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Topical NSAIDs

I have a mental basket of drugs that I suspect may be placebos. In that basket were the topical versions of non-steroidal anti-inflammatory drugs (NSAIDs). When the first products were commercially marketed over a decade ago, I found the clinical evidence unconvincing, and I suspected that the modestly positive effects were probably due to simply rubbing the affected area, or possibly due to the effects of the cream or vehicle itself. Frankly, I didn’t think these products worked. So when I recently noticed a topical NSAID appear for sale as an over-the-counter treatment for muscle aches and pains (seemingly only in Canada, for now), I was confident it would make a good case study in bad science.

It’s not that I’m partial to the oral NSAIDs. Yes, they’re among the most versatile, and probably most well-loved drugs in our modern medicine cabinet. They offer good pain control, reduce inflammation and can eliminate fever. We start using it in our sick and feverish infants, through childhood and adulthood for the aches and pains of modern life, and into our later years for the treatment of degenerative disease like osteoarthritis, which affects pretty much everyone as we age. An astonishing 17 million Americans use NSAIDs on a daily basis, and this number is expected to grow as the population ages. In the running groups I frequent, ibuprofen has the affectionate nickname “Vitamin I”, where it’s perceived as an essential ingredient for dealing with the consequences of training.

But NSAIDs have a long list of side effects. Not only do they cause stomach ulcers and bleeding by damaging the gastrointestinal mucosa, there are heart risks, too. It was the arrival (and departure) of the drugs Bextra and Vioxx that led to documentation of the potential for cardiovascular toxicity. And now there’s data to suggest that these effects are not limited to the “COX-2″ drugs – almost all NSAIDs, including the old standbys we have used for years, seem capable of raising the risks of heart attacks and strokes.

So despite my initial skepticism, I took another look at the topical NSAIDs. The data were not what I expected.

The use of NSAIDs

ASA (acetylsalicylic acid, Aspirin) the prototypical NSAID, traces its origin back to willow bark, a natural source of salicylate. All NSAIDs work the same way, interrupting the production of inflammatory and pain-related hormones called prostaglandins. Since ASA’s introduction in 1897, more than two dozen chemically related drugs have come to market. They’re now among the commonly used drugs used worldwide, playing a crucial role in pain management. Given the ubiquity of acute pain conditions, as well as chronic conditions like osteoarthritis, it’s estimated that 1 in 20 physician visits are related to prescriptions for NSAIDs. In general, all NSAIDS have equivalent efficacy at the population level, though individual response, and side effects, can vary between drugs. The discovery of different forms of cyclooxygenase enzymes led to new drugs that targeted COX-2 (at sites of inflammation) rather than COX-1 (which is involved with the stomach mucosa. Inhibit COX-2 rather than COX-1, the thinking went, and you could get the antinflammatory action of a traditional NSAID without the gastrointestinal toxicity. However, as the COX-2 saga demonstrated, effects can include the creation of a significant prothrombic effect – with devastating consequences.

The Risks of NSAIDs

Prescription drugs can and do cause significant morbidity, leading to frequent hospital admissions. While we may think nothing of popping a few ibuprofen now and then, NSAIDs have been linked to about 30% of drug-related hospital admissions, and it’s estimated that 12,000-16,000 Americans die annually as a result of gastrointestinal bleeding caused by NSAIDs.

Stomach bleeding and ulcers are a consequence of an NSAID’s mechanism of action – their effect on prostaglandins. The lining of the gut is weakened, and stomach and duodenal ulcers result. Even very low doses of ASA have been documented to have measurable effects on the mucosal lining of the gastrointestinal tract. The risks of gastrointestinal toxicity are significantly increased in the elderly, in those on high doses of NSAIDs, and when combined with other drugs (e.g., steroids) that suppress normal stomach protection.

The cardiovascular risks of NSAIDs became well documented following the worldwide withdrawal of rofecoxib (Vioxx) and international examinations of the cardiovascular risks of the entire category of drugs. Data have now emerged to convincingly establish that most NSAIDs (except ASA) are associated with an increased risk of cardiovascular events. Chronic (routine) consumption of most drugs is linked to small but real increases in heart attacks and stroke. These effects may be a consequence of interference with the beneficial effects of ASA (Aspirin), direct negative cardiovascular effects, and exacerbations of fluid balance, leading to heart failure.

When it comes to cardiovascular risks, not all NSAIDs are the same. A recently published network meta-analysis summarizes the differences, and the overall risks. Both traditional NSAIDs, like naproxen, ibuprofen, and diclofenac, as well as the COX-2 selective NSAIDs, like celecoxib (Celebrex) and rofecoxib (Vioxx) were studied. Happily for those that use over-the-counter anti-inflammatories only occasionally: naproxen seems to be the safest among the NSAIDs, with little to no increase in risk, and ibuprofen’s elevated risk seems limited to regular doses of 1200mg per day or more. So for the individual consumer, when do the risks outweigh the benefits of NSAIDs? Ultimately this comes down to an individual consideration of reasons for use, risk factors, and expected benefits.

To be clear, the absolute cardiovascular risks of NSAIDs, on an individual level, are low, compared to the other side effects of NSAIDs. They seem to cause three or more excessive events like heart attacks and stroke events, per 1000 patients, per year. Compare this to the 20-40 per 1000 per year that may have a (sometimes fatal) stomach bleed, a risk that’s 4x that of non-users. Still, their risk profile suggests that a consideration of their risk and benefits is warranted, particularly when they’re being contemplated in people with preexisting cardiovascular disease. On balance, when treating short-term conditions, the incremental risk in patients without cardiovascular disease is probably very low. Still, it seems prudent to use safer alternatives first (when possible) and if using NSAIDs, considering the lowest possible dose for the shortest possible duration.

Topical NSAIDs: The evidence

Over the past two decades, evidence has emerged to demonstrate that topical versions of NSAIDs are well absorbed through the skin and reach therapeutic levels in synovial fluid; muscle, and fascia. With topical use, little drug actually circulates in the plasma, leading to levels that are a fraction of comparable oral doses. As adverse events from NSAIDs are largely dose-related, it’s expected (thought not as well documented) that serious side effects should be minimized.

For chronic conditions like osteoarthritis, the data are of fair quality and are persuasive. The National Institutes for Health and Clinical Excellence osteoarthritis guidelines provides a nice summary of the trials. Studies varied by site of osteoarthritis (knee, hand, hip, etc), the type of NSAID studied, the regimen, and trial design. On balance, there’s good evidence to show that topical NSAIDs are clinically- and cost-effective for short term (< 4 weeks) use, especially when pain is localized. Topical and oral versions seem to be similarly effective under these circumstances, and there there’s a significant reduction in non-serious adverse events with topical products. While there’s no conclusive evidence to demonstrate a reduction of serious adverse events, they’re expected to be better than oral products, given the blood levels are much lower. What impressed me is that topical NSAIDs are recommended as a preferred treatment before oral NSAIDs. And given many taking oral NSAIDs need to take stomach protecting drugs like omeprazole, the topical products, while more expensive than their oral versions, may actually be more cost-effective overall.

A Cochrane review from 2010 is equally positive about the treatment of acute pain conditions. Forty-seven trials were included in their analysis that considered topical NSAIDs for strains, sprains, and overuse-type injuries. Compared to placebo, topical NSAIDs were evaluated to be effective, with few side effects, with a number needed to treat (NNT) of 4.5. About 6 or 7 out of 10 users can expect to achieve pain control with a topical NSAID, compared to 4 with a placebo. Side effects are comparable to placebo. And given systemic absorption is lower, the serious toxicity we associate with NSAIDs should be lessened, too. Not bad.

Given there’s no long-term data with topical NSAIDs, the evidence doesn’t give us enough insight to understand the risk profile beyond a few weeks. Consequently it seems reasonable to try using topical products instead of oral products, particularly for intermittent, rather than chronic, pain conditions. While compounding pharmacies have made topical versions of NSAIDs for years, there’s little information on effectiveness and safety of these products. As commercial formulations are supported with pharmacokinetic and clinical studies demonstrating efficacy, they are the preparations of choice.

Conclusion

NSAIDs, which already had a bad side effect profile, cause more harm then we thought. Evidence has emerged to demonstrate that topical NSAIDs are effective for many conditions that might otherwise require oral therapies. There’s little evidence to demonstrate that topical NSAIDs are effective for some types of pain, like back pain, headache, or neuropathic pain. But based on what’s now known about the cardiovascular toxicity of NSAIDs, it’s likely that topical products provide a superior risk/benefit perspective for regular and occasional users. The Cochrane review points out that topical NSAIDs are widely accepted in some parts of the world, but not in others. The reasons why are not clear. But having read the evidence, I’ve changed my opinion. And when I’m recovering from my next marathon, I’ll think about reaching for a topical NSAID, instead of that comforting bottle of vitamin I.

References

Haroutiunian, S., Drennan, D., & Lipman, A. (2010). Topical NSAID Therapy for Musculoskeletal Pain Pain Medicine, 11 (4), 535-549 DOI: 10.1111/j.1526-4637.2010.00809.x

Massey T, Derry S, Moore RA, & McQuay HJ (2010). Topical NSAIDs for acute pain in adults. Cochrane database of systematic reviews (Online) (6) PMID: 20556778

Solomon DH. Up-to-Date: Nonselective NSAIDs: Overview of adverse effects; Nonselective NSAIDs: Overview of adverse effects. From Up-To-Date (Database on the Internet).

Trelle, S., Reichenbach, S., Wandel, S., Hildebrand, P., Tschannen, B., Villiger, P., Egger, M., & Juni, P. (2011). Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis BMJ, 342 (jan11 1) DOI: 10.1136/bmj.c7086


Posted in: Pharmaceuticals, Science and Medicine

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43 thoughts on “Topical NSAIDs

  1. weing says:

    It looks like you can’t win with these drugs. Check out the study showing protection against Parkinson’s by ibuprofen.

    http://www.neurology.org/content/early/2011/03/01/WNL.0b013e31820f2d79.abstract?sid=99d3c198-7908-4214-8469-156af92c47fc

  2. Scott says:

    It’s always good to see an honest account of “I thought X. Then I looked at the evidence more carefully. The evidence changed my conclusion.” That’s what makes medicine science-based.

  3. tuck says:

    Great post.

  4. Thanks for the flexible mind, Scott. I was also skeptical at first, and then persuaded by the evidence when I published on this topic about a year ago.

    But here’s some interesting skeptical caveats for you: the evidence may show that topical NSAIDs work for pain caused by inflammation … but many of the pains that people think are caused by inflammation are actually not. There is extensive evidence that repetitive strain injuries are not inflammatory in nature, but degenerative, what I call tissue “rot” — a failure of tissue repair and maintenance processes to keep up with stress and load. (Discussed in detail in a long repetitive strain injury article on SaveYourself.ca.) So it’s not clear that topical NSAIDs will work for RSI, which is probably the single most common presumed indication.

    It will probably also fail with garden variety muscle aching, which is far more common a problem than most professionals or patients realize, and often accounts for sharper, more burning pain than people expect from muscle — the kind of pain they might think is “inflamed.”

    And there’s more.

    As you refer to in your conclusion, it’s common practice for runners and other athletes to take ibuprofen to cope with delayed onset (post-exercise) muscle soreness. However, there is good evidence that this is ineffective — perhaps because DOMS is also not actually an inflammatory condition, or minimally inflamed. I wrote about the “vitamin I” problem recently.

    So that’s a lot of pain for which these products might not be indicated!

  5. moderation says:

    Great summary … a useful reference for patients, family and friends.

  6. Scott says:

    @ Paul:

    That actually raises a very interesting question. Most laypeople don’t really have any clear conception that some pain is inflammatory vs. not (I certainly had never thought about it before). Usually they seem to be viewed as generic pain relievers. If that’s not an accurate view of where they are effective, then that would present a problem.

  7. chaos4zap says:

    Now, if we could convince the folks over at “head-on, apply directly to your forehead” to add NSAID’s to their formula, then their claims would at least be somewhat plausible. Cheap Formula with nothing it that doesn’t work and people buy anyway, or using active ingredient that actually could work but will reduce your profit margin? On second thought…..they aren’t changing anything.

  8. Scott, I definitely do think it presents an awkward problem, and of course we just don’t have the experimental data we need to take a clear position for public education. Unfortunately, topical NSAIDs will have to be tested much more thoroughly before we will really know exactly what they do and do not work for. There are many causes of pain — it can’t work for all them! It’s relatively obvious that Voltaren gel is not going to help neuropathic pain, or visceral pain, etc. Unfortunately, there are quite a few less obvious differences between pain causes.

    So all that can really be said with confidence at this point is that not all pain is inflammatory and although topical NSAIDs almost certainly do work on pain of inflammatory nature — and that’s certainly a good thing, because lots of pain is certainly caused by inflammation — your mileage is very likely to vary widely depending on exactly what you’re treating.

  9. Joe says:

    Aspirin does not trace back to willow bark. The name is derived from Acetylated SPIRsaure IN. Spirsaure was (is?) the German name for salicylic acid as it was first found (on the continent) by deriving an extract containing salicylic aldehyde from the genus Spiraea (meadowsweet, not willow); which was oxidized to provide the acid. The suffix ‘in’ was just a popular ending for a drug.

    The salicylic acid produced from the meadowsweet extract was found to have analgesic properties; but it was too harsh on the stomach. Aspirin was tried as stomach-friendly derivative ca. 1897.

    The main analgesic in willow is salicin, which is a glycoside of glucose and salicylic alcohol. In the late 20th century, it was found that salicin is digested to those components, absorbed, and the alcohol is metabolized to the acid. There is also salicylic acid in willow bark; hence the name derived from the genus Salix. Aspirin is far cheaper to produce than salicin. I don’t know if they have significantly different pharmacological profiles.

    Most of the literature supporting this is in old literature (much of it in German, I speak German like I was in America born) but the naming of aspirin is described in a book “Aspirin” by Diarmuid Jeffreys (Bloomsbury, 2005). Although his narrative demonstrates that willow was not involved in the development of aspirin, he starts with willow as if it mattered.

    (I find it curious that scientists were committed to finding the active ingredients of natural products (and their derivatives) 200 years ago; yet, today, there is still a strong push to use pills made from shrubbery.)

  10. Th1Th2 says:

    Joe,

    “Aspirin does not trace back to willow bark.”

    I thought what he stated was clear enough to understand —”ASA (acetylsalicylic acid, Aspirin) the prototypical NSAID, traces its origin back to willow bark, a natural source of salicylate.”

  11. Jan Willem Nienhuys says:

    The information of Joe is more or less correct. The German Wikipedia says about the same: http://de.wikipedia.org/wiki/Salicyls%C3%A4ure. Salicylic acid was originally obtained by oxidation from salicin (from willows). The article http://en.wikipedia.org/wiki/History_of_aspirin derives a lot of information from Jeffreys. The structure of salicylic acid (from willows) and Spirsäure (from meadowsweet) was found independently in 1838, and afterwards seen to be identical. I think that when Bayer started making Aspirin, neither willows nor meadowsweet were the source of salicylic acid anymore, but phenol from coal tar.

  12. chaos4zap says:

    I don’t find it curious that society in general is digressing with respect to medicine; I find it annoying and a rather overt sign that people are far more susceptible to marketing that reason and logic. 200 years ago, they didn’t have a choice. Chewing on tree bark and roots wasn’t working too well, so they had to progress. Those progresses have immensely increased our life expectancy and overall quality of life, so much so, that most are ignorant of how we got here. It’s kind of similar to the anti-vaccine crowd. Not all that long ago conditions like Malaria, Flu, Polo, etc… were devastating to populations (as they still are in undeveloped countries now) so we used science and came up with a solution. Now that those diseases are less prevalent, it’s easy for the Oprah watchers of the word to say we don’t need the shots anymore. And they can actually say this with a straight face. Maybe the answer is to let them have their tree bark, roots and homeopathy……natural selection will take over, thin out the herd and maybe one day we can finally get back on track.

  13. Th1Th2 says:

    “1828 – Johann Büchner of Munich isolates pure salicin from willow bark. Salicin is the compound in willow bark that relieves pain. The name salicin was derived from salix, which is the Latin word for willow tree.

    1835 – Karl Lowig makes salicylic acid from meadowsweet flowers.

    1838 – Raffaele Piria converts salicin into salicylic acid. This is the first time salicylic acid is obtained from willow bark in the laboratory.”

    Of course, ancient people (~1500 BC) have been using salicylic acid obtained from natural sources (willow, myrtle, birch meadowsweet etc) to relieve pain. They just don’t have the “laboratory” to synthesize one.

  14. Th1Th2 says:

    chaos4zap,

    “It’s kind of similar to the anti-vaccine crowd. Not all that long ago conditions like Malaria, Flu, Polo, etc… were devastating to populations (as they still are in undeveloped countries now) so we used science and came up with a solution.?

    What’s the difference between a poliovirus-contaminated fecal matter and an OPV on top of a sugar cube comfortably given to a child? Nothing.

  15. antipodean says:

    Bravo!

  16. chaos4zap says:

    Th1Th2,

    Are you trying to make the point that contaminated fecal matter would make a sufficient vaccine?

  17. Th1Th2 says:

    chaos4zap,

    It could be anything for as long as it is sufficient enough to deliver the poliovirus. Since children love sweets and gullible enough to take it, science once again has found a solution.

  18. Chris says:

    The person who goes by Th1Th2 is not known for being rational. Ignore it:

    Why should I let the child walk on the dirt when there is a dry concrete pavement next to it? A toddler would readily know which is the safe path to take even without the knowledge of C. tetani, but I am just fascinated how parents are offering very poor choices (or lack thereof).

  19. khan says:

    So what do I do for chronic pain?

    Aspirin Aleve Ibuprofin?

    Do I go to a doctor and become a ‘drug seeker’?

  20. rwk says:

    According to Chris
    The person who goes by Th1Th2 is not known for being rational. Ignore it:

    The person who goes by Joe is not known for being rational either:

    (I find it curious that scientists were committed to finding the active ingredients of natural products (and their derivatives) 200 years ago; yet, today, there is still a strong push to use pills made from shrubbery.)

    The new drug, formally acetylsalicylic acid, was named Aspirin by Bayer AG after the old botanical NAME for meadowsweet, Spiraea ulmaria.

  21. Hmmm, did someone change the spam filters or are the spammers just getting smarter.

  22. SnottyProfessor says:

    Thank you very much for the post. I have been a sufferer of upper-back pain for a some time and here in Turkey, topical NSAIDs along with a topical muscle relaxer (Thiocolchicoside) is usually two of the first things the doctors prescribe along with physical therapy. It seems to help.

    I do have a question about the headaches and systemic NSAIDs, though. Why do NSAIDs relieve most headaches (including migraines)? Are some headaches inflammatory in nature? If that is the case, why aren’t corticosteroids ever used to treat headaches?

  23. Bogeymama says:

    Physicians in our neck of the woods very commonly prescribe diclofenac in strengths ranging from 4-10%. Virtually every pharmacy compounds it. A Pennsaid rep told me years ago that her sales in our area were significantly lower than the rest of the country because of our preference for the cheaper gel version made by pharmacies. Since there has never been a rep promoting the gel, it must be meeting the needs of patients or it wouldn’t be continuing to grow in usage. Indeed, patients seem to report a high level of satisfaction and pain relief. I recently damaged my ligaments in a ski injury, and opted for the 10% gel to treat my swelling and pain rather than oral NSAIDS.

    The quality of the gel varies between pharmacies, due to different techniques (the higher strengths can get very runny, particularly when cold). It would be very interesting to see an actual study done on these products, as they are relatively inexpensive and easy to use.

  24. kirkmc says:

    Hmm, I find this article interesting. I’ve lived in France for more than 15 years, and topical NSAIDs have been available here for at least 20 years if not more (I never needed them before that). Since I can’t take NSAIDs, they are the only thing I can use for inflammation-based pain from arthritis (other than codeine, which works for the pain, though not the inflammation). There doesn’t seem to be any doubt here about their effectiveness, though, naturally, not every one works for each person and for all types of pain. I currently use diclofenac, and sometimes ketaprofen, and both work fine, but for different types of pain.

    But you say:

    “There’s little evidence to demonstrate that topical NSAIDs are effective for some types of pain, like back pain, headache, or neuropathic pain.”

    Does that mean that NSAID’s work for neuropathic pain? I never thought that was the case. And as for topical NSAIDs working for headaches, well, I think that’s kind of obvious. :-)

  25. Scott says:

    Since there has never been a rep promoting the gel, it must be meeting the needs of patients or it wouldn’t be continuing to grow in usage.

    Doesn’t follow – this is a pure ad populum. See homeopathy, for instance.

  26. Scott – I see your point – But I do think it’s a stretch to suggest that homeopathy hasn’t been promoted. :)

  27. chaos4zap says:

    Th1Th2,

    it’s true that anything contaminated with polio would introduce polio to a child, but you’re missing the point. Long before the smallpox vaccine was created, people were taking puss and scabs from sores and grinding it up and blowing it into each other’s noses and mouths. This did, indeed, sometimes have the desired effect of people getting just a little bit sick and then have immunity. The flip side is that some people just got full blown small pox. There can be a fine line between the dose/response necessary to provoke anti-body development and the dose/response that just gives the person the full blown condition you are seeking to prevent. Studies are conducted to determine where this fine line is. Simply giving a child something contaminated with an unknown strain of whatever disease, in an unknown concentration….is not at all comparable to the research that goes into vaccines for mass production.

  28. Joe says:

    @Jan Willem Nienhuys on 03 Mar 2011 at 4:07 pm

    Of course, you are right. However, my understanding of the history is that the salicylic acid (SA) derived from salicin was not used for analgesia. The SA derived from meadowsweet was so used, and was the inspiration for the development of aspirin. After the natural source of SA, derived from meadowsweet, was found effective, I believe the cheaper, synthetic SA was substituted. Thus, the original source of SA as an analgesic was meadowsweet.

    It is a fine distinction; but I bred body lice in the 1970s and so I am a professional nitpicker.

    If I am wrong, it won’t be the first time.

  29. Scott says:

    @ michele:

    I also think it’s a stretch to say that the diclofenac hasn’t been promoted either. For example, by the pharmacists who want to make money compounding it. Or by the people who have concluded on insufficient evidence that it works. Pharma reps aren’t the only people who push such things.

    So the situations of homeopathy and diclofenac gel are not distinguishable from the evidence provided.

  30. Scott – fair enough, then. I had never heard of diclofenac, so I had assumed it wasn’t promoted. But I can see how it might be promoted locally by a pharmacist.

    And I do see your point that popularity does not prove that a substance works. But I do not mind the short cut in reasoning that says if multiple people report the same kind of benefit from using a medication and the mechanism for working is plausible, it is worth researching. Maybe more so, if those people haven’t been given a placebo boost with a positive marketing message. On the other hand, the research indicates “not better than placebo” results, I do not think it is worth researching again, and again and again.

    I often use the inverse of this reason. If I know that a product is highly promoted for a common problem (such as particular wrinkle cream) and yet I do not see a large number people benefiting from that product (look, people still have wrinkles), I am skeptical of the real benefit of that product.

  31. Scott says:

    “Worth researching” I’ll certainly buy. I just object to “must be meeting the needs of patients.”

  32. Bogeymama says:

    “For example, by the pharmacists who want to make money compounding it.”

    Don’t think so. Diclo gel is so ubiquitous, every pharmacy compounds it. The profit is no greater for that than any prescription, and it takes more time to do, and most pharmacies are racing against the clock all day. There’s no money in it for the pharmacy. Also, promotion of pharmacy services is actually against regulations (in Canada), so a pharmacist caught doing it would get into trouble. ALSO, most pharmacists are staff pharmacists, and get paid by the hour. There’s no motivation there. It really does seem to be driven by word-of-mouth … from patients who have tried it back to the doctors who prescribe it and causing a ripple effect.

    I will concede that some promotion is happening now from the Voltaren OTC reps, but it has come way too late in the game. The OTC gel is slightly higher than 1%, so the docs are more inclined to prescribe a higher strength anyways, just like they’ve been doing for 10+ years. Plus, thanks to sites such as this one and nofreelunch, most doctors don’t see reps anymore – at least in this area.

    Boiron, however, has a very active sales force, calling on pharmacies, naturopaths, homeopaths … anyone who will listen to them. I’ve actually been detailed (or should I say “ambushed”) by a Boiron rep.

  33. Interesting, Bogeymama. Can you clarify: so Voltaren is a milder packaged version of something that doctors have always been able to prescribe and have a pharmacist prepare for the patient? And a stronger one, at that?

    Did not know that.

  34. Bogeymama says:

    That’s right – the Voltaren gel that is available OTC (came out late 2009??) is 1.16% of diclofenac diethylamine – equivalent to 1% diclofenac sodium. I admit, it’s a lovely gel, much better than anything I’ve seen compounded. Most pharmacies keep a compounded stock of 5% and 10% gels of diclofenac sodium and dilute with 0% to make up other prescribed strengths.

    My discussion with the Pennsaid rep (diclofenac drops) was in the early 2000′s (at a playgroup for our babies!), and she expressed her frustration back then that there was virtually no market for her product due to the high uptake of compounded diclofenac gel by physicians in her territory. Other parts of Canada were not using the gel as much according to her.

    I began practising here in Alberta in the mid-late 1990′s and saw it prescribed sporadically, but then I stopped for a while to have babies … once I started back into it, the diclo gel was already being used widely. Patients report positive experiences, but I think physicians are happier to prescribe it to lessen side effects of NSAIDS. Some even prescribe a mixture of diclofenac and cyclobenzaprine.

  35. cloudskimmer says:

    Is there any topical preparation available now, over the counter, in the United States, or do we have to travel to Canada or Europe to find it? –or get a prescription from a Doctor? Must it be made by a pharmacist? Could a do-it-yourselfer grind up some ibuprofen in a mortar and mix it with massage cream and get the same effect?
    If diclofenac has been implicated in liver damage, is it safe to take as a topical medication?
    Chronic pain sufferers are warned not to use pain medications for long periods of time, but there seems to be no alternative. Since blood levels are lower with topical preparations than with oral medications, it seems like the creams would be safer.

  36. Toiletman says:

    Aspirin has its name from an old name for meadowsweet (spiraea), a plant that also contains salicyl.

    I never understood why North America withdrew metamizole from the market since its side-effects, while potentially threatening, are not any worse than those of NSAIDS. But anyways, I think the best way to treat chronic pain (I also suffer from it) are first trying antidepressants like duloxetine and amitriptyline and if those do not work, one would need to go to weak opioids. I’m not sure if there is any extended release version of codeine but I know that tramadol is available this way. Since it’s not only based on opioid properties, it might be the best choice. There is, of course, the problem of dependence but I remember (but am not completely sure of it) that people with chronic pain who got opioids and sticked to the time- schedule to take it were not very likely to have this problem but still, it is possible, especially if you also have a history of mental problems.
    Two other european pain killers are flupirtin and nefopam but I could not find much about them and their safety.

  37. weing says:

    I think metamizole was pulled from the market because of reported cases of agranulocytosis. Too bad. It is the most powerful non-narcotic analgesic that I know of from personal experience.

  38. pmoran says:

    http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040168

    Steven Goodman herein points to flaws in the work leading to Ionnadis’ unfortunate generalization that “most published research findings are wrong.”

  39. overshoot says:

    When the first products were commercially marketed over a decade ago

    Assuming you’re not counting topical saliclyates, which have been available at least since the 50s and IIRC much longer.

  40. TsuDhoNimh says:

    topical versions of non-steroidal anti-inflammatory drugs (NSAIDs). When the first products were commercially marketed over a decade ago Make that 100 years ago.

    Oil of Wintergreen (methyl salicylate) is listed in a 1918 book of pharmacology as being used topically for arthritis and muscle strains.

    Ben-Gay ointment’s formula dates to the 1890s (methyl salicylate and menthol)

  41. Artour says:

    Chronic inflammation has its origins in cell hypoxia which is an integral part of the inflamed tissue microenvironment. Hypoxia remains the key factor in cancer, heart disease and many other conditions. Why do modern people suffer from tissue hypoxia?
    Cell hypoxia is a normal outcome of chronic hyperventilation. But people with normal breathing are as rare these days as people with smallpox. Hyperventilation is present in more than 90% of modern normals.http://www.normalbreathing.com/i-hyperventilation.php and even more common in the sick.

    Regardless of ventilation-perfusion ratio or problems with lungs, alveolar hypocapnia always leads to cell hypoxia. Or, in simple terms, heavy breathing results in less oxygen in cells and HIF-1 (hypoxia-inducible factor 1) over-expression.

    “Interestingly, increasing evidence accumulated over recent years suggests an additional important regulatory role for HIFs in inflammation”
    (from Imtiyaz HZ, Simon MC. Hypoxia-inducible factors as essential regulators of inflammation, Curr Top Microbiol Immunol. 2010;345:105-20.)
    More facts:
    http://www.normalbreathing.com/co2-inflammatory-response.php

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