardson KJ, Wiens MO et al. Meta-analysis of the Impact of 9 Medication Classes on
Falls in Elderly Persons. Arch Intern Med 2009;169:1952-60
24) Falls:the assessment and prevention of falls in older people. CG21. National Institute for Health and
Clinical Excellence. 2004. http://www.nice.org.uk/nicemedia/live/10956/29582/29582.pdf <accessed 2/2012>

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