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Immunosuppressives

Immunosuppressive agents are generally used to reduce rejection of transplanted organs. They are also used in serious, systemic cases of lupus in which major organs such as the kidneys are affected or in which there is severe muscle inflammation or intractable arthritis. Because of their steroid-sparing effect, immunosuppressives may also be used to reduce or sometimes eliminate the need for corticosteroids, thereby sparing the patient from undesirable side effects of corticosteroid therapy.

Immunosuppressives can have serious side effects. Patients need to understand, however, that side effects are dose-dependent and are generally reversible by reducing the dose or stopping the medication.

Types of Immunosuppressives

A variety of immunosuppressive drugs is available to treat lupus. Although they have different mechanisms of action, each type functions to decrease or prevent an immune response. The immunosuppressives most frequently used with SLE patients are:

  • azathioprine (Imuran®).

    Azathioprine, one of the most widely used immunosuppressives for lupus, is an antimetabolite. Antimetabolites work by blocking metabolic steps within immune cells and then interfering with immune function. Used to control the underlying disease process, azathioprine has fewer serious side-effect risks than some other drugs used to control lupus.

  • cyclophosphamide (Cytoxan®).

    An alkylating agent and strong immunosuppressive, cyclophosphamide is reserved for treating lupus with kidney disease or other internal organ involvement. It works by targeting and damaging autoantibody-producing cells, thereby suppressing the hyperactive immune response and reducing disease activity. It has the potential for severe side effects, including risk of serious infection.

  • methotrexate (Rheumatrex®).

    Originally developed as a cancer treatment and later approved for rheumatoid arthritis, methotrexate, like azathioprine, is an antimetabolite. It is predominantly used for lupus arthritis. It requires monitoring of the CBC and liver function tests. To reduce toxicity, daily folic acid is prescribed.

  • cyclosporine (Neoral®).

    Originally developed to prevent the body from rejecting transplanted organs, cyclosporine is now commonly used to treat rheumatic diseases, including lupus. Cyclosporine is an antimetabolite.

  • mycophenolate mofetil (CellCept®). A strong immunosuppressive drug developed to prevent the rejection of transplanted organs, mycophenolate is sometimes used as an alternative to cyclophosphamide for lupus with kidney involvement.

    Mycophenolate works by keeping T and B lymphocytes from replicating.
There are many serious risks associated with the use of immunosuppressives. They include immunosuppression (resulting in increased susceptibility to infection), bone marrow suppression (resulting in decreased numbers of RBCs, WBCs, and platelets), and development of malignancies.

Side/Adverse Effects

Dermatologic: alopecia (cyclophosphamide and methotrexate)

Gastrointestinal: nausea, vomiting, stomatitis, esophagitis, and hepatotoxicity

Genitourinary: hemorrhagic cystitis, hematuria, amenorrhea,* impotence,* and gonadal suppression (cyclophosphamide only) **

Hematologic: thrombocytopenia, leukopenia, pancytopenia, anemia, and myelosuppression

Respiratory: pulmonary fibrosis***

Other: increased risk of serious infections or malignancies

Pregnancy and Lactation

Use of immunosuppressives presents definite risks to the fetus. Female patients should use contraceptive measures during treatment and for 12 weeks after ending azathioprine therapy. Azathioprine may pass into breast milk, and women using this drug should consult with their doctors before breastfeeding.


* temporary or reversible once drug therapy is discontinued
** recovery of function after drug is discontinued is unpredictable
*** with high doses


Considerations for Health Professionals

Assessment:

History: allergy to immunosuppressive drugs, infections, impaired hepatic or renal function, pregnancy, lactation, corticosteroid therapy, immunosuppression, bone marrow suppression, and appropriate contraception

Laboratory data: CBC, differential, platelet count, renal function studies, liver function tests, pulmonary function tests, chest X ray, and electrocardiogram (ECG)

Physical: all body systems to determine baseline data and alterations in function, temperature, pulse, respiration, weight, skin color, lesions, hair, and mucous membranes

Evaluation:

therapeutic response and adverse effects

Administration:

orally or intravenously

Precaution: Drug administration protocols can vary. The nurse must work closely with the prescribing physician to administer the drug safely and to monitor the patient to minimize adverse effects and achieve expected outcomes.

Teaching Points:

See Patient Information Sheet on Azathioprine, Cyclophosphamide, Methotrexate (Rheumatrex®), Cyclosporine (Neoral®), and Mycophenolate Mofetil.




Source: National Institutes of Health, U.S.Dept of Health and Human Services


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