E-drug: Association Diclofenac/Misoprostol (cont)
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In regard to misoprostol use, the benefit/risk is as follows - at least
based on the only trial that I am aware of - Ann Int Med 1995; 123:214-9
In patients (mean age 68) receiving NSAIDs for RA for 6 months misoprostol
at a dose of 250 micg QID reduced the chance of serious gastrointestinal by
0.38% (placebo group 0.95% versus 0.57% in the misoprostol group) or in
other words you would have to treat 263 patients with misoprostol for 6
months to prevent one event. There was no difference in deaths, GI
obstructions or perforations. I am unaware of any evidence that misoprostol
reduces the reflux or stomach queasiness that some (approx 10-15%)
patients get from NSIADs. In fact, there was an INCREASE (approx 7%)
in adverse GI events in the misoprostol group, primarily diarrhea and
cramping and 5% of the patients had to discontinue the drug due to
adverse effects.
It has been my experience - a level 5 evidence based statement - that once
presented with these results clinicians and patients don't even consider
trying this agent.
Some suggestions to potentially decrease the chance of problems with NSAIDs:
1) promote the use of acetaminophen/paracetamol over the NSAIDs -
many people respond well to acetaminophen or can cut back on the dose
of the NSAID by adding in some acetaminophen
2) if patients require NSAIDs for pain control let the patient find the
lowest effective dose - some patients do well taking these agents once a day
or even once every couple of days - the suggestion that NSAIDs need to be
taken two or three times daily is not based, as far as I know, on
pharmacodynamic studies but rather pharmacokinetic studies. Talk to patients
who run out of their prescription for an NSAID and many will tell you it
takes 2-3 days for their pain and stiffness to return. I always tell
patients that the correct dose for an NSAID is between the maximum
recommended dose and zero mg and there is nothing about the patient (size,
sex, degree of pain) that helps one predict the correct dose. Anyone who has
been started on the typical doses of an NSAID and who gets a positive
response should be then told to titrate the dose back to find the "correct"
dose for them. I have seen a number of patients who take an NSAID
once every 2-3 days and get a good response.
3) Inform the patient about the potential for GI complications and what they
should do if they occur - although I realise that 25% of GI bleeds are
asymptomatic - only 16% of patients who developed a GI bleed on NSAIDs
report being informed of this adverse effects and 4% are informed
about what to do if adverse symptoms occur. 36% of patients with GI
bleeds due to
NSAIDs had epigastric pain before the bleed and all but 2 of these patients
continued taking the drug (Br J Clin Pharmacol 1996;42:253-6).
Hope the above helps.
James McCormack, Pharm.D.
Associate Professor
Faculty of Pharmaceutical Sciences
University of British Columbia
Vancouver, B.C.
Canada
604 822-1710
jmccorma@interchange.ubc.ca
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