While reviewing the medication list for a new patient with rheumatoid arthritis (RA), you note she has an order for rituximab and methotrexate. A quick search in a nursing drug handbook tells you rituximab is a biotherapy drug indicated for patients with non-Hodgkin’s lymphoma, and methotrexate is classified as a chemotherapy drug.
Why are an increasing number of drugs normally given to cancer patients now being used to treat autoimmune diseases? You’re not chemotherapy “certified,” so you wonder whether you can give these drugs. Do they require special handling precautions?
Autoimmune diseases cause suffering and disability for many persons. New biotherapy drugs and older chemotherapy agents have the potential to ease symptoms and improve quality of life. This article provides the information you need to administer these medications and to teach patients about them.
Understanding autoimmune diseases
Autoimmune diseases occur when the body recognizes its own tissues as foreign and triggers the adaptive (acquired) immune system to attack them. This reaction may occur in only one body system, such as a joint (as in rheumatoid or psoriatic arthritis), or across multiple systems, as in systemic lupus erythematosus (SLE). Autoimmune diseases can cause physical impairment and a decreased quality of life. Although their exact cause remains unknown, experts suspect a combination of factors, such as genetics and the environment, play a role.
The National Institutes of Health estimate that up to 23 million Americans have autoimmune diseases, making them more common than cancer or heart disease. These diseases often are marked by periods of remission alternating with incapacitating exacerbations.
Currently, 80 to 100 autoimmune diseases have been identified, but about 40 other conditions have a suspected autoimmune basis. Besides RA and SLE, common autoimmune diseases include psoriasis, multiple sclerosis (MS), myasthenia gravis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), sarcoidosis, and scleroderma.
How autoimmune diseases are treated
Because no known cure exists, treatment of autoimmune diseases focuses mainly on managing symptoms and achieving remission. Recommendations include lifestyle modifications, such as regular exercise, a well-balanced diet, plenty of sleep, and stress control.
Until recently, pharmacologic treatment was limited to analgesics, nonsteroidal anti-inflammatory drugs, and corticosteroids. But since disease-modifying antirheumatic drugs (DMARDs) were introduced, many patients have experienced better symptom control and improved quality of life. DMARDs essentially are either chemotherapy or biotherapy medications; many traditionally have been used to treat cancer. Their effectiveness against autoimmune diseases is thought to stem from their immunosuppressant or immunomodulating properties.
Chemotherapy drugs exert their effects on rapidly dividing cells, causing cell death at the point where the cell tries to divide. They suppress the immune system and commonly cause neutropenia (an abnormally low neutrophil count). Although these side effects are undesirable in cancer treatment, they may be exactly what patients with autoimmune diseases need. Immunosuppression has led to use of these drugs in patients with autoimmune diseases, although most haven’t been approved by the Food and Drug Administration (FDA) for treating such diseases.
Biotherapy drugs change the relationship between the body and the immune cells—in essence, restoring, augmenting, or modulating the immune system. They either mimic substances normally produced by the body or block other natural substances that are part of the immune system. By interfering with immune reactions, they inhibit key factors that cause immunologic inflammation, such as interferon, tumor necrosis factor, and T-lymphocytes. Thus, they’re effective against inflammation—the hallmark of autoimmune diseases.
A combination of chemotherapy and biotherapy may be used to treat the same disease, with the goal of attacking the disease from different angles. For example, methotrexate (traditionally used for chemotherapy) may be combined with infliximab (a biotherapy drug) to treat rheumatoid arthritis. (See Chemotherapy and biotherapy drugs for autoimmune diseases by clicking the PDF icon above.)
Chemotherapy drugs used for autoimmune diseases
The chemotherapy drugs discussed below commonly are prescribed for patients with autoimmune diseases.
Cyclophosphamide frequently is used to treat RA, MS, lupus, and sarcoidosis. Because it may cause hemorrhagic cystitis, patients typically receive I.V. hydration during administration. Encourage them to drink plenty of fluids and empty their bladders frequently, particularly before going to bed. If they’re taking the drug orally, instruct them to take it early in the morning or in the afternoon to allow adequate time for excretion. Advise them to report the first sign of blood in the urine.
Mercaptopurine is used for inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Patients may need to take this oral medication for months, requiring frequent complete blood counts (CBCs) and liver function tests. Common complaints include significant malaise (which may interfere with activities of daily living) and myelosuppression, which may warrant dosage reductions or dosing delays until blood counts recover.
Methotrexate is approved to treat RA, psoriasis, and cancer; it’s also used to treat MS, lupus, sarcoidosis, and ectopic pregnancy. Dosages vary widely depending on the indication and administration route. Before administering methotrexate, review information on this drug in a current drug manual to make sure the dosages and dosing schedule match the indication for which it’s being used.
Mitoxantrone commonly is used to treat MS and certain cancers. It may cause bluish-green urine discoloration for 24 hours after administration and may turn the sclera blue; warn patients about these unusual side effects. Long-term therapy may lead to cardiotoxicity, which tends to be cumulative. Patients should be monitored regularly using multiple-gated acquisition scans (MUGA) to determine if left ventricular ejection fraction is sufficient to continue therapy. Before each dose, assess patients for shortness of breath, edema, and significant weight gain.
Many chemotherapy drugs (including cyclophosphamide and methotrexate) can cause hair loss, nausea, vomiting, fatigue, and myelosuppression. Although dosages used for autoimmune diseases generally are lower and less toxic than those used in cancer treatment, these adverse effects remain a concern. Monitor patients for signs and symptoms of infection (particularly a fever above 38° C [100.5° F]), as well as myelosuppression, which may cause bleeding, bruising, shortness of breath, and fatigue. Teach patients to report these signs and symptoms promptly.
Biotherapy drugs used for autoimmune diseases
Many people mistakenly believe that because biotherapy drugs work with the body’s immune system, they’re more “natural” and less toxic than chemotherapy. Although adverse effects of these drugs differ from those of chemotherapy, all medications that interfere with the immune system can have unintended and generally undesirable effects. Most biotherapy drugs used for autoimmune diseases are monoclonal antibodies. Although they typically aren’t classified as hazardous, they can cause infusion-related reactions, which can be life-threatening unless recognized and treated immediately.
Rituximab, a monoclonal antibody, was one of the first biotherapies approved for RA. Targeting the CD-20 antibody on the cell surface, it’s potentially effective against diseases with a B-cell component, including SLE and antineutrophil cytoplasmic antibody vasculitis. Rituximab may cause infusion-related reactions, particularly with the first dose. Signs and symptoms of such a reaction include fever, chills, rash, pruritus, headache, nausea, hypotension, and back pain. Typically, patients are premedicated with acetaminophen and diphenhydramine to prevent infusion reactions. Infusions should begin slowly; the flow rate may be increased at 30-minute intervals based on patient tolerance. Stay alert and prepared for infusion reactions, which occur in 35% to 40% of RA patients with the first treatment. Monitor patients carefully and keep emergency equipment at hand.
Infliximab is a tumor necrosis-blocking agent approved for multiple autoimmune diseases. For instance, it’s widely used to treat RA and (in pediatric patients) Crohn’s disease. Patients receiving it are at high risk for severe infection during therapy, particularly if they’re getting concomitant corticosteroids or methotrexate. Teach them how to help prevent infection and which signs and symptoms to report promptly. Hypersensitivity, hepatotoxicity, and myelosuppression also may occur with infliximab infusions.
Natalizumab is a monoclonal antibody approved for MS and Crohn’s disease. Common adverse effects include headache, fatigue, urinary and respiratory tract infections, and arthralgias. This drug can be obtained only through a special prescribing program.
Assessing patients before drug administration
Before administering chemotherapy or biotherapy, carefully evaluate the patient’s history and medication list. (See Who can administer these drugs? by clicking the PDF icon above) To help prevent drug-drug or drug-herbal interactions, perform medication reconciliation. In patients already receiving chemotherapy or biotherapy, assess for drug tolerance and persistent toxicities, which may warrant withholding doses.
Be sure to review laboratory results before giving these drugs. Because they may suppress the immune system, doses should be withheld until the most recent CBC is available, to make sure patients who already have dangerous myelosuppression don’t get further immunosuppressive treatment. Monitor serum creatinine levels and liver function tests routinely to evaluate whether the drug is being metabolized and excreted safely.
Obtaining informed consent
Before treatment begins, make sure your patient has given informed consent. Information to provide for informed consent includes the goal of therapy, medications, adverse effects, approximate duration of therapy, and the option of stopping therapy. Keep in mind that informed consent is an ongoing process that healthcare providers should reinforce with each dose, as many patients receive long-term therapy. Some facilities require patients to give informed consent specific to chemotherapy (similar to a surgical or blood transfusion consent). Be sure to check your facility’s policy on this. Although the physician is responsible for obtaining informed consent, nurses play an important role in providing drug-specific education, answering patients’ questions, and providing simple interpretations of complex information. Be sure to document the patient education you provide during the informed consent process.
Reviewing chemotherapy or biotherapy orders
Review the physician’s order—especially if you’re unfamiliar with the prescribed treatment. Also review the medications to determine if they’re classified as hazardous, so you can find out what handling precautions are required.
Check the ordered dosage carefully, too. Dosages may vary greatly depending on the indication. In many cases, dosages are calculated based on the patient’s weight, and modifications due to toxicity are common. Know that a patient’s reported weight isn’t acceptable for dosage calculation; actual weight must be obtained before the drug is prepared. Never accept verbal orders for chemotherapy or biotherapy drugs, or for orders containing commonly confused abbreviations, because of the potential for life-threatening errors. The electronic health record (EHR) or preprinted orders generally are safer than handwritten orders. If you have questions about the drug, consult a pharmacist.
Chemotherapy agents may be given I.V. because of their toxicity. But many of these drugs, such as cyclophosphamide and methotrexate, are given orally to treat autoimmune diseases. Some are started I.V. and switched to an oral form once the patient is stabilized on them. Most biotherapy drugs used for autoimmune diseases must be given I.V. because of their large molecules.
Verifying or performing dosage calculations
Typically, the nurse verifies the dosage ordered before the drug is mixed and given. It’s standard practice for chemotherapy dosage calculations to be independently double-checked by two nurses before administration, as with blood products or insulin. This safety check helps prevent potentially lethal errors. Although the EHR can aid calculation, many dosing errors stem from incorrect entry of a patient’s weight and height or from failure to use the most current weight (obtained within the past week). Biotherapy dosages generally are based on weight; chemotherapy dosages, on body surface area (BSA), which hinges on both height and weight. At many facilities, BSA calculators are available in the oncology unit to assist with calculations; alternatively, you can find calculators on the Internet. Using a BSA calculator helps prevent mathematical errors.
Administering the drug
To administer a chemotherapy or biotherapy drug, assemble all necessary supplies, perform hand hygiene, and don personal protective equipment (gown, hazardous drug-approved gloves, and possibly mask and eye protection). Make sure emergency equipment is at hand in case of a reaction. Assess the I.V. line for patency, and administer the medication while keeping the system closed. After the infusion, flush the I.V. line well, monitor the patient for acute side effects, and discard used materials in a hazardous waste container.
For patients who will receive an oral medication, consider their ability to tolerate oral medications and their understanding of the importance of adhering to treatment. If appropriate, recommend they use a drug diary or an electronic reminder to ensure they take their drugs as scheduled. Making follow-up phone calls to the patient after a new treatment begins can promote adherence and identify toxicities that the patient may be experiencing.
Recognizing infusion reactions
Two types of infusion reactions may occur in patients receiving monoclonal antibodies—anaphylaxis (hypersensitivity reactions) and cytokine-release syndrome. Anaphylaxis is an allergic reaction to the drug that causes hypotension, itching, shortness of breath, and lightheadedness. Treatment involves stopping the infusion, monitoring the patient’s vital signs and airway, and giving emergency medications and oxygen as required. A patient who’s had anaphylaxis should never receive that medication again.
More commonly, patients receiving monoclonal antibodies experience cytokine-release syndrome—a reaction to release of cytokines from targeted cells. It most often occurs with the first infusion. Manifestations include fever or chills, nausea, hypotension, headache, and dyspnea. Premedicating patients with acetaminophen and diphenhydramine can minimize or prevent this reaction. Patients experiencing this syndrome are treated symptomatically but continue to receive the monoclonal antibody, with the infusion slowed or stopped temporarily while supportive medications are given. Usually, the infusion is completed. Cytokine-release reactions become less severe with subsequent infusions.
Managing other adverse reactions
Chemotherapy and biotherapy drugs commonly cause myelosuppression, including anemia, thrombocytopenia, and neutropenia. Provide education to help patients manage these and other adverse reactions. (See Helping patients cope with side effects by clicking the PDF icon above.)
With all patients, emphasize that these drugs aren’t safe during pregnancy because they can harm the fetus and can be transmitted to sexual partners through body fluids. Instruct all patients to use condoms to prevent sex partners’ exposure to the drug, as well as to prevent pregnancy. Advise them to use a second birth-control method.
Teaching patients about drug therapy
Many patients have stereotypical ideas about chemotherapy based on media portrayals or the experiences of older acquaintances who had chemotherapy before today’s supportive-care medications came into wide use. Patients with autoimmune diseases may be shocked to learn the drug prescribed for them is classified as chemotherapy or biotherapy. To improve patient acceptance and adherence, reassure them that dosages are smaller than those used to treat cancer and that many drug side effects can be managed. Provide detailed instructions on the medication, both verbally and in written form, including the importance of continuing to take it even if side effects arise. Encourage them to notify their healthcare provider of side effects promptly.
Patients who are prescribed hazardous chemotherapy to self-administer at home need special education on drug handling. Instruct them to avoid skin contact with the drug whenever possible and to wash their hands before and after taking the drug, even if it’s oral. Remind them to keep medications away from children and pets.
Be aware that some of these medications, particularly biotherapy drugs, can be quite costly. Sending patients home with a prescription to fill without checking their insurance coverage may result in non-adherence. As appropriate, refer patients who’ve started these therapies to a financial counselor or social worker to ensure they’re able to complete prescribed therapy.
Biotherapy and chemotherapy drugs may give patients with autoimmune disease a better quality of life. If you’re unfamiliar with these medications, educate yourself so you can provide safe, effective treatment.
Before taking the post-test, download the article with the online sidebar “Handling hazardous drugs” by clicking the PDF icon above
Click here for a complete list of references.
Nancy E. Thompson is the Clinical Director of Quality and Performance at the Swedish Cancer Institute in Seattle, Washington.
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