Immunosuppressants: Generic and Brand Names
- Immune Modulators
- fingolimod (Gilenya)
- lenalidomide (Revlimid)
- thalidomide (Thalomid)
- T- and B-Cell Suppressors
- abatacept (Orencia)
- azathioprine (Imuran)
- cyclosporine (Sandimmune)
- tacrolimus (Prograf)
- Interleukin Receptor Antagonist
- anakinra (Kineret)
- Monoclonal Antibodies
- infliximab (Remicade)
- muromonab-CD3 (Orthoclone OKT3)
Immunomodulators
Immune modulators block the chemical signals that run the immune response. They shut down release of the cytokines that drive inflammation and lymphocyte activation, which lowers overall immune activity.
Lenalidomide and thalidomide cut proinflammatory cytokine secretion and push anti-inflammatory cytokines out of monocytes; thalidomide treats multiple myeloma and erythema nodosum leprosum. Fingolimod holds lymphocytes inside the lymph nodes so they cannot reach peripheral blood and mount immune or inflammatory reactions, and it was the first oral agent for relapsing forms of multiple sclerosis.
Pharmacokinetics
Here are the characteristic interactions of immune modulators and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| PO | Slow | 12-16 h | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 6-9 d | Liver | Urine |
Contraindications and Cautions
Pregnancy is the hard contraindication. These agents cause serious fetal harm. Thalidomide and lenalidomide are powerful human teratogens (thalidomide causes phocomelia and other severe birth defects after even a single dose), so both are dispensed only through a mandatory FDA Risk Evaluation and Mitigation Strategy (REMS) program that requires prescriber, pharmacy, and patient enrollment, documented contraception, and pregnancy testing. Lenalidomide also carries boxed warnings for hematologic toxicity and for venous and arterial thromboembolism.
T- and B-Cell Suppressors
These drugs blunt cell-mediated immunity. The exact mechanism is not fully understood, but they block antibody production by B cells, inhibit suppressor and helper T cells, and alter the release of interleukins and T-cell growth factor. The main use is preventing and treating specific transplant rejection.
Pharmacokinetics
Here are the characteristic interactions of T- and B-cell suppressors and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| PO | Varies | 3.5 h | N/A |
| IV | Rapid | 1-2 h | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 19-27 h | Liver | Bile |
Contraindications and Cautions
Hold for known allergy to the drug or its components (hypersensitivity risk) and during pregnancy or lactation (serious effects on fetus or neonate). Use caution in renal or hepatic impairment, which slows metabolism and excretion, and in known neoplasms, which can spread once the immune system is suppressed.
Adverse Effects
Expect a higher risk of infection and new neoplasms. Other effects: headache and tremors (CNS), hypertension (CV), pulmonary edema (respiratory), hepatotoxicity, GI upset, and diarrhea (GI), and renal toxicity or dysfunction (GU).
Interactions
Stacking other hepatotoxic or nephrotoxic drugs raises combined toxicity.
Interleukin Receptor Antagonist
Interleukin receptor antagonists block the interleukins released during an inflammatory or immune response. The only one available is anakinra (Kineret). It antagonizes human interleukin-1 receptors and shuts down interleukin-1 activity; IL-1 climbs during inflammatory or immune reactions and is thought to drive the cartilage breakdown seen in rheumatoid arthritis.
It is indicated for reducing signs and symptoms of moderately to severely active rheumatoid arthritis in patients 18 years of age and older who have not responded to traditional treatment.
Pharmacokinetics
Here are the characteristic interactions of interleukin receptor antagonist and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Subcutaneous | Slow | 3-7 h | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 4-6 h | Tissues | Urine |
Contraindications and Cautions
Hold for known allergy to E-coli-produced products or to the drug itself (hypersensitivity risk). Use caution in pregnancy and lactation, since the drug may cross the placenta and enter breast milk, and in renal impairment, immunosuppression, or active infection, all of which the drug worsens.
Adverse Effects
Sinusitis (EENT), headache (CNS), upper respiratory tract infections (respiratory), nausea and diarrhea (GI), and injection-site reactions (skin).
Interactions
Combining with etanercept (Enbrel) carries a real risk of severe, life-threatening infections, and serious infection risk rises with other immune-acting drugs.
Monoclonal Antibodies
Monoclonal antibodies bind specific receptor sites to act as immune suppressors. They react against human T cells, disabling them. Muromonab-CD3 (Orthoclone OKT3) was the first monoclonal antibody approved for use in humans and was indicated for acute allograft rejection in heart or liver transplant patients. Note that its manufacturer voluntarily withdrew muromonab-CD3 from the United States market in 2010 because of frequent severe reactions, including cytokine release syndrome, and the arrival of better-tolerated humanized agents; you will not administer it today, but it still appears on exams as a historical first.
Pharmacokinetics
Here are the characteristic interactions of monoclonal antibodies and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV | Minutes | 2-7 d | 7 d |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 47-100 h | Tissues | Urine |
Contraindications and Cautions
Hold for known allergy to the drug or to murine products (hypersensitivity risk). Use caution in fluid overload, which the drugs can worsen, and in pregnancy and lactation (effects on fetus or neonate). Prior dosing of a monoclonal antibody raises the chance of a serious hypersensitivity reaction on repeat administration.
Adverse Effects
The dangerous one is acute pulmonary edema tied to severe fluid retention and cytokine release syndrome (flu-like symptoms that can progress to third-spacing of fluids and shock). Also nausea, diarrhea, and vomiting (GI), myalgia (musculoskeletal), and fever, chills, malaise, and increased susceptibility to infection and cancer. Eculizumab can trigger intravascular hemolysis with fatigue, pain, dark urine, shortness of breath, and blood clots.
Interactions
Pairing with other immunosuppressants causes severe immune suppression with more infections and neoplasms.
Nursing Considerations for Immunosuppressants
Nursing Assessment
Screen for contraindications and cautions: allergy history, pregnancy or lactation, renal and hepatic impairment, and any history of neoplasms. Get a baseline physical exam, and check the skin for lesions to catch early dermatologic effects. Weigh the patient to track fluid retention and monitor temperature for infection. Assess CNS status, and check pulse, blood pressure, and perfusion for bleeding or cardiovascular effects. Monitor CBC and liver and renal function tests for dose adjustment and for changes in bone marrow function.
Nursing Diagnoses
- Acute pain related to CNS, GI, and flu-like effects
- Imbalanced nutrition: less than body requirements related to nausea and vomiting
- Anxiety related to diagnosis and drug therapy
Nursing Interventions
Draw CBC and differential before therapy and periodically during it to track drug and adverse effects. Give the drug as ordered, and teach the patient or a family member to inject it if the patient cannot. Protect the patient from infection and hold strict aseptic technique for any invasive procedure during immunosuppression. Arrange supportive care and comfort measures (rest, environmental control) to ease discomfort and keep the patient on therapy. Teach drug effects and warning signs to build understanding and compliance.
Evaluation
Track response to therapy (improvement in the treated condition) and watch for adverse effects (flu-like symptoms, GI upset, more infections, neoplasms). Confirm understanding by having the patient name the drug, its indication, and the adverse effects to watch for, and monitor compliance.
Frequently Asked Questions
Why do immunosuppressants raise the risk of infection and cancer? They deliberately blunt immune surveillance so the body will not reject a transplant or attack its own tissue. The same suppression that prevents rejection also lowers defenses against pathogens and against abnormal cells, so infection and new malignancies are expected long-term risks that drive the whole plan of care.
What are the four classes covered here? Immune modulators (such as fingolimod, lenalidomide, and thalidomide), T- and B-cell suppressors (such as cyclosporine, tacrolimus, and azathioprine), interleukin receptor antagonists (anakinra), and monoclonal antibodies (such as infliximab).
Which immunosuppressants require a REMS program? Thalidomide and lenalidomide are dispensed only through a mandatory FDA REMS because they are potent teratogens. Prescribers, pharmacies, and patients must enroll, and patients of childbearing potential need documented contraception and pregnancy testing.
Why are cyclosporine and tacrolimus levels monitored so closely? Both are calcineurin inhibitors with a narrow therapeutic index and significant nephrotoxicity. Blood levels guide dosing so the transplant stays protected without tipping the patient into renal injury, hypertension, or neurotoxicity.
Is muromonab-CD3 (Orthoclone OKT3) still used? No. It was the first monoclonal antibody approved for humans but was voluntarily withdrawn from the US market in 2010 because of severe cytokine release reactions and the availability of better-tolerated agents. It remains a common exam fact.
What teaching protects a patient on these drugs? Stress strict infection precautions, prompt reporting of fever or signs of infection, avoidance of live vaccines, sun protection and skin checks for new lesions, correct injection and storage technique where relevant, and keeping every lab and follow-up appointment.