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 The reviewers for this organization analyze all available evidence, published and unpublished, and provide their assessment of various treatments.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) side-effects and downsides
July 5, 2009 | Leave a Comment
NSAID Nastiness
The biggest recognized drawback to NSAIDs has always been their tendency to cause digestive tract distress. That’s because of how they work in the body. These drugs block the manufacture of a class of chemicals called prostaglandins. These hormonelike compounds have a profound impact on cells throughout the body.
f you sprain your ankle, have a tooth extracted, or develop arthritis, you will experience pain, redness, warmth, and inflammation. This is in large measure due to prostaglandins made by a protein called cyclooxygenase-2 (COX-2). Blocking their formation with NSAIDs like ibuprofen or naproxen means there is less inflammation and pain.
But some prostaglandins made by another protein, COX-1, are beneficial. They protect the stomach lining from damage. If you disrupt their production by blocking COX-1 with NSAIDs, many people complain of symptoms such as nausea, indigestion, abdominal pain, constipation, and diarrhea. It is estimated that more than half of the people taking NSAIDs experience unpleasant gastrointestinal (GI) symptoms.68
Far more worrisome are ulcers, which can bleed or, in the worst case, perforate. A bleeding ulcer or a hole in the stomach wall can very quickly turn into a life-threatening crisis. All too often there are no early warning symptoms that someone is on the verge of disaster.
Although it is hard to know exactly how many people are affected each year, experts estimate that more than 100,000 are hospitalized because of complications caused by NSAIDs and more than 16,000 die.’ The researchers admit these numbers are probably conservative.
Although most physicians have known for a long time that NSAIDs can be hard on the stomach, they didn’t realize that the same drugs can be disastrous for the small intestine. That’s because until recently the small intestine could not be examined directly. Now a small video camera the size of a capsule can be swallowed and the image it transmits can be monitored on a television as the capsule passes into the small intestine.
“If deaths from gastrointestinal toxic effects of NSAIDs were tabulated separately in the National Vital Statistics reports, these effects would constitute the 15th most common cause of death in the United States. Yet these toxic effects remain largely a ’silent epidemic,’ with many physicians and most patients unaware of the magnitude of the problem. 70 Furthermore, the mortality statistics do not include deaths ascribed to the use of over-the-counter NSAIDs “7l
—Michael M. Wolfe et al., The New England Journal of Medicine, 1999
Investigators discovered in a preliminary study that 71 percent of the patients taking NSAIDs had erosions or ulcers in their small intestine, compared to only 10 percent of those not taking these drugs.72 This unexpected finding suggests that NSAID damage to the intestinal tract is even more common and serious than previously suspected.
Frequently, aspirin is sold with an enteric coating that protects the stomach from harm. The coating is designed to dissolve in the small intestine instead, releasing the aspirin there. When we asked gastroenterologist Waqar Qureshi, MD, chief of endoscopy at Baylor University and the Michael E. DeBakey Veterans Affairs Medical Center in Houston, about such formulations, he said, “Enteric-coated drugs might, in fact, cause more damage than regular medications.”" This is because the damage occurs in the small intestine, where the tissue is less resistant to irritating chemicals than the stomach is and where the damage may go undetected.
The COX-2 Catastrophe
With such GI toxicity associated with_ NSAIDs, it’s hardly any wonder that doctors and patients were excited to learn about COX-2 inhibitors. Vioxx, Bextra, and Celebrex were introduced with the idea that they would be gentler on the stomach than other NSAIDs. That’s because these newfangled members of the class were supposed to be “selective.” They would block only the COX-2 enzyme, relieving inflammation as well as aspirin or other NSAIDs do. By sparing the COX-1 enzyme, prostaglandins would be created to protect the stomach from irritation. The promise: pain relief with much less risk of digestive upset or stomach ulcers.
As soon as COX-2 inhibitors were introduced in 1999, they took off like rocket ships. Aggressive advertising directed at consumers and enthusiastic prescribing by physicians turned Celebrex and Vioxx into overnight sensations. Tens of millions of people started popping these pills in the hope that they would relieve pain without the usual problems.
There was just one big oops. By selectively blocking the COX-2 enzyme to relieve inflammation, a crucial prostaglandin called prostacyclin was also reduced. This compound is our friend. It dilates blood vessels and keeps the sticky part of blood, called platelets, from clumping together to form clots. Without adequate amounts of prostacyclin circulating throughout the body, there is an increased risk of blood clots that can trigger heart attacks and strokes.
Early in the development of COX-2 inhibitors some researchers worried that there could be cardiovascular dangers. In 2000, a large Vioxx study suggested that the pain reliever could cause an increased risk of heart attacks and other vascular complications. 74
Neither the FDA nor the manufacturer acted on those early warning flags. In one of the darkest hours in the history of American medicine, millions were allowed to continue taking COX-2 inhibitors until the fall of 2004. By then the handwriting was on the wall. First Vioxx and then Bextra were pulled off the market. In the interim, it is estimated that more than 100,000 people who had been taking COX-2 inhibitors suffered heart attacks and strokes.75 According to FDA safety officer David Graham, MD, as many as 40,000 people may have died .71
The Broken Promise
If COX-2 inhibitors like Vioxx, Bextra, and Celebrex had truly protected the digestive tract from damage, it might have been easier to justify their approval, aggressive marketing tactics, and high prices. But an editorial in the Journal of the American Medical Association described the science behind COX-2 inhibitors as a “house of cards” based on wishful thinking. They were marketed “with unrealistic expectations about pain relief, marked gastrointestinal protection, and safety.”77
Canadian researchers tracked hospital admissions caused by gastrointestinal bleeding before and after the introduction of COX-2 inhibitors (Vioxx, Celebrex, and Mobic). Instead of dropping when the new drugs became available, as investigators had expected, the rate of hemorrhage and hospitalization for older people paradoxically rose by 10 percent .78 British researchers asked a similar question: Would COX-2 inhibitors be easier on the stomach than traditional NSAIDs? The an-
FDA NSAID WARNING
“NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, m ocardial infarction [heart attack], and stroke, which can be fatal.-71 rt
—FDA Public Health Advisory, April 7, 2005
saver: There was no evidence to suggest that the newer drugs were less harmful to the digestive tract.” In hindsight, it looks as if we were all sold an expensive bill of goods.
Other NSAID Troubles
No sooner did the FDA wake up to the risk of heart attacks and strokes associated with COX-2 inhibitors than the agency had to deal with the possibility that other NSAIDs might pose a similar problem. Decades after these drugs began to be marketed, the FDA reviewed the data and decided that all such prescription pain relievers should carry a stronger black-box warning.
The FDA goes on to warn that people with risk factors for cardiovascular disease are especially vulnerable to these life-threatening problems. That includes almost everyone with arthritis. If you accumulate enough birthdays to develop osteoarthritis, you are bound to have some hardening of the ar-
OTHER NSAID ADVERSE EFFECTS
• High blood pressure
• Fluid retention, edema
• Congestive heart failure
• Stomach ulcer (bleeding)
• Perforation of the stomach
• Perforation of the small intestine
• Perforation of the large intestine
• Kidney damage
• Severe allergic reaction
• Skin rash (toxic)
• Itching
• Stevens-Johnson syndrome
• Liver damage
• Blood disorders (anemia)
• Asthma worsening
teries. But that’s not all. The FDA has gone on to emphasize other problems with NSAIDs as well.
It is easy for your eyes to glaze over when looking at such a list. You may also assume that some of these potential side effects are rare events, but that could be a dangerous assumption. A study of older and potentially sicker patients revealed a startling incidence of kidney damage associated with Celebrex. More than 20 percent of the people taking this COX-2 inhibitor experienced kidney toxicity (fluid retention, high blood pressure, and kidney failure).81 If patients had some kidney impairment before the study started (a common situation in older people), the likelihood of kidney toxicity jumped to more than 50 percent! We assume other NSAIDs are likely to have a similar effect on kidney function.
NSAID Survival Strategy
By now it should be clear that nonsteroidal anti-inflammatory drugs, including the COX-2 inhibitors, can be trouble with a capital T! They aren’t all that effective for arthritis, especially of the knee. Some NSAIDs may actually contribute to joint deterioration if they are taken for years. Then there’s the risk of serious side effects like bleeding ulcers, hypertension, heart
Aspirin
Aspirin prevents blood clots and lowers the risk of heart attacks and strokes. Unlike other NSAlDsJt does not raise blood pressure.
Aspirin remains the best buy for pain relief. At pennies a day, it reduces the inflammation that is at the root of so many chronic ailments, including arthritis, diabetes, and Alzheimer’s disease. Regular aspirin users seem to develop fewer cancers of the colon, rectum, prostate, pancreas, ovary, skin, lung, and breast.
Downside: Damage to the stomach lining. The potential for indigestion, gastritis, and ulcers makes this drug inappropriate for many. Bleeding or perforated ulcers can be life threatening. Anyone on long-term aspirin therapy must be under medical supervision.
Cost: Approximately $2 to 5 per month
ASPIRIN AND BAKING SODA
Although it will not be identical to Alka-Seltzer, you can create your own buffered, soluble aspirin. In a glass, combine:
• 2 uncoated aspirins
• 8 ounces club soda or sparkling water
•’/p teaspoon baking soda
• Juice from 1/4 wedge lemon
Wait till the aspirins dissolve and then drink. This formula is not appropriate for people on a sodium-restricted diet.
attacks, strokes, and kidney or liver damage. Why would anyone in his or her right mind take such medicine?
The most obvious answer is that there aren’t very many pharmaceutical alternatives. Doctors have relatively little to offer beyond NSAIDs when it comes to pain and inflammation. And sometimes you hurt so much that you need something to help you move your bones around. When used in the short-term and with appropriate safeguards, it may be possible to take an NSAID. But which one should you consider?
Aspirin remains our first choice by far. No other NSAID or OTC pain reliever has ever been proven more effective. In addition, aspirin reduces the risk of heart attacks and thrombotic (clotting) strokes. As a bonus, there is growing evidence that aspirin may diminish the likelihood of developing many common cancers. We discourage the use of enteric-coated aspirin because this merely moves the aspirin to the small intestine, where it can do serious damage.
Our preferred method for taking aspirin is as a liquid. In Europe, Australia, Canada, New Zealand, and dozens of other countries you can find several soluble, effervescent aspirin products. Brands like Aspro and Disprin are very popular because all you do is drop the aspirin tablets into a glass of water, where they fizzle and dissolve within seconds. This makes them a little faster acting and possibly a little less irritating to the stomach (though there is no guarantee of protection).
Soluble aspirin never really caught on in the United States, except in the form of Alka-Seltzer. It is a combination of as-pirin, sodium bicarbonate, and citric acid advertised for relief of “acid indigestion, sour stomach, heartburn with headache, body aches and pains.” The trouble with Alka-Seltzer is that it’s way more expensive than plain aspirin and there’s too much sodium for folks who have congestive heart failure or salt-sensitive hypertension.
If you would prefer not to pay an arm and a leg for fizzy aspirin, you could make your own soluble aspirin for a fraction of the cost. All you have to do is buy some club soda or sparkling water. Drop two regular-strength aspirin tablets in the fizzy water and let them dissolve. It will take a couple of minutes.