Jul
5
Topical NSAIDs
Americans have been deprived of an arthritis treatment that is widely available all over the world. Topical NSAIDs (gels, creams, and sprays) are very popular with patients and physicians in Europe, Australia, Canada, New Zealand, and dozens of other countries, but they are virtually ignored in the United States. The very same drugs (diclofenac, ibuprofen, ketoprofen, ketorolac, piroxicam, etc.) that cause so much mischief
PPI CAUTION
“Although there seems to be a general agreement among gastroenterologists that proton pump inhibitors should be prescribed to high-risk patients taking low-dose aspirin, 91 such a strategy has not been widely adopted because of a lack of definitive evidence to support it.”92
—Carlo Patrono et al., The New England Journal of Medicine, 2005
when taken orally can be applied to the skin with little, if any, risk of stomach ulcers, kidney problems, heart attacks, strokes, or other systemic complications. Except for aspirin-like compounds (salicylates) found in OTC products like Aspercreme, BenGay, Myoflex creme, and Sportscreme, you will not find topical NSAIDs on pharmacy shelves in the United States. That’s because the FDA has never approved these formulations for topical use.
How effective are topical NSAIDs for relieving the pain and inflammation of arthritis? Over the years there have been dozens of clinical trials of such products for both temporary (acute) discomfort and longer-term (chronic) treatment. 3 One review of 26 double-blind, placebo-controlled trials involving 2,853 patients concluded that “topical NSAIDs were effective and safe in treating acute painful conditions for 1 week.”94
Okay, okay! We hear you: “One week, big deal.” Another review examined 14 double-blind, placebo-controlled trials including almost 1,500 patients. The conclusion: “Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for 2 weeks.”" That’s a little better, but still not a long-term solution. One sour note comes from the thorough and objective Cochrane Library. The reviewers for this organization analyze all available evidence, published and unpublished, and provide their assessment of various treatments. This 2004 review looked at studies of use of topical NSAIDs for longer than 2 weeks and determined that “after 2 weeks there was no evidence of efficacy superior to placebo. No trial data support the long-term use of topical NSAIDs in osteoarthritis.”96
Based on this summary we would be inclined to suggest that topical NSAIDs be used for 2 weeks or less to relieve an acute arthritis flare-up. On the brighter side, there are now four newer clinical trials of use for 3 to 12 weeks. 97,98 Investigators specifically looked at osteoarthritis of the knee. In each study, diclofenac (Pennsaid or Voltaren Emugel) was superior to placebo in providing relief, with only “minor local irritation and no significant systemic adverse events.”99, 100 In a 12-week head-to-head comparison of oral diclofenac with topical diclofenac (Pennsaid Lotion), their effectiveness was comparable. But side effects like nausea, indigestion, stomach pain, and liver damage were much more likely to occur with the oral NSAID.101
Pennsaid Lotion is interesting because the formulation relies on DMSO (dimethyl sulfoxide) to help get the drug through the skin and into the area of the joint where pain relief is desired. DMSO is a solvent that is uniquely able to penetrate the skin and carry medications with it. We have long wondered why drug companies were not using DMSO to facilitate absorption. Now the makers of Pennsaid have done just that.
So, how can you get topical NSAIDs? If you were in Australia you could purchase products like piroxicam (Feldene Gel), ibuprofen (Nurofen Gel), ketoprofen (Orudis Gel), and diclofenac (Voltaren Emulgel) over the counter without a prescription. At this time that is impossible in the United States. Nevertheless, it is possible to purchase oral ibuprofen and ketoprofen over the counter. That means a compounding pharmacist (one who mixes raw ingredients into finished products) can legally purchase ibuprofen or ketoprofen powder, make a cream or a gel,
sell
and it to you without a prescription.
An alternative would be to shop online for one of the brands mentioned above. Since they are nonprescription in many countries, you may be able to purchase them and not have US Customs give you any problems. One final option, and our number one recommendation, is to have a US physician write a prescription for Pennsaid. This topical form of diclofenac has been tested in several clinical trials and found to produce long-lasting relief from osteoarthritis. You would then need to contact a Canadian pharmacy online or by phone to have the prescription filled. Since this drug is not available.
**** Pennsaid Lotion (diclotenat)
This topical NSAID has been shown to provide lasting relief from the pain and inflammation of osteoarthritis. It may produce some skin irritation, but does not appear to cause significant systemic toxicity, as oral diclofenac does.
Side effects: Skin dryness, flakiness, and rash
Downside: Not available in the United States. Available by prescription in Canada, Finland, Iceland, Italy, Greece, Portugal, the United Kingdom, and elsewhere.
Cost: Approximately $60 to $120 per month
Jul
5
Aspirin-Like Drugs for Arthritis Treatment
July 5, 2009 | Leave a Comment
Aspirin-Like Drugs
One of the best arthritis buys in the pharmacy is a frequently overlooked prescription drug called salsalate. It has been around for so long that many physicians have forgotten about it. Because salsalate is available generically, the cost should only be the amount of your co-pay. Even without insurance, the cost shouldn’t be much more than $1 a day.
salsalate is a kissing cousin to aspirin (it is salicylsalicylic acid instead of acetylsalicylic acid). Because it lacks the acetyl group, salsalate behaves differently in the body. Studies done 20 to 30 years ago suggest that it may be a little less irritating to the stomach than aspirin because it is absorbed only from the small intestine. (There are no data on whether it irritates the small intestine the way enteric-coated aspirin does.)
salsalate is just as effective as aspirin at relieving joint pain or morning stiffness. Unfortunately, it probably won’t prevent blood clots or heart attacks the way aspirin does. salsalate may also be a little more likely to cause dizziness or ringing in the ears. It does require medical supervision, just as any NSAID does, and probably has similar side effects.
Another aspirin-like arthritis medicine that is often over-
BRANDS OF SALSALATE
• Amigesic • Mono-Gesic
• Artha-G • Salflex
• Disalcid • Salsitab
looked is choline magnesium trisalicylate (Tricosal, Trilasate, Trisalicylate). It too requires a prescription and should cost a lot less than $1 a day. Like salsalate, it may be a little less irritating to the stomach than aspirin. Again, it provides no extra protection against heart attacks or strokes.
ibuprofen and Naproxen
For those who cannot tolerate aspirin or who want a traditional NSAID to get them over a hump, which drugs would we consider using? This is an incredibly difficult call because of the new and alarming data linking these drugs to heart attacks. If forced to recommend something, we would probably fall back on naproxen. For one thing, it is a good deal. When prescribed generically the co-pay should be $10 or less a month. Even when purchased over the counter the cost should be no more than 15 cents per day. That compares to as much as $4 to $7 a day for Celebrex.
One study found that ibuprofen and naproxen are not associated with accelerated progression of hip and knee arthritis the way some other NSAIDs are.82 Another possible plus with these two drugs may be a somewhat safer cardiovascular profile. One epidemiological study demonstrated no increased risk of heart attacks or other cardiovascular complications with these two pain relievers when they were used for short periods of time. 13 Another study, unfortunately, found that
N a p r o x e
Naproxen is an NSAID available both OTC and by prescription (Anaprox, Naprelan, Naprosyn). it does a reasonable job of relieving arthritis pain and the effect lasts a little longer than that of Ibuprofen. Some researchers believe that it may be less likely to pose cardiovascular risks than other NSAIDs. This is unconfirmed, and naproxen may not be as safe as we would wish.84
Downside: Damage to the stomach lining. Indigestion, gastritis, and ulcers. High blood pressure, kidney problems, liver complications, rash, constipation, diarrhea, dizziness, and ringing in the ears.
Cost: Approximately $4 to $5 per month SIGNS OF TROUBLE!*
• Chest pain
• Shortness of breath or sudden weakness
• Slurred speech or paralysis
• Severe stomach pain or indigestion
• Black, tarry stools
• Sudden weight gain
• Trouble removing a ring
• Skin rash, itching, blisters, fever
• Nausea, fatigue, yellow eyes, flu symptoms
*If any of these symptoms occur, contact your physician immediately or visit urgent care.
NSAIDs like ibuprofen increase the risk of a second heart attack.” A Danish study of nearly 60,000 heart attack survivors showed that NSAIDs such as Celebrex, ibuprofen, and diclofenac were linked to an increased risk of heart attack death. This complication showed up within several weeks of starting on the pain reliever. The researchers concluded that heart attack survivors need to be very cautious about the kind of pain reliever they use.
Even people who have not had a heart attack need to be wary about NSAIDs. Anyone with high blood pressure, high cholesterol, blockage in a coronary artery, or kidney problems is likely to be at increased risk of a heart attack when taking such pain relievers. 86
Finnish investigators studied more than 33,000 heart attack patients hospitalized between 2000 and 2003. By comparing them to 139,000 control subjects, the researchers found that taking any NSAID increased the chance of a heart attack by approximately 40 percent. 87
For those who think taking aspirin together with a drug like Advil or Aleve might diminish any risk of a blood clot, think again. There are no clear-cut data to support that notion. There is even some worry that drugs like ibuprofen and naproxen might undo the cardiovascular protective benefits of aspirin.88,89 Be wary of interactions with other medications, especially blood pressure drugs (ACE inhibitors), furosemide (Lasix), lithium (Eskalith, Cibalith, Lithane, Lithobid, Lithotabs), methotrexate, (Rheumatrex, Trexal), and blood thinners like warfarin (Coumadin).
Of course anyone who opts to use an NSAID must treat these drugs with the respect they deserve. Treatment for more than 10 days requires medical supervision and great vigilance. Remember, there may be an increased risk for heart attack, hypertension, heart failure, kidney problems, and ulcers.
To counteract the risk of serious GI toxicity, many gastroenterologists now routinely recommend acid-suppressing drugs called PPIs (proton pump inhibitors) in combination with NSAIDs. Medications such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex) are supposed to diminish the likelihood of NSAID-induced stomach upset and ulcers.’ Despite this belief, there is no guarantee that such drugs can prevent all ulcers or perforations. A review of the use of low-dose aspirin in the New England Journal of Medicine cautions against any sense of complacency. This should apply to all NSAIDs.
Jul
5
NSAIDs (nonsteroidal anti-inflammatory drugs)
July 5, 2009 | Leave a Comment
NSAIDs
After the roller-coaster ride with cortisone, you would think that the medical establishment would have been more careful about the next big thing. Maybe doctors were so anxious to find something safer for arthritis that they didn’t appreciate that they might be jumping from the frying pan into the fire.
Aspirin was the first nonsteroidal anti-inflammatory drug (NSAID). It was introduced in 1899 and was a mainstay of arthritis treatment for most of a century. Aspirin works a little differently from other drugs in this class and has advantages that make it unique. For almost 100 years aspirin was the Rodney Dangerfield of the drugstore. It got relatively little respect. Because aspirin was available over the counter, it took physicians a long time to appreciate how valuable it could be against heart attacks, strokes, and even cancer. Because it has been around for so many years, doctors have often assumed that newer medicines would provide better pain relief. And they (and their patients) have often been disappointed.
The launch of prescription indomethacin (Indocin) in 1965 really put NSAIDs on the map. These drugs became some of the most successful pharmaceuticals of their time. Whenever a new anti-inflammatory drug came along, it generated tremen-
NON-ASPIRIN NSAIDS
• Celecoxib (Celebrex)
• Diclofenac (Cataflam, Voltaren)
• Etodolac (Lodine)
• Fenoprofen (Nalfon)
• Flurbiprofen (Ansaid)
• Ibuprofen (Advil, Motrin, etc.)
• Indomethacin (Indocin)
• Ketoprofen (Orudis, Oruvail)
• Ketorolac (Toradol)
• Meloxicam (Mobic)
• Nabumetone (Relafen)
• Naproxen (Aleve, Anaprox, Naprosyn)
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Sulindac (Clinoril►
• Tolmetin (Tolectin)
dons excitement. Drugs like sulindac (Clinoril), piroxicam (Feldene), ibuprofen (Motrin), and naproxen (Naprosyn) had their time in the limelight. Then along would come something newer and doctors would switch their allegiance.
Those of us who have observed this game of medicinal musical chairs for more than 40 years have become somewhat cynical about this class of pain relievers. The fickle switching from one drug to another suggests to us that no particular NSAID really stands out. There have not been really great head-to-head clinical trials that prove one drug is superior to another or significantly safer than others in the class.
If truth be told, these drugs really don’t work all that well when it comes to relieving the pain and inflammation of arthritis, especially of the knee. Despite the fact that tens of millions of people have spent countless billions of dollars on these medications, there are surprisingly few data demonstrating long-term benefit with their use. A scientific analysis of 23 different studies was published in the British Medical Journal in 2004. This meta-analysis involved more than 10,000 patients and revealed a shocking discovery: “NSAIDs can reduce short-term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support prolonged use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended.”‘
What a bombshell! This review of the world’s medical literature on NSAIDs concluded that such drugs are reasonable only for short-term use. But arthritis is a long-term affair. The only conclusion we can draw: Regular use of such drugs is inappropriate for a chronic condition like arthritis.
Even more alarming, some evidence suggests that these medications may actually be harmful to arthritic joints. 61,62,63 Researchers in the Netherlands followed more than 1,600 patients for several years. Patients who had been taking the NSAID diclofenac (Arthrotec, Cataflam, Voltaren) experienced greater joint deterioration as determined by x-ray evidence. The authors concluded, “Our data suggest that diclofenac may not be harmless and may induce accelerated progression of hip and knee OA [osteoarthritis].”64
OTC Mistake?
When NSAIDs like ibuprofen (Advil, Cap-Profen, Excedrin 113, Genpril, Haltran, lbuprin, Ibuprohm, Ibu-Tab, Medipren, “OTC analgesics including NSAIDs are widely used, are frequently taken inappropriately and potentially dangerously, and users are generally unaware of the potential for adverse side effects. -,65
—C. Mel Wilcox et al., Journal of Rhouniatology, 2005
Midol IB, Motrin IB, Nuprin, Pamprin IB, Profen, etc.) and naproxen (Aleve) were approved for over-the-counter (OTC) sale, millions of people were delighted to have access to these powerful anti-inflammatory drugs. An Rx-to-OTC switch was a radical concept back in 1984. Even though the FDA assured consumers that such drugs were so safe that they did not require medical supervision, many physicians opposed the plan. They feared that side effects such as rash, fluid retention, high blood pressure, gastritis, and ulcers might make these drugs too dangerous for casual use. The FDA ignored the worriers.
Dear reader, we cannot tell you whether the decision to make NSAIDs available OTC was a blessing or a curse. The FDA has been incredibly inept at keeping track of adverse reactions to prescription medications. The agency’s track record on nonprescription pills is even worse. So, we really do not know how many ulcers, heart attacks, or other serious complications have occurred because of easy access to NSAIDs.
What we do know is that people are gobbling down these drugs almost like candy. Based on scientific surveys (Roper and the National Consumers League), it is estimated that 23 million Americans use a nonprescription NSAID (ibuprofen or naproxen) every day.” Only about one in five consumers bothers to read the directions on the label and fewer than one in three checks out dosing instructions. Perhaps that’s why one-fourth of them take more than the recommended dose. Scarier still, roughly half of the people surveyed were unaware of the potential for NSAID toxicity or just plain didn’t care.