IL-2
aldesleukin (interleukin-2, IL-2)
Pharmacologic class: Interleukin-2 (IL-2), human recombinant (cytokine)
Therapeutic class: Antineoplastic (miscellaneous)
Pregnancy risk category C
FDA Box Warning
• Give only to patients with normal cardiac and pulmonary function, as shown by thallium stress testing and pulmonary function testing. Use extreme caution when giving to patients with normal thallium stress test and normal pulmonary function tests who have a history of cardiac or pulmonary disease.
• Give under supervision of physician experienced in cancer chemotherapy, in setting where intensive care facilities and cardiopulmonary or intensive care specialists are available.
• Drug is linked to capillary leak syndrome, which causes hypotension and reduced organ perfusion (possibly severe and resulting in death).
• Before starting drug, preexisting bacterial infections must be treated, because drug may impair neutrophil function and increase disseminated infection risk. Patients with indwelling central lines are at special risk for infection with gram-positive microorganisms. Prophylactic antibiotics can help prevent staphylococcal infections.
• Withhold drug in patients who develop moderate to severe lethargy or somnolence; continued administration may cause coma.
Action
Activates cellular immunity and inhibits tumor growth by increasing lymphocytes and cytokines, which lyse tumor cells
Availability
Injection: 22 million international units/vial
Indications and dosages
➣ Metastatic renal cell carcinoma and metastatic melanoma
Adults older than age 18: 600,000 international units/kg I.V. given over 15 minutes q 8 hours for a maximum of 14 doses, followed by 9 days of rest. Repeat for another 14 doses, for a maximum of 28 doses per course.
Off-label uses
• Colorectal cancer
• Kaposi's sarcoma
• Non-Hodgkin's lymphoma
Contraindications
• Hypersensitivity to drug
• Arrhythmias, cardiac tamponade, seizures, severe GI bleeding, coma or toxic psychosis lasting more than 48 hours
• Organ allograft
• Abnormal thallium stress test or pulmonary function test results
Precautions
Use cautiously in:
• anemia, bacterial infections, heart disease, CNS metastases, hepatic disease, pulmonary disease, renal disease, thrombocytopenia
• pregnant or breastfeeding patients
• children.
Administration
• Make sure patient's thallium stress test and pulmonary function test results are normal before giving.
See Don't give if patient is drowsy or severely lethargic; contact prescriber immediately.
• Reconstitute drug according to label directions with 1.2 ml of sterile water for injection by injecting diluent against side of vial (to prevent excessive foaming).
• Further dilute reconstituted dose with 50 ml of 5% dextrose injection.
• Administer I.V. infusion over 15 minutes.
• Don't use in-line filter.
Adverse reactions
CNS: dizziness, mental status changes, syncope, sensory or motor dysfunction, headache, fatigue, rigors, weakness, malaise, poor memory, depression, sleep disturbances, hallucinations
CV: bradycardia, sinus tachycardia, premature atrial complexes, premature ventricular contractions, arrhythmias, myocardial ischemia, cardiac arrest, capillary leak syndrome and severe hypotension, myocardial infarction EENT: reversible vision changes, conjunctivitis
GI: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain, stomatitis, anorexia, intestinal perforation, ileus, GI bleeding
GU: hematuria, proteinuria, dysuria, renal failure, oliguria or anuria Hematologic: anemia, purpura, eosinophilia, thrombocytopenia, coagulation disorders, leukopenia, leukocytosis
Hepatic: jaundice, ascites
Metabolic: hyperglycemia, hypoglycemia, acidosis, alkalosis
Musculoskeletal: joint and back pain, myalgia
Respiratory: cough, chest pain, tachypnea, wheezing, dyspnea, pulmonary congestion, pulmonary edema, respiratory failure, apnea, pleural effusion
Skin: erythema, pruritus, rash, dry skin, petechiae, urticaria, exfoliative dermatitis
Other: weight gain or loss, fever, chills, edema, infection, pain or reaction at injection site, hypersensitivity reaction
Interactions
Drug-drug. Aminoglycosides, asparaginase, cytotoxic chemotherapy agents, doxorubicin, indomethacin, methotrexate: increased toxicity
Antihypertensives: increased hypotensive effect
Glucocorticoids: reduced antitumor effects
Drug-diagnostic tests. Alkaline phosphatase, bilirubin, glucose, blood urea nitrogen, creatinine, potassium, transaminases: increased levels
Calcium, glucose, magnesium, phosphorus, potassium, protein sodium, uric acid: decreased levels
Patient monitoring
• Monitor heart rate and rhythm, vital signs, and fluid intake and output.
• Assess for signs and symptoms of hypersensitivity reaction and infection.
• Monitor for adverse CNS effects. Report these immediately.
• Evaluate chest X-rays.
• Monitor CBC, electrolyte levels, and liver and kidney function test results.
Patient teaching
See Tell patient that drug lowers resistance to infections. Advise him to immediately report fever, cough, breathing problems, and other signs or symptoms of infection.
See Advise patient to immediately report chest pain, irregular or fast heart beats, easy bruising or bleeding, or abdominal pain.
• Instruct patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Provide dietary counseling. Refer patient to dietitian if adverse GI effects significantly limit food intake.
• Notify patient that he'll undergo blood testing and have chest X-rays taken during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
IL2
A gene on chromosome 4q26-q27 that encodes interleukin-2, a cytokine secreted by T cells in response to antigenic or mitogenic stimulation that plays a central role in the proliferation of T and B lymphocytes. IL-2 upregulates B-cells, monocytes, lymphokine-activated killer cells, natural killer cells and glioma cells.IL-2
Aldesleukin, IL-2, T-cell growth factor Immunology An immunomodulating biological response modifier produced at low baseline levels by CD4 T cells; after antigen presentation by antigen-presenting cells in presence ofIL-1, T cell production of IL-2 and IL-2 receptor–IL-2Rβ on membrane ↑, peaks at 6 hrs and falls to baseline levels; IL-2 is also produced by medullary thymocytes and a subset of large granular lymphocytes–NK cell activators; IL-2 up-regulates the immune system, causing lymphokine-activated killer–LAK cells to lyse tumor cells, see IL-2/LAK cells Therapeutics Recombinant IL-2 has been used for various conditions, including metastatic renal cell CA Adverse effects IL-2 therapy requires wks of intensive care due to toxic effects, including a 'capillary leakage syndrome. ', malaise, gastritis, GI symptoms, anemia, thrombocytopenia, rigors, chills, fever, hypotension, azotemia, jaundice, hyperbilirubinemia, rash–erythroderma globalis, confusion, ascites, fluid retention, pruritus, agitation, respiratory insufficiency, cardiac failure, irreversible demyelinization and hypothyroidism. See IL-2/LAK cells.