6.3: Immunosuppressants, Biologics, Monoclonal Antibodies, and Biosimilar Drugs
By the end of this section, you should be able to:
- 6.3.1 Identify the characteristics of immunosuppressants, biologics, monoclonal antibodies, and biosimilar drugs.
- 6.3.2 Explain the indications, actions, adverse reactions, and interactions for immunosuppressant, biologics, monoclonal antibodies, and biosimilar drugs.
- 6.3.3 Describe the nursing implications related to immunosuppressants, biologics, monoclonal antibodies, and biosimilar drugs.
- 6.3.4 Explain the client education related to immunosuppressants, biologics, monoclonal antibodies, and biosimilar drugs.
This section of the chapter will delve into the realm of therapeutic agents used to manage various autoimmune diseases and conditions. Immunosuppressants are drugs that suppress the immune system, helping to prevent organ rejection in transplant recipients and manage autoimmune disorders. Biologic drugs , including monoclonal antibodies , represent a class of medications derived from living organisms that target specific molecules or cells involved in autoimmune processes, offering highly targeted and personalized treatment options. Biosimilar drugs , which are biologic medications designed to be highly similar to already approved biologics, provide cost-effective alternatives with comparable efficacy and safety profiles.
Immunosuppressant Drugs
Immunosuppressant is a class of medicines that inhibit or decrease the intensity of the immune response in the body. They are commonly prescribed to clients who have received an organ transplant and those with autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. While these medications can effectively prevent rejection of transplanted organs and manage symptoms of autoimmune diseases, they also come with potential adverse effects. Clients taking immunosuppressants may be at higher risk for infections, including opportunistic infections that can be life-threatening.
It is important for clients who are taking immunosuppressant drugs to work closely with their health care provider to monitor any potential side effects and receive regular follow-ups. Additionally, steps should be taken to minimize the risk of infection, such as practicing good hygiene and avoiding close contact with sick clients. Overall, while immunosuppressant drugs can be beneficial in certain medical conditions, it is important for clients to weigh the potential benefits against the risks and work closely with their health care provider to ensure safe and effective use.
Glucocorticoids
Glucocorticoids are a steroid hormone produced by the kidneys’ adrenal cortexes that regulate metabolism and the immune system. They have anti-inflammatory and immunosuppressive effects, making them essential in treating inflammatory and autoimmune disorders. Commonly used synthetic glucocorticoids include prednisone and dexamethasone. Glucocorticoids are typically reserved for short-term or last-resort use due to potential toxic effects. Careful tapering is necessary to address potential rebound symptoms resulting from prolonged use (see Table 6.2 for dosing information and Hypothalamus, Pituitary, and Adrenal Disorder Drugs for additional information on glucocorticoids).
Azathioprine
Azathioprine is an immunosuppressant used to treat autoimmune diseases such as rheumatoid arthritis. Azathioprine works by suppressing the immune system, reducing inflammation, and preventing tissue damage. Long-term use has been associated with an increased risk of certain types of cancer. Regular blood tests, such as a complete blood cell count to detect bone marrow suppression or infection, liver function tests to ensure no abnormal liver function is occurring, and serum creatinine to assess proper kidney function, may also be necessary to ensure that the medication is not causing any adverse or harmful effects on the body. See Table 6.3 for additional information on azathioprine.
Mycophenolate
Mycophenolate (also referred to as mycophenolic acid) is an immunosuppressive drug used to prevent organ rejection in clients who have undergone organ transplantation, such as kidney, heart, or liver transplants. It works by inhibiting the proliferation of T and B immune cells, thus suppressing the immune system’s response against the transplanted organs. Mycophenolic acid is commonly used in combination with other immunosuppressants to maintain the function of the transplanted organ and prevent rejection episodes.
Table 6.2 lists common immunosuppressants and typical routes and dosing for adult and pediatric clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Prednisone |
Dosage requirements are variable and individualized based on disease and response of the client; 5–60 mg orally daily.
In situations of less severity, lower doses will generally suffice, while in select clients, higher initial doses may be required. |
|
Dexamethasone
( Decadron ) |
Dosage requirements are variable and individualized based on disease and response of the client; 0.75–9 mg orally daily. |
|
Azathioprine
( Imuran ) |
For rheumatoid arthritis:
1 mg/kg (50–100 mg) orally given as a single dose or twice daily. The dose may be increased, beginning at 6–8 weeks and thereafter in 4-week intervals. Increments should be 0.5 mg/kg orally daily, up to a maximum dose of 2.5 mg/kg orally per day if there are no serious toxicities and if initial response is unsatisfactory.
For renal homotransplantation: Dosing is individualized and based on requirements to prevent rejection and minimize toxicity. Initial dose is 3–5 mg/kg orally daily, beginning at the time of transplant, with dose reduction to maintenance levels of 1–3 mg/kg orally daily. |
|
Mycophenolate
( Cellcept ) |
Children with a BSA 1.25m
2
to <1.5 m
2
: 750 mg orally twice daily (1.5 g total daily dose).
Children with a BSA ≥1.5 m 2 : 1 g orally twice daily (2 g total daily dose). Adults: 1.5 g orally twice daily (total daily dose of 3 g). |
Adverse Effects and Contraindications
Common adverse effects for glucocorticoids include weight gain, increased appetite, mood swings, insomnia, fluid retention, and elevated blood sugar levels. Long-term use can lead to more severe adverse effects, such as osteoporosis, high blood pressure, cataracts, and adrenal insufficiency. Contraindications include systemic fungal infections and live virus vaccines.
Azathioprine adverse effects include nausea, vomiting, diarrhea, and a higher risk of infections due to immune suppression. More severe adverse effects include bone marrow suppression, pancreatitis, and liver toxicity. Contraindications include hypersensitivity to the drug or any of its components and in clients with a genetic deficiency of enzyme TPMT (thiopurine methyltransferase).
Mycophenolate adverse effects include gastrointestinal disturbances (nausea, diarrhea), headaches, and an increased susceptibility to infections. It may also be associated with bone marrow suppression and increased risk of birth defects, making it contraindicated during pregnancy.
Table 6.3 is a drug prototype table for immunosuppressants and antimetabolites featuring azathioprine. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects and contraindications.
|
Drug Class
Immunosuppressant, antimetabolite Mechanism of Action Inhibits DNA synthesis by disrupting the replication and proliferation of T and B immune cells |
Drug Dosage
For rheumatoid arthritis: 1 mg/kg (50–100 mg) orally given as a single dose or twice daily. The dose may be increased, beginning at 6–8 weeks and thereafter in 4-week intervals. Increments should be 0.5 mg/kg orally daily, up to a maximum dose of 2.5 mg/kg orally per day if there are no serious toxicities and if initial response is unsatisfactory. For renal homotransplantation: Dosing is individualized and based on requirements to prevent rejection and minimize toxicity. Initial dose is 3–5 mg/kg orally daily, beginning at the time of transplant, with dose reduction to maintenance levels of 1–3 mg/kg orally daily. |
|
Indications
Management of active rheumatoid arthritis Prevention of rejection in renal homotransplantation Therapeutic Effects Decreases inflammation Suppresses the immune response |
Drug Interactions
Alkylating agents Xanthine oxidase inhibitors Febuxostat Aminosalicylates Angiotensin-converting enzyme (ACE) inhibitors Warfarin Ribavirin Food Interactions No significant interactions |
|
Adverse Effects
Leukopenia/thrombocytopenia/anemia Nausea/vomiting Fever Arthralgias/myalgias Reduction in sperm Hepatotoxicity Increased risk of infection Skin rash Alopecia |
Contraindications
Hypersensitivity Pregnancy and/or breastfeeding Caution: May increase risk of malignancy in clients previously treated with alkylating agents such as cyclophosphamide |
FDA Black Box Warning
Azathioprine
The use of azathioprine increases the risk of malignancy in humans, including post-transplant lymphoma and hepatosplenic T-cell lymphoma.
Mycophenolic Acid
The use of mycophenolic acid increases the risk of fetal toxicity (resulting in pregnancy loss or congenital malformations), malignancies (lymphomas and skin), and susceptibility to bacterial, viral, fungal, protozoal, and opportunistic infections.
Biologic Drugs and Monoclonal Antibodies
Biologic drugs , also known as biologics , are a class of medications derived from living sources such as cells, proteins, or tissues. They are used to treat various medical conditions, particularly autoimmune rheumatic diseases, and certain types of cancer (American Cancer Society, 2018; Drosos et al., 2021). Biologics are different from traditional chemical-based drugs because of their complex structure and the process used to manufacture them, which involves biotechnology and genetic engineering techniques.
Monoclonal antibodies are a type of biologic drug. They are engineered in the laboratory to target and bind to specific molecules or cells in the body, thus exerting precise and targeted effects (American Cancer Society, 2018). Monoclonal antibodies are designed to mimic the immune system’s natural ability to recognize and attack foreign invaders, such as bacteria, viruses, and cancer cells. These antibodies can be used to block certain pathways involved in disease processes, modulate immune responses, or deliver drugs directly to specific cells or tissues.
Both biologic drugs and monoclonal antibodies have revolutionized the treatment of various medical conditions, providing more personalized and effective therapeutic options for clients with complex and difficult-to-treat diseases. However, due to their complex manufacturing process and targeted actions, these medications can be relatively expensive compared to traditional drugs. Additionally, some clients may experience immune-related side effects, and close monitoring is often required during treatment.
Adalimumab
Adalimumab is a monoclonal antibody that targets and inhibits the action of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in inflammation. By blocking TNF-alpha, adalimumab reduces inflammation and alleviates symptoms associated with various autoimmune diseases. See Table 6.4 for dosing information.
Etanercept
Etanercept is another TNF inhibitor that acts as a soluble TNF receptor, binding to and neutralizing TNF-alpha. Like adalimumab, etanercept dampens the inflammatory response and provides relief from autoimmune-related inflammation. See Table 6.5 for additional information.
Infliximab
Infliximab is a chimeric monoclonal antibody that targets TNF-alpha, effectively neutralizing its activity. Infliximab is often used in conditions such as rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel diseases to manage inflammation and improve quality of life. See Table 6.4 for dosing information.
Rituximab
Rituximab is a monoclonal antibody that targets a specific protein known as CD20 found on the surface of B cells. It is primarily used to treat certain types of non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Rituximab works by binding to CD20-positive B cells, leading to the destruction and reduction in cancerous cell growth. It is also used to treat certain autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus. See Table 6.4 for dosing information.
Bevacizumab
Bevacizumab (Avastin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). It is used to treat various types of cancer, including colorectal cancer, lung cancer, kidney cancer, and glioblastoma multiforme (a type of brain tumor). By inhibiting VEGF, bevacizumab disrupts the formation of new blood vessels that tumors need to grow and spread, ultimately slowing down tumor growth and improving outcomes.
Table 6.4 lists common biologic drugs and monoclonal antibodies and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Adalimumab
( Humira ) |
RA, AS, PsA 10–<15 kg:
10 mg subcutaneously every other week.
RA, AS, PsA 15–<30 kg: 20 mg subcutaneously every other week. RA, AS, PsA ≥30 kg: 40 mg subcutaneously every other week. |
|
Etanercept
( Enbrel ) |
Adult RA, AS, PsA:
50 mg subcutaneously weekly.
Adult PsO: Starting dose 50 mg subcutaneously twice weekly for 3 months. Maintenance dose: 50 mg subcutaneously once weekly. |
| Infliximab ( Remicade ) | 5 mg/kg given as an intravenous induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. |
|
Rituximab
( Rituxan ) |
First infusion:
50 mg/hour intravenously. In the absence of infusion toxicity, increase infusion rate by 50 mg/hour increments every 30 minutes, to a maximum of 400 mg/hour.
Subsequent i nfusion: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hour increments at 30-minute intervals, to a maximum of 400 mg/hour. |
|
Bevacizumab
( Avastin ) |
Dosing is individualized and depends on the type of cancer being treated and the combination of other chemotherapy drugs being used.
5–15 mg/kg intravenously every 2–3 weeks. |
Adverse Effects and Contraindications
Common adverse effects of biologic drugs and monoclonal antibodies include increased risk of infections (bacterial, viral, fungal, and opportunistic infections), injection site reactions (erythema, itching, pain, and swelling), diarrhea, rash, pruritis, anemia, leukopenia, thrombocytopenia, congestive heart failure, lymphomas and certain types of skin cancer (melanoma and non-melanoma), convulsions, headache, interstitial lung disease, cutaneous vasculitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis. Contraindications include hypersensitivity to the drug or any of its components, active infection, sepsis, pregnancy, and breastfeeding.
Table 6.5 is a drug prototype table for biologic, TNF inhibitors featuring etanercept. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Biologic, TNF inhibitor Mechanism of Action Blocks the binding of TNF-α and TNF-β (lymphotoxin-α [LT-α]) to cell surface TNF receptors, resulting in the inactivation of TNF’s biological effects |
Drug Dosage
Adult RA, AS, PsA: 50 mg subcutaneously weekly. Adult PsO: Starting dose 50 mg subcutaneously twice weekly for 3 months. Maintenance dose: 50 mg subcutaneously once weekly. |
|
Indications
Rheumatoid arthritis Polyarticular juvenile idiopathic arthritis Psoriatic arthritis Ankylosing spondylitis Plaque psoriasis Therapeutic Effects Decreases inflammation Suppresses the immune response |
Drug Interactions
Live vaccines Anakinra Cyclophosphamide Sulfasalazine Food Interactions No significant interactions |
|
Adverse Effects
Infections, including viral, bacterial, and fungal infection Injection site reactions (erythema, itching, pain, swelling) Diarrhea Rash Pruritis Hematologic (anemia, leukopenia, thrombocytopenia) Congestive heart failure Hepatotoxicity Lymphomas, melanoma, skin cancers, and Merkel cell carcinoma Convulsions Paresthesia Headache Interstitial lung disease Cutaneous vasculitis Stevens–Johnson syndrome Toxic epidermal necrolysis |
Contraindications
Hypersensitivity Active infection or sepsis Pregnancy and/or breastfeeding Caution: May increase risk of malignancy and can increase the risk of reactivating latent tuberculosis |
FDA Black Box Warning
Biologics and Monoclonal Antibodies
Biologic drugs and monoclonal antibodies increase the risk for infections including active tuberculosis and invasive fungal infections as well as bacterial, viral, and other opportunistic infections. They also can increase the risk for certain cancers including lymphomas, melanoma, non-melanoma skin cancer, and Merkel cell carcinoma.
Biosimilar Drugs
Biosimilar drugs are a type of biologic medication that is highly similar to an already approved reference biologic, also known as the original biologic or reference product. Biosimilars are designed to have similar efficacy, safety, and quality as the reference product (American Cancer Society, 2018; U.S. Food and Drug Administration, 2023). They are developed to be equivalent in terms of structure, biological activity, and clinical effects.
Unlike generic versions of traditional chemical-based drugs, which are identical to their reference products, biosimilars are not exact copies due to the complexity of biologics and the variability in the manufacturing process. Biosimilars undergo rigorous testing and comparison to the reference product to ensure they are highly similar and have no clinically meaningful differences in terms of safety and efficacy.
Biosimilars offer an opportunity to increase access to effective biologic treatments at potentially lower costs compared to the reference products. They play a crucial role in promoting competition and driving down prices, making biologic therapies more affordable for clients and health care systems.
Regulatory authorities, such as the U.S. Food and Drug Administration (FDA), have established robust guidelines for the approval of biosimilars, ensuring they meet stringent standards for quality, safety, and efficacy (American Cancer Society, 2018). This regulatory framework ensures that clients can have confidence in the safety and effectiveness of biosimilar medications.
Pegfilgrastim
Pegfilgrastim is a medication used to reduce the risk of infection in clients undergoing certain cancer treatments, such as chemotherapy, that may cause a decrease in the body's white blood cell count. It is a long-acting form of filgrastim, a synthetic version of a natural protein called granulocyte-colony stimulating factor (G-CSF).
Pegfilgrastim stimulates the bone marrow to increase white blood cell production, particularly neutrophils, which are essential for fighting infections. By increasing the white blood cell count, pegfilgrastim helps to reduce the likelihood of severe infections during cancer treatment. See Table 6.7 for additional information.
Table 6.6 lists common biosimilar drugs along with the typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Bortezomib
( Velcade ) |
Dosage requirements are variable and individualized based on disease and response of the client.
1.3 mg/m 2 intravenously at a concentration of 1 mg/mL in 3- to 5-second bolus. |
|
Pegfilgrastim
( Neulasta ) |
For clients receiving myelosuppression chemotherapy:
6 mg subcutaneously once per chemotherapy cycle.
For clients with hematopoietic subsyndrome of acute radiation syndrome: 2 doses 6 mg each subcutaneously 1 week apart. |
Adverse Effects and Contraindications
Adverse effects of bortezomib include GI effects (nausea, vomiting, diarrhea, constipation, fatigue, weakness, peripheral neuropathy, thrombocytopenia, anemia, neutropenia, fever, chills, and skin reaction). Contraindications include hypersensitivity to the drug or any of its components, severe liver impairment, and pregnancy and/or breastfeeding.
Adverse effects of pegfilgrastim also include bone pain, pain in the arms and legs, headache, fatigue and weakness, nausea, and injection site reactions (pain, erythema, and swelling). Contraindications include hypersensitivity to the drug or any of its components, pregnancy, and breastfeeding.
Table 6.7 is a drug prototype table for biosimilar drugs featuring pegfilgrastim. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Biosimilar, granulocyte-colony stimulating factors (G-CSFs) Mechanism of Action Binds to the precursor receptor cells on the surface of bone marrow cells, thereby signaling the bone marrow to increase the production and release of neutrophils into the bloodstream |
Drug Dosage
For clients receiving myelosuppression chemotherapy: 6 mg subcutaneously once per chemotherapy cycle. For clients with hematopoietic subsyndrome of acute radiation syndrome: 2 doses 6 mg each subcutaneously 1 week apart. |
|
Indications
Clients with cancer receiving myelosuppression chemotherapy Clients with hematopoietic subsyndrome of acute radiation syndrome Therapeutic Effects Increases production of white blood cells, particularly neutrophils |
Drug Interactions
No significant interactions Food Interactions No significant interactions |
|
Adverse Effects
Splenic rupture Bone pain Pain in extremities Headache Fatigue Nausea Injection site reactions (pain, erythema, and swelling) |
Contraindications
Hypersensitivity Pregnancy and/or breastfeeding |
Nursing Implications
The nurse should do the following for clients who are taking immunosuppressants, biologics, monoclonal antibodies, and biosimilar drugs:
- Review the client’s medical history to assess allergies and contraindications or potential drug interactions with current medications.
- Monitor complete blood counts for leukopenia, thrombocytopenia, and anemia; liver function tests for hepatotoxicity; renal functions tests for nephrotoxicity; and lipids for elevated lipid levels.
- Evaluate the client’s tuberculosis (TB) status prior to administering biologic drugs, as they can increase the risk of reactivating latent tuberculosis.
- Educate the client about the drug’s purpose, potential side effects, and benefits to help the client make an informed decision about the treatment plan.
- Ensure proper administration technique including the appropriate route, dosage, and injection site. Maintain proper aseptic technique throughout the procedure to prevent infections and ensure client safety.
- After administration, closely monitor the client for any immediate adverse reactions, such as allergic responses or infusion-related reactions. Vital signs, signs of infection, and changes in the client's condition should be regularly assessed, and any concerns should be promptly reported to the health care provider.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an immunosuppressant, biologic drug, monoclonal antibody, or biosimilar drug should:
- Choose an injection site as recommended by the health care provider, avoiding areas that are bony, bruised, sore, red, scarred, or hard.
- Cleanse the injection area with an alcohol swab/pad and let dry for 30 seconds prior to administering the drug.
- Dispose of needles in an FDA-approved sharps disposal container after use.
- Keep a journal of symptoms and note improved or worsening symptoms.
- Practice good hygiene and avoid contact with sick individuals to decrease the risk of infection.
- Report symptoms of fever, chills, sore throat, and skin rash to the health care provider because these may indicate an adverse reaction to the drug.
- Attend all appointments, undergo recommended blood tests, and report any changes or concerns to the health care provider.
The client taking an immunosuppressant, biologic drug, monoclonal antibody, or biosimilar drug should not:
- Dispose of needles or sharps container in the household trash.
- Reuse needles.
- Stop taking the drug unless directed by the health care provider.
- Get a live vaccine such as measles, mumps, and rubella (MMR) or oral polio vaccine (OPV), as this increases the risk of developing the disease from the immunization.