http://www.hamline.edu/~wnk/lupus/articles/Imuran,_Cytoxan_and_Related_Drugs.html

Imuran, Cytoxan And Related Drugs

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Robert S. Katz, M.D.
Presbyterian St. Lukes Medical Center
St. Luke's/Roosevelt Hospital Center
Associate Professor, Rush Medical College
Chicago, Illinois

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Why would anyone take a medicine that might cause their white blood cell
count or platelet count to fall abruptly, leading to increased
susceptibility to infections or a tendency to bleed? Why would anyone
take a medicine that might, to a small extent, predispose them to
develop certain cancers? People with lupus take them because these
medications can be very helpful, especially in cases where the kidneys
or other major organs are involved.
While some of the side effects of Imuran (azathioprine), Cytoxan
(cyclophosphamide) and other immunosuppressive and cytotoxic drugs are
noted above, they are generally reversible by either reducing the dosage
or stopping the medication. Although immunosuppressive drugs can have
serious side effects, they can be of great value in the treatment of
lupus. They can help to prolong life, preserve kidney function, reduce
symptoms, and sometimes may serve to put the disease into remission.
These drugs help to reduce symptoms and damage to vital organs, such as
the kidney, until a natural remission occurs. They sometimes help to
achieve a remission earlier.

Immunosuppressive and cytotoxic drugs are sometimes used in the
treatment of systemic lupus erythematosus (SLE) for two major reasons.
First, they are potent drugs which help to reduce disease activity in
major organs such as the kidney. Second, they may reduce or sometimes
eliminate the need for steroids (cortisone derivatives such as
prednisone). Steroids used alone to treat major organ involvement must
sometimes be given in high doses. This increases the risk of both
short-term and long-term side effects, which may sometimes be worse than
the disease itself. Immunosuppressive drugs can be used either in
addition to, or instead of, steroids or to lower the amount of steroid
needed and often spare the patient the undesirable side effects of
steroid therapy.

HOW DO THEY WORK?
Cells in the body divide and grow at varying rates. Examples of rapidly
dividing cells include, the antibody producing cells of the immune
system, blood cells, hair cells, gonadal cells and malignant cells.
Cytotoxic (cyto=cell, toxic=damage) drugs work by targeting and damaging
cells which grow at a rapid rate. In lupus, the immune system is
hyperactive and produces auto-antibodies at a rapid rate of growth.
Cytotoxic medicines have their greatest effect against rapidly dividing
cells and, therefore, can be beneficial in the treatment of lupus by
suppressing the cells involved in the hyperactive immune response. The
effect is a reduction in disease activity. There are risks associated
with the use of cytotoxic drugs. The immune system may be suppressed too
much and cause an increased susceptibility to infections such as
shingles and pneumonia. The bone marrow may be suppressed and result in
reductions in red blood cells, white blood cells and platelets.
Suppression of hair cell growth may lead to a net loss of hair. The
cytotoxic effects on gonadal cells may lead to sterility.

IMURAN
Imuran is less potent and less effective than Cytoxan, but it has far
fewer side effects. Its use may cause the white blood cell count,
platelet count, or red blood cell count to decrease, and it might
increase the risk of developing lymphoma (a cancer involving the lymph
glands, liver and spleen). However, it is well tolerated in most cases.
Blood tests to determine the white blood cell, platelet and red blood
cell count should be taken regularly in patients receiving Imuran.
Adjustments in dosage are made if the tests indicate a serious decrease
in the blood count.
Imuran is also used to treat lupoid hepatitis, rheumatoid arthritis and
other autoimmune disorders, and to reduce the amount of steroids given.

CYTOXAN
Cytoxan may cause many side effects, but it is well tolerated by most
patients. Like Imuran, it may cause an upset stomach and its use may
cause the white blood cell count, platelet count, or red blood cell
count to decrease. Blood tests to determine the white blood cell,
platelet and red blood cell count should be taken each month in patients
receiving Cytoxan. If the blood count is seriously decreased, the dosage
is adjusted and the blood counts will generally return toward normal.

Patients receiving treatment with Cytoxan have an increased risk of
developing malignancies including leukemia, bladder cancer, and other
tumors. Cytoxan may also cause temporary or permanent sterility in both
women and men, preventing them from having children. It may also cause
damage to a developing fetus if a woman gets pregnant unintentionally
while being treated with the drug. Use of Cytoxan may cause bleeding
from the bladder, but this usually can be prevented by drinking large
amounts of water. Cytoxan also predisposes a patient to develop
shingles, which is a painful, blistering skin condition. It can cause
hair loss. Like Imuran, use of Cytoxan may predispose a patient to
develop unusual infections, particularly when it is used in combination
with high doses of steroids.

A typical daily dose of Imuran or Cytoxan is 125 to 150 milligrams (mg)
a day given orally. A low dose is 75 mg or less. Cytoxan should be taken
in the morning with fluid and should not be taken at night, when fluid
intake is low. Cytoxan and Imuran are not used together except in
certain experimental conditions. Cytoxan (but not Imuran) can be given
at a much higher dose intravenously on a monthly basis. This may be
quite effective for severe kidney disease and may help to avoid some of
the side effects that occur with daily oral dosages of this drug.

RELATED DRUGS
Other cytotoxic drugs related to cyclophosphamide (Cytoxan) are
chlorambucil (Leukeran) and nitrogen mustard (Mustargen). Leukeran has
similar side effects to Cytoxan. As previously stated, lupus patients
taking cyclophosphamide (Cytoxan), azathioprine (Imuran), chlorambucil
(Leukeran) or nitrogen mustard (Mustargen) need to have their blood
counts monitored each month. In response to the lab tests and side
effects, drug dosage is adjusted to prevent or reverse any serious
toxicity.
Methotrexate is usually given orally once a week, although it may also
be given by injection. The dosage is generally 7.5 to 20 milligrams per
week. Methotrexate is well tolerated by most patients. Its use in lupus
has not been thoroughly tested, but it is given quite commonly for
rheumatoid arthritis and has been shown to produce improvement of joint
pain and stiffness. It does not predispose a patient to develop
malignancies. However, liver disease and lung reactions can occasionally
occur with the use of methotrexate and it can be sun sensitizing. Dosage
may need to be decreased if kidney disease is present. Blood counts
should also be taken each month in patients receiving this drug and
dosage modified if side effects are detected.

CONCLUSION
While cytotoxic medications are not needed and should not be used in
cases of mild lupus, these medications can be very helpful in cases
where the kidneys or other major organs are involved, or in cases where
the lupus is quite active and symptomatic. Sometimes a kidney biopsy or
other tissue biopsy is necessary before deciding whether to use these
medications. Even in more serious cases of major organ involvement, they
should not be used indefinitely without good reason.
Therefore, it is important to assess the beneficial effects as well as
the risks involved in cytotoxic drug therapy. Doctors use the term
"risk-benefit ratio" to describe the comparison of side effects to
beneficial effects of medications. While these drugs are not
FDA-approved, they are commonly used and accepted as standard practice.
People with lupus should discuss the riskªbenefit ratio of these
medications with their physician.

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Last modified: 2001-01-03