The Lupus Book: A Guide for Patients and Their Families, Third Edition (39 page)

medication. Of the many drug therapies for lupus, and among the most pre-

scribed and accepted are what doctors call ‘‘the anti-inflammatories.’’ These

remedies include
aspirin products
and other
nonsteroidal anti-inflammatory
drugs
, or NSAIDs. A survey has documented that at any given time, 80 percent of all SLE patients are taking one of these agents on a regular or intermittent basis. This chapter will endeavor to help lupus patients negotiate the tricky ins and outs of NSAIDs in an effort to maximize potential benefits while minimizing toxicity.

ASPIRIN AND ITS FIRST COUSINS ONCE REMOVED

The fever-lowering property of willow bark (
Salix alba
) was known to the ancients and used by Hippocrates, Galen, and Pliny. The active salicylate ingre-

dient was isolated in France in 1827, and acetylsalicylic acid (aspirin) specifically identified in 1899 in Germany. When Dr. Marian Ropes founded the first

lupus clinic in Boston in 1932, aspirin was the only real medication she had to work with. For reasons that are still unclear, only one well-designed study has ever assessed the efficacy of aspirin in SLE. Fortunately, it was a definitive one.

In 1980, the National Institutes of Health proved beyond the shadow of a doubt

that aspirin was helpful in SLE.

What Does Aspirin Do and Not Do in SLE?

The salicylate class of medicines, of which aspirin is the most important, ame-

liorates lupus by lowering fevers, treating headaches, diminishing joint or muscle aching and inflammation, and decreasing both serositis (pleurisy, pericarditis, peritonitis) and malaise. It has no effect on skin, heart, lung, kidney, liver, central nervous system, or blood involvement of the disease. Salicylates do not

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The Management of Lupus Erythematosus

modify the disease; that is, they do not put lupus into remission and do little about the underlying immune process. Aspirin relieves lupus through the inhibition of prostaglandin, a chemical that promotes inflammation and pain in ar-

thritic disorders.

The Many Faces of Aspirin

Aspirin can be administered in many ways. Along with the tablet form, it is

available as a suppository, a liquid suspension (Arthropan), or a salve (e.g.,

Aspercreme, Ben-Gay). Most people, however, take it orally. Aspirin can be

buffered to diminish stomach irritation (e.g., Bufferin); these preparations work quickly (in 10 to 15 minutes) but are out of the system in 3 to 4 hours. Two

regular or unbuffered aspirins (325 milligrams) are effective in less than an hour and work for 4 to 6 hours. Patients with headaches often benefit when caffeine

is added to aspirin (e.g., Excedrin). The anti-inflammatory dose of aspirin de-

pends on the individual and how that person’s liver and kidney will handle the

drug. An active rheumatoid-like arthritis responds to 325-milligram tablets taken three or four at a time four to five times a day. Since this involves popping a lot of pills, rheumatologists may prescribe high-dose timed-release preparations (e.g., Zorprin), which last 8 to 12 hours and need to be taken only two or three times a day. Salicylate blood levels are monitored in some patients to see if they are taking enough aspirin to enjoy its maximal benefits. Too much aspirin can cause ringing in the ears; an old saw claims that the correct dose of aspirin for rheumatoid-type arthritis is one tablet a day less than what causes the ears to ring.

Low-dose aspirin (baby aspirin, 81 milligrams) may be prophylactic in lupus

patients with antiphospholipid antibodies (Chapter 21). Why low-dose and not

regular aspirin? Low-dose salicylates inhibit a chemical that promotes clotting; regular aspirin also inhibits this chemical but additionally inhibits a second

chemical that counteracts this. Taking 1 grain (81 milligrams) of aspirin daily may decrease the risk of strokes or miscarriages due to the lupus anticoagulant.

Salicylates other than aspirin are slightly modified. Some of these should not

induce bleeding, rarely upset the stomach, and cannot cause ulcers. These pre-

scription sodium or magnesium salicylates (Magan, Salsalate, Trilisate, Disalcid) are excellent anti-inflammatory preparations for patients who have had an ulcer or look bruised all the time. Unfortunately, they are much weaker than regular

aspirin and are often ineffective.

WHAT ARE NSAIDS AND WHY ARE THEY USED IN LUPUS?

Pharmaceutical companies began their search for a better aspirin in the 1940s and in 1952 came up with
butazolidin (Phenylbutazone
). However, this is no longer mar-Taming Inflammation: Anti-inflammatory Therapies

[209]

keted in the United States. It was followed by
indomethacin (Indocin)
in 1965 and
ibuprofen (Motrin)
in 1974. Since then, numerous additional preparations have been introduced: they are listed in Table 26.1 and discussed below. All of these preparations are more potent than aspirin, so that fewer pills are required to achieve the same effect. However, very few of these drugs are superior to aspirin: most have more side effects and are all more expensive.

All the NSAIDs, including aspirin, function similarly; their most important

effect is inhibiting prostaglandin. But very few drug trials using these agents in SLE have been published. The manufacturers of NSAIDs have been careful not

to promote the use of these drugs in SLE, since this would be ill advised if the disease should affect the kidney or liver. (That is a possibility in up to half of all patients.) In fact, no NSAIDs are FDA-approved for use in SLE. In spite of

this, as noted, 80 percent of all lupus patients take NSAIDs on a regular or

intermittent basis. Some patients take NSAIDs on a daily, regular basis while

others only use them when they have pain or inflammation. The reasons for this

Table 26.1.
Major Nonsteroidal

Anti-inflammatory Drugs (NSAIDs)

Salicylates

Aspirin

Sodium salicylates (Trilisate, Salsalate, Disalcid)

Diflusinal (Dolobid)

Magnesium salicylate (Magan, Doan’s)

Proprionic acid derivatives

Oxaprozin—Daypro

Naproxen—Naprosyn, Anaprox, Aleve

Flurbiprofen—Ansaid

Ibuprofen—Motrin, Advil

Ketoprofen—Orudis, Oruvail

Fenoprofen—Nalfon

Acetic acid derivatives

Sulindac—Clinoril

Diclofenac—Voltaren, Cataflam

Tolmetin—Tolectin

Indomethacin—Indocin

Selective cox-2 antagonists

Celecoxib–Celebrex

Valdecoxib–Bextra

Oxicam derivatives

Piroxicam–Feldene

Meloxicam–Mobic

Others

Etodolac—Lodine

Ketrolac—Toradol

Nabumetone—Relafen

Meclofenamates—Meclomen, Ponstel

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The Management of Lupus Erythematosus

are that the NSAIDs are effective in relieving fevers, headaches, muscle aches, malaise, arthritis, and serositis associated with SLE. All NSAIDs have widely

varying pain-relieving properties.

Which NSAID Should Be Used?

The ideal NSAID is inexpensive, safe, and effective; however, none of them fits this billing exactly. Below, we examine each NSAID and explain the pros and cons for using each.
Flurbiprofen (Ansaid)
may uniquely counteract osteoporosis and mineralize bone. It is of moderate potency and rarely induces changes in the patient’s mental status.
Naproxen (Naprosyn)
is the best-selling NSAID in the United States.

Taken twice a day and available as a liquid suspension, it is highly potent, but the possibility of gastritis requires careful monitoring. A salt of naproxen called
Anaprox (available over the counter as Aleve)
takes 15 minutes to work (as opposed to 2 hours for naproxen) and is used as an analgesic for headaches or menstrual

cramps, for example.
Oxaprozin (Daypro)
is a highly effective once-a-day ‘‘timed-release Naprosyn.’’ Doses of these drugs should be decreased in older patients, and they can all be toxic to the stomach. Of all the NSAIDs,
fenoprofen (Nalfon)
causes the most salt retention and is among those that are most toxic to the kidneys. This weak preparation must be taken four times daily and has no place in managing SLE.

Ketoprofen (Orudis)
is a moderately potent preparation used three times a day. Its major advantage is a rapid onset of action (10 minutes) and highly effective analgesic effects. Therefore I prescribe ketoprofen when a quick response is mandated for intermittent pain. It is also available as a 24-hour timed-release preparation
(Oruvail)
.
Ibuprofen (Motrin, Advil, Nuprin, etc.)
has flexibility of dosing (200-, 400-, 600-, and 800-milligram strengths) and is available without a prescription.

This weak agent is taken four times daily if used regularly. (Chapter 9 reviews some of the problems with these drugs, especially the central nervous system reactions observed with ibuprofen.)

Diclofenac (Voltaren)
is the world’s best-selling NSAID for arthritis in general. An extremely effective analgesic of moderate potency, it is coated to protect the stomach and has mild anti-inflammatory properties, as does its close relative
Cataflam
. However, liver function must be monitored every 3 months.
Piroxicam (Feldene)
is a highly potent agent that has the advantage of being taken once a day. But many lupus patients have difficulty tolerating its side effects: it can enhance sun sensitivity. Piroxicam can also be hard on the stomach.

Meloxicam (Mobic)
is similar to piroxicam but may be slightly cox-2 selective (see page 205).
Sulindac (Clinoril), indomethacin (Indocin)
, and
tolmetin (Tolectin)
are associated with a 10 to 15 percent incidence of central nervous system complications (e.g., headache, mental clouding) not observed with any other

NSAIDs. Sulindac is moderately potent, well tolerated, and taken twice a day.

Indomethacin is the strongest NSAID on the market and is also available as a

Taming Inflammation: Anti-inflammatory Therapies

[211]

suppository and as a 24-hour timed-release oral preparation. Intended for shortterm use, it carries the greatest risk of toxicity to the liver, stomach, and kidneys with continuous use. Tolmetin is a moderately potent preparation that infrequently prolongs bleeding times and thus may be used in dialysis patients and

prior to surgery.

Meclofenamate (Meclomen)
is an expensive, weak agent that induces diarrhea in 30 percent of patients but may help psoriasis.
Etodolac (Lodine)
is a mild, very well tolerated NSAID that has an excellent kidney, stomach, and liver

safety profile. The strongest NSAID analgesic preparation is
Ketorolac (Toradol)
, which is available orally or by injection. Approved only for short-term or occasional use, it has minimal anti-inflammatory properties. Finally,
nabumetone
(Relafen)
is a once-a-day medication of moderate potency that causes ulcers less often than any of the preparations mentioned above and has an excellent liver

and kidney safety profile. Some patients report that this agent increases their energy levels.

Why Must We Be Careful When Using NSAIDs?

The NSAIDs can be extremely effective. Their use can mark the difference

between holding a job and being on disability. They can greatly improve one’s

quality of life. However, numerous caveats apply when using these drugs. First

of all,
all patients taking NSAIDs on a daily basis should have complete blood
counts as well as liver and kidney blood chemistries every 3 to 4 months
. An increase in liver enzymes to greater than 2.5 times normal mandates discontinuation of the NSAID so as to protect the body from liver failure. Similarly,

patients with lupus nephritis probably should not take NSAIDs unless it is for

a specific circumstance and under close medical supervision for a limited period (e.g., to treat acute gout or bursitis) and renal function is carefully monitored.

All NSAIDs have the capacity to induce kidney failure. In patients with normal

liver and kidney function, the risk of developing altered function ranges from

0.1 to 10 percent, depending on the agent employed. Fortunately, most patients

have no symptoms, and these abnormalities are almost always reversed when

they stop taking the drug.

Most important, all NSAIDs commonly induce erosions in the stomach, and

this may lead to bleeding ulcers. Nationwide, 3 percent of all patients taking

NSAIDs on a regular basis develop bleeding ulcers. A low hemoglobin or he-

matocrit (part of the complete blood count), black stool, or a positive Hemoccult test (stool smear for blood) are often the first signs of trouble. Tobacco, steroid use, and alcohol abuse increase the risk of ulcers. The use of H blockers (Zan-2

tac, Pepcid, Axid, Tagamet), antacids, or sulcrafate (Carafate) relieves dyspepsia and heartburn associated with NSAIDs (seen in 20 to 30 percent) but do
not

prevent the development of ulcers. I advise patients who need to be on

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The Management of Lupus Erythematosus

NSAIDs and have had gastric erosions or ulcers to add proton-pump inhibitors

(lansoprazole, or Prevacid; omeprazole, or Prilosec, also Nexium, Aciphex, or

Protonix) or misoprostol (Cytotec) to their regimen. These drugs
prevent
ulcers from developing.

Other adverse reactions can result from NSAIDs. These include bloating and

fluid retention, easy bruisability, diarrhea, ringing in the ears, headaches, prov-ocation of allergy or asthma attacks, and rashes. Because NSAIDs prolong

bleeding times, they should be discontinued at least a week before any surgery