Ulcerative Colitis (cont.)
5-ASA Compounds (Azulfidine, Asacol,
Pentasa, Dipentum)
5-ASA (5-aminosalicylic acid), also called mesalamine, is chemically similar
to aspirin. Aspirin (acetylsalicylic acid) has been used for many years in
treating arthritis, bursitis, and tendinitis (conditions of tissue
inflammation). Aspirin, however, is not effective in treating ulcerative
colitis. On the other hand, 5-ASA can be effective in treating ulcerative
colitis if the drug can be delivered directly (topically) onto the inflamed
colon lining. For example, Rowasa enema is a 5-ASA solution that is effective in
treating inflammation in and near the rectum (ulcerative proctitis and
ulcerative proctosigmoiditis). However, the enema solution cannot reach high
enough to treat inflammation in the upper colon. Therefore, for most patients
with ulcerative colitis, 5-ASA must be taken orally. When pure 5-ASA is
taken orally, however, the stomach and upper small intestine absorb most of the drug
before it reaches the colon. Therefore, to be effective as an oral agent for ulcerative colitis, 5-ASA has to be modified chemically to escape
absorption by the stomach and the upper intestines. These modified 5-ASA
compounds are sulfasalazine (Azulfidine),
mesalamine (Pentasa, Rowasa, Asacol), and
olsalazine (Dipentum).
Azulfidine
Sulfasalazine (Azulfidine) has been used successfully for many years in
inducing remission among patients with mild to moderate ulcerative colitis.
Inducing remission means decreasing intestinal inflammation and relieving
symptoms of abdominal pain, diarrhea, and rectal bleeding. Sulfasalazine has also
been used for prolonged periods of time to maintain remissions.
Sulfasalazine consists of
a 5-ASA molecule linked chemically to a sulfapyridine molecule. (Sulfapyridine
is a sulfa antibiotic). Connecting the two molecules together prevents
absorption by the stomach and the upper intestines prior to reaching the colon.
When sulfasalazine reaches the colon, the bacteria in the colon will break the
linkage between the two molecules. After breaking away from 5-ASA, sulfapyridine
is absorbed into the body and then excreted in the urine.
Most of the active 5-ASA drug, however, remains in the colon to treat colitis.
Most of the side
effects of sulfasalazine are due to the sulfapyridine molecule. These side effects
include nausea,
heartburn, headache, anemia, skin rashes, and, in rare instances,
hepatitis and kidney inflammation. In men, sulfasalazine can reduce the sperm
count. The reduction in sperm count is reversible, and the count usually returns to normal after
discontinuing sulfasalazine or by changing to a different 5- ASA compound.
The benefits of sulfasalazine generally are dose related. Therefore, high doses
of sulfasalazine may be necessary to induce remission. Some patients cannot
tolerate high doses because of nausea and stomach upset. To minimize stomach
upset, sulfasalazine generally is taken after or with meals. Some patients find it
easier to take Azulfidine-EN (enteric-coated form of sulfasalazine).
Enteric-coating helps decrease stomach upset. The newer 5-ASA compounds do not
have the sulfapyridine component and have fewer side effects than sulfasalazine.
Asacol
Asacol is a tablet
consisting of the 5-ASA compound, mesalamine, surrounded by an acrylic resin coating.
(Asacol is sulfa free). The resin coating prevents the 5-ASA from being absorbed
as it passes through the stomach and the small intestine. When the tablet
reaches the terminal ileum and the colon, the resin
coating dissolves, thus releasing 5-ASA into the colon.
Asacol is effective in inducing remissions in patients with mild to moderate
ulcerative colitis. It also is effective when used for prolonged periods of time to maintain
remissions. The recommended dose of Asacol to induce remission is two 400-mg
tablets three times daily (total of 2.4 grams a day). Two tablets of Asacol
twice daily (1.6 grams a day) is recommended for maintaining remission.
Occasionally, the maintenance dose is higher.
As with Azulfidine, the benefits of Asacol are dose-related. If patients do not respond to 2.4 grams a day of Asacol, the dose
frequently is increased to 3.6 grams a day (and sometimes even higher) to induce
remission. If patients fail to respond to the higher doses of Asacol, then
alternatives, such as corticosteroids, are considered.
Pentasa
Pentasa is a capsule consisting of the 5-ASA compound mesalamine
inside controlled-release spheres. Like Asacol, it is sulfa free. As the capsule travels
down the intestines, the 5-ASA inside the spheres is slowly released into the
intestines. Unlike Asacol, the mesalamine in Pentasa is released into the
small intestine as well as the colon. Therefore, Pentasa can be effective in
treating inflammation in the small intestine and the colon. Pentasa is currently
the most logical 5-ASA compound for treating mild to moderate Crohn's disease
involving the small intestine. Pentasa also is used to induce remission and
maintain remission among patients with mild to moderate ulcerative
colitis.
Olsalazine (Dipentum)
Olsalazine (Dipentum) consists of two
5-ASA molecules linked together. It is sulfa free. The linked 5-ASA
molecules travel through the stomach and the small intestine unabsorbed. When
the drug reaches the terminal ileum and the colon, the normal bacteria in the intestine break the
linkage and releases the active drug into the colon and the terminal ileum. Olsalazine
has been used in treating ulcerative colitis and in maintaining remissions. A
side effect unique to olsalazine is secretory diarrhea (diarrhea resulting from
excessive production of fluid in the intestines). This condition occurs in 5-10%
of patients, and the diarrhea sometimes can be severe.
Colazal
Colazal (balsalazide) is a capsule in
which the 5-ASA is linked by a chemical bond to another molecule that is inert
(without effect on the intestine) and prevents the 5-ASA from being absorbed.
This drug is able to travel through the intestine unchanged until it reaches the
end of the small bowel (terminal ileum) and colon. There, intestinal bacteria
break apart the 5-ASA and the inert molecule, releasing the 5-ASA. Because
intestinal bacteria are most abundant in the terminal ileum and colon, Colazal
is used to treat inflammation predominantly localized to the colon. Colazal
recently has been approved by the FDA for use in the United States.
More clinical trials are needed to compare the effectiveness of
Colazal to the other mesalamine compounds such as Asacol in treating ulcerative
colitis. Therefore in the United States, choosing which 5-ASA compound has
to be individualized. Some doctors prescribe Colazal for patients who
cannot tolerate or fail to respond to Asacol. Others prescribe Colazal for
patients with predominantly left sided colitis, since some studies seem to
indicate that Colazal is effective in treating left sided colitis.
Side Effects of 5-ASA Compounds
The sulfa-free 5-ASA
compounds have fewer side effects than sulfasalazine and also do not
impair male fertility. In general, they are safe
medications for long-term use and are well-tolerated.
Patients allergic to aspirin should avoid 5-ASA compounds
because they are chemically similar to aspirin.
Rare kidney inflammation has been reported with the use of 5-ASA
compounds. These compounds should be used with caution in patients with known
kidney disease. It also is recommended that blood tests of kidney function be
obtained before starting and periodically during treatment.
Rare instances of acute worsening of diarrhea, cramps, and
abdominal pain may occur which is at times may be accompanied by fever, rash,
and malaise. This reaction is believed to represent an allergy to the 5-ASA
compound.
Rowasa Enema
Rowasa is the 5-ASA compound mesalamine in enema form and is effective in ulcerative
proctitis and ulcerative proctosigmoiditis (two conditions where active 5-ASA
drugs taken as enemas can easily reach the inflamed tissues directly). Each Rowasa enema
contains 4 grams of mesalamine in 60 cc of fluid. The enema usually is administered
at bedtime, and patients are encouraged to retain the enema through the night.
The enema contains sulfite and should not be used by patients with sulfite
allergy. Otherwise, Rowasa enemas are safe and well-tolerated.
Rowasa also comes in suppository form for treating limited proctitis. Each
suppository contains 500 mg of mesalamine and usually is administered twice daily.
While some patients improve within several days of starting Rowasa, the usual
course of treatment is three to six weeks. Some patients may need even longer courses of
treatment for optimal benefit. In patients who do not respond to Rowasa, oral
5-ASA compounds (such as Asacol) can be added. Some studies have
reported increased effectiveness in treating ulcerative proctitis and
proctosigmoiditis by combining oral 5-ASA compounds with Rowasa enemas. Oral 5-ASA
compounds also are used to maintain remission in ulcerative proctitis and
proctosigmoiditis.
Another alternative for patients who fail to respond to
Rowasa or who cannot use Rowasa is cortisone enemas (Cortenema). Cortisone is a
corticosteroid that is a potent anti-inflammatory agent. Oral corticosteroids
are systemic drugs with serious and predictable long-term side effects.
Cortenema is a topical corticosteroid that is less absorbed into the body than oral corticosteroids, and, therefore, it has fewer and less severe side
effects.
Next: Systemic corticosteroids (including side effects) »
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