Publications
Revised: 13 June 2013
Non-Selective NSAIDS - Cardiovascular, Skin and Gastrointestinal Risks
Website: May 2008
Prescriber Update 2008;29(1):15-16
Medsafe Editorial Team
The safety of non-selective non-steroidal anti-inflammatory drugs (non-selective NSAIDs) has been
evaluated by the Medicines Adverse Reactions Committee (MARC). Non-selective NSAIDs do not
differentiate between COX-1 and COX-2 in their inhibitory action, and are a separate class of drug to
the COX-2 inhibitors. As part of their evaluation, the MARC reviewed adverse reaction reports
received by the Centre for Adverse Reactions Monitoring (CARM) and the WHO (Vigibase), together with
recently published literature and international regulatory activity.
Based on this review, the data sheets for all non-selective NSAIDs approved in New Zealand have been
updated to include warnings about cardiovascular, skin and gastrointestinal risks, and to be consistent
with revisions to the prescribing information in other countries.
Summary of changes to the NSAID data sheets
- After assessing the risk-benefit ratio in each individual patient, the lowest effective dose of
an NSAID should be used for the shortest possible duration.
- Non-selective NSAIDs are associated with an increased risk of serious cardiovascular events,
including cardiac failure, myocardial infarction and stroke, which may increase with dose or
duration of use
- Non-selective NSAIDs may lead to the onset of new hypertension or worsening of
pre-existing hypertension. Patients taking anti-hypertensives with NSAIDs may have an impaired
anti-hypertensive response. Blood pressure should be monitored closely during initiation of
non-selective NSAID treatment and at regular intervals thereafter.
- Fluid retention and oedema have been observed in some patients taking NSAIDs; therefore, caution
is advised in patients with fluid retention or heart failure.
- Non-selective NSAIDs can rarely cause serious, potentially fatal, gastrointestinal effects
such as ulcers, bleeding and perforation, of which the risk may increase with dose or duration of
use. These gastrointestinal effects can occur at any time without warning. If gastrointestinal
bleeding or ulcers occur, NSAID treatment should be stopped immediately.
- The concurrent use of aspirin and non-selective NSAIDs increases the risk of serious
gastrointestinal adverse events.
- Non-selective NSAIDs may rarely cause serious adverse skin events such as exfoliative
dermatitis, toxic epidermal necrolysis and Stevens-Johnson syndrome, which can be fatal and occur
without warning. These severe skin reactions are idiosyncratic and independent of dose or duration
of use.
- Prescribers should warn patients about the signs and symptoms of serious gastrointestinal
toxicity and skin reactions.
General advice on prescribing non-selective NSAIDs
- Use the lowest possible dose and regularly review the need for long-term treatment.
- Consider the potential harms and benefits of non-selective NSAIDs, taking into account
individual patient profiles, particularly risk factors for gastrointestinal, cardiovascular and skin
adverse reactions.
- Advise patients of the risks of harm with non-selective NSAID use, and the warning signs of
serious adverse reactions, so that patients and prescribers can collaboratively manage the risks
associated with non-selective NSAID use.
PIROXICAM – restricted range of indications
Prescribers are reminded of the following recent changes regarding the use of piroxicam.
These restrictions are to manage the greater risks of gastrointestinal side effects and serious skin
reactions associated with piroxicam compared to other non-selective NSAIDs.
- Piroxicam is no longer indicated for acute gout, primary dysmenorrhea, post-operative pain,
acute musculoskeletal disorders, or acute post-traumatic disorders.
- Piroxicam should only be used as second-line treatment for the symptomatic relief of pain
and inflammation in patients suffering from osteoarthritis, rheumatoid arthritis, or ankylosing
spondylitis.
- Piroxicam should only be prescribed by doctors with experience in the diagnostic evaluation
and treatment of osteoarthritis, rheumatoid arthritis or ankylosing spondylitis.
- The first prescription of piroxicam should be for two weeks only, to ensure that the patient
is reviewed before further piroxicam is prescribed.
- Piroxicam is contraindicated in patients with a history of gastrointestinal disorders
associated with bleeding, and those who have had skin reactions to other medicines.
- The dose of piroxicam should be limited to a maximum of 20mg per day and should be regularly
reviewed.
- Piroxicam should always be used at the lowest effective dose (no more than 20mg per day) for
the shortest possible duration.
- Combination therapy with gastro-protective agents should be carefully considered for all
patients, particularly the elderly.
- Piroxicam should not be prescribed in combination with any other NSAID or anti-coagulant.
The data sheets for piroxicam products available in New Zealand have been updated to reflect
these restrictions.
