Web site: 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 indicationsPrescribers 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.
