Generic and Brand Names
Interferons: interferon-alpha-2b (Intron-A), interferon-alfacon-1 (Infergen), interferon-alfa-n3 (Alferon N), interferon-beta-1a (Avonex), interferon-beta-1b (Betaseron), interferon-gamma-1b (Actimmune), peginterferon alfa-2b (Peg-Intron).
Interleukins: aldesleukin (Proleukin), oprelvekin (Neumega). Note that oprelvekin (Neumega), the recombinant interleukin-11 used to prevent severe chemotherapy-induced thrombocytopenia, has been discontinued in the United States, so you are unlikely to administer it; the thrombopoietin receptor agonist romiplostim (Nplate) is now used off-label for that purpose.
Colony-stimulating factors: filgrastim (Neupogen), pegfilgrastim (Neulasta), sargramostim (Leukine).
Interferons
Interferons are naturally produced and released by human cells invaded by viruses, and also by cells responding to other stimuli such as cytotoxic T-cell activity. Recombinant DNA technology has made a number of them available for use.
Therapeutic Action
Interferons prevent virus particles from replicating inside cells, stimulate interferon receptor sites on non-invaded cells to produce antiviral proteins that block viral entry, inhibit tumor growth and replication, stimulate cytotoxic T-cell activity, and enhance the inflammatory response. Interferon gamma-1b also acts like an interleukin, making phagocytes more aggressive.
Indications
Chronic hepatitis C in adults, multiple sclerosis in adults, and leukemias, Kaposi sarcoma, warts, AIDS-related complex, and malignant melanoma.
By age group: most immune modulators are not recommended or not tested in children; exceptions (interferon alfa-2b, azathioprine, cyclosporine, tacrolimus, palivizumab) are used cautiously because of toxic effects on the GI, renal, hematological, or central nervous systems, and active children should be protected from infection and injury. In adults, stress avoiding infection and keeping regular followup, teach proper injection technique, needle disposal, and storage, and note that these drugs are contraindicated in pregnancy and lactation (fetal abnormalities, increased maternal and fetal infections, suppressed immune responses in nursing infants); women of childbearing age should use barrier contraceptives, since some drugs also impair fertility. In older adults, the aging immune system makes them more susceptible to immunomodulator effects, so monitor closely for GI, CNS, renal, and hepatic toxicity and teach infection and injury avoidance.
Pharmacokinetics
Here are the characteristic interactions of interferons and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IM, subcutaneous | Rapid | 3-12 h | N/A |
| IV | Rapid | End of infusion | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 2-3 h | Kidney | Unknown |
Contraindications and Cautions
Allergy to any interferon or product component (hypersensitivity risk). Pregnancy and lactation (adverse effects on neonate or mother). Cardiac disease, since hypertension and arrhythmias have been reported. Myelosuppression, since these drugs can suppress bone marrow. CNS dysfunction of any kind, given reported CNS depression and personality changes.
Adverse Effects
Flu-like syndrome (lethargy, myalgia, arthralgia, anorexia, nausea), CNS effects (headache, dizziness, bone marrow depression, depression and suicidal ideation), liver impairment, and photosensitivity.
Interactions
No reported clinically important drug-drug interactions.
Interleukins
Interleukins are synthetic compounds that communicate between lymphocytes, stimulating cellular immunity and inhibiting tumor growth. Interleukin-2 boosts cellular immunity by increasing the activity of natural killer cells, platelets, and cytokines.
Therapeutic Action
Increase the number of natural killer cells and lymphocytes, cytokine activity, and circulating platelets.
Indications
Specific renal carcinomas in adults, and prevention of severe thrombocytopenia.
Pharmacokinetics
Here are the characteristic interactions of interleukins and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV | 5 min | 13 min | 3-4 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 85 min | Kidney | Urine |
Contraindications and Cautions
Allergy to any interleukin or E-coli-produced product (hypersensitivity risk). Pregnancy, since these drugs were embryocidal and teratogenic in animal studies. Lactation, since it is unclear whether they cross into breast milk. Renal, liver, or cardiovascular impairment, given adverse effects of the drug.
Adverse Effects
Flu-like effects (lethargy, myalgia, arthralgia, fatigue, fever), CNS changes, respiratory difficulties, and cardiac arrhythmia. Oprelvekin has been associated with severe hypersensitivity reactions; instruct patients to report difficulty breathing or swallowing, chest tightness, or swelling.
Interactions
No reported clinically important drug-drug interactions.
Colony-Stimulating Factors
Colony-stimulating factors are produced by recombinant DNA technology. They increase production of neutrophils and activate mature granulocytes and monocytes.
Therapeutic Action
Increase production of white cells.
Indications
Reduce infection incidence in bone marrow suppression, decrease neutropenia associated with bone marrow transplants and chemotherapy, and treat various blood-related cancers.
Pharmacokinetics
Here are the characteristic interactions of colony-stimulating factors and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV | N/A | 2 h | 4 d |
| Subcutaneous | N/A | 8 h | 4 d |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 210-231 minutes | Unknown | Unknown |
Contraindications and Cautions
Allergy to any interleukin or E-coli-produced product (hypersensitivity risk). Sargramostim is contraindicated in neonates (benzyl alcohol in the solution) and with excessive leukemoid myeloid blasts in the bone marrow or peripheral blood, which the drug could worsen; use caution in hepatic or renal failure, which can alter its pharmacokinetics. Pregnancy and lactation, since effects on the fetus or neonate are not known.
Adverse Effects
CNS (headache, fatigue, generalized weakness), GI (nausea, vomiting, diarrhea, constipation, anorexia), skin (alopecia, dermatitis), and musculoskeletal (generalized pain, bone pain).
Interactions
Lithium or corticosteroids increase sargramostim's myeloproliferative effects.
Nursing Considerations
Nursing Assessment
Assess for contraindications and cautions (allergy, pregnancy and lactation status, hepatic, renal, or cardiac disease, leukemic states) to avoid adverse effects. Establish a baseline physical assessment, and assess for skin lesions to catch early dermatological effects. Obtain weight to monitor for fluid retention, monitor temperature to detect infection, and evaluate CNS status. Monitor CBC and renal and liver function to guide dose adjustment and identify 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 flu-like effects; and anxiety related to diagnosis and drug therapy.
Implementation
Arrange lab tests before and periodically during therapy, including CBC and differential, to monitor for drug and adverse effects. Monitor for severe reactions such as hypersensitivity, and discontinue the drug immediately if they occur. Administer as indicated, and teach the patient or a significant other to give injections so the drug is delivered even when the patient cannot self-administer. Arrange supportive care and comfort measures (rest, environmental control) to help the patient cope. Provide patient education on drug effects and warning signs to build knowledge and compliance.
Evaluation
Monitor patient response (improvement in the condition treated) and watch for adverse effects (flu-like symptoms, GI upset, CNS changes, bone marrow depression). Confirm understanding by having the patient name the drug, its indication, and adverse effects to watch for, and monitor compliance.
Frequently Asked Questions
What is the difference between immunostimulants and immunosuppressants? Both are immunomodulators. Immunostimulants energize an exhausted or underactive immune system to fight infection, cancer, or low white cell counts, while immunosuppressants deliberately turn immune activity down to prevent transplant rejection or treat autoimmune disease.
What are the three main classes of immunostimulants? Interferons, interleukins, and colony-stimulating factors. Interferons block viral replication and slow tumor growth, interleukins boost natural killer cell and lymphocyte activity, and colony-stimulating factors such as filgrastim drive the bone marrow to make more neutrophils.
Why are colony-stimulating factors given during chemotherapy? Drugs like filgrastim (Neupogen) and pegfilgrastim (Neulasta) reduce the risk of febrile neutropenia by stimulating neutrophil production, which protects patients whose marrow is suppressed by myelosuppressive chemotherapy.
What is the most common adverse effect patients report on these drugs? A flu-like syndrome with fever, chills, myalgia, arthralgia, fatigue, and headache is the most frequent complaint across interferons, interleukins, and colony-stimulating factors. Bone pain is also common with colony-stimulating factors as the marrow ramps up.
Why must patients on interferons be screened for depression? Interferons can cause CNS depression, mood changes, and suicidal ideation. Assess baseline mental health, teach patients and families the warning signs, and report new or worsening depression promptly.
Is oprelvekin (Neumega) still used? No. Oprelvekin has been discontinued in the United States. Romiplostim (Nplate) is now used off-label to raise platelet counts in patients receiving chemotherapy.