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Cytotoxic/Immunosuppresive Drugs

Sometimes severe skin disease is damaging internal organs, ruining

the enjoyment of life or risking serious infection. These problems

usually require strong medication for a long time. Often a choice is

made between the certain damage of a steroid drug, such as

prednisone, and the possible damage of a cytotoxic drug.

While some of the side effects of Imuran (azathioprine), Cytoxan

(cyclophosphamide) and other immunosuppressive and cytotoxic drugs

are severe, 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

treatment. They can help to prolong life, preserve function, reduce

symptoms, and sometimes may serve to put the disease into remission.

Immunosuppressive and cytotoxic drugs are used for two major

reasons. First, they are potent drugs which help to reduce disease

activity in skin or internal organs. Second, they may reduce or

sometimes eliminate the need for steroids (cortisone derivatives

such as prednisone). Steroids used alone to treat major 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 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 autoimmune diseases and vasculitis 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 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 in 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. Drugs to reverse the toxic effects on the blood and

immune system can be given if needed.

Imuran

Imuran is less potent and less effective than Cytoxan, but it has

far fewer side effects. Its use may case the white blood cell count,

platelet count, or red blood cell count to decrease, and it might

slightly 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 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. One in 300

people can't remove Immuran from their systems, and the quickly

develop side effects.

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 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, blisering skin condition. It can cause

hair loss. Like Imuran, the 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 disease and my help to avoid some of the side

effects that occur with daily 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 state, 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 5 to 15 milligrams per week. Methotrexate is well

tolerated by most patients. 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

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