Look Up > Drugs > Aldesleukin
Aldesleukin
Pronunciation
U.S. Brand Names
Generic Available
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Monitoring Parameters
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(al des LOO kin)

U.S. Brand Names
Proleukin®

Generic Available

No


Synonyms
IL-2; Interleukin-2

Pharmacological Index

Biological Response Modulator


Use

Treatment of metastatic renal cell carcinoma; also, investigated in tumors known to have a response to immunotherapy, such as melanoma; has been used in conjunction with LAK cells, TIL cells, IL-1, and interferon


Pregnancy Risk Factor

C


Contraindications

Known history of hypersensitivity to interleukin-2 or any component; patients with an abnormal thallium stress test or pulmonary function test; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia ( greater than or equal to 5 beats), cardiac rhythm disturbances not controlled or unresponsive to management, recurrent chest pain with EKG changes (consistent with angina or myocardial infarction), intubation required >72 hours, pericardial tamponade; renal dysfunction requiring dialysis >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, GI bleeding requiring surgery


Warnings/Precautions

High-dose IL-2 therapy has been associated with capillary leak syndrome (CLS); CLS results in hypotension and reduced organ perfusion which may be severe and can result in death; therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing; extreme caution should be used in patients with normal thallium stress tests and pulmonary functions tests who have a history of prior cardiac or pulmonary disease. Postnephrectomy patients must have a serum creatinine of less than or equal to 1.5 mg/dL prior to treatment.

Standard prophylactic supportive care during high-dose IL-2 treatment includes acetaminophen to relieve constitutional symptoms and an H2-antagonist to reduce the risk of GI ulceration and/or bleeding.


Adverse Reactions

>10%:

Cardiovascular: Sensory dysfunction, sinus tachycardia, arrhythmias, pulmonary congestion; hypotension (dose-limiting toxicity) which may require vasopressor support and hemodynamic changes resembling those seen in septic shock can be seen within 2 hours of administration; angina, acute myocardial infarction, SVT with hypotension has been reported, edema

Central nervous system: Dizziness, pain, fever, chills, cognitive changes, fatigue, malaise, disorientation, somnolence, paranoid delusion, and other behavioral changes; reversible and dose related; however, may continue to worsen for several days even after the infusion is stopped

Dermatologic: Pruritus, erythema, rash, dry skin, exfoliative dermatitis, macular erythema

Gastrointestinal: Nausea, vomiting, weight gain, diarrhea, stomatitis, anorexia, GI bleeding

Hematologic: Anemia, thrombocytopenia, leukopenia, eosinophilia, coagulation disorders

Hepatic: Elevated transaminase and alkaline phosphatase, jaundice

Neuromuscular & skeletal: Weakness, rigors which can be decreased or ameliorated with acetaminophen or a nonsteroidal agent and meperidine

Renal: Oliguria, anuria, proteinuria; renal failure (dose-limiting toxicity) manifested as oliguria noted within 24-48 hours of initiation of therapy; marked fluid retention, azotemia, and increased serum creatinine seen, which may return to baseline within 7 days of discontinuation of therapy; hypophosphatemia

Respiratory: Dyspnea, pulmonary edema

1% to 10%: Cardiovascular: Increase in vascular permeability: Capillary-leak syndrome manifested by severe peripheral edema, ascites, pulmonary infiltration, and pleural effusion; occurs in 2% to 4% of patients and is resolved after therapy ends

<1%: Congestive heart failure, coma, seizure, alopecia, hypercalcemia, hypocalcemia, hypomagnesemia, hypothyroidism, increased plasma levels of stress-related hormones, acidosis, pancreatitis, polyuria, arthritis, muscle spasm, allergic reactions


Overdosage/Toxicology

Side effects following the use of aldesleukin are dose related. Administration of more than the recommended dose has been associated with a more rapid onset of expected dose-limiting toxicities. Adverse reactions generally will reverse when the drug is stopped particularly because of its short serum half-life.

Provide supportive treatment of any continuing symptoms. Life-threatening toxicities have been ameliorated by the I.V. administration of dexamethasone, which may result in less of therapeutic effect of aldesleukin.


Drug Interactions

Decreased toxicity: Corticosteroids have been shown to decrease toxicity of IL-2, but have not been used since there is concern that they may decrease the efficacy of the lymphokine

Increased toxicity:

Aldesleukin may affect central nervous function; therefore, interactions could occur following concomitant administration of psychotropic drugs (eg, narcotics, analgesics, antiemetics, sedatives, tranquilizers)

Concomitant administration of drugs possessing nephrotoxic (eg, aminoglycosides, indomethacin), myelotoxic (eg, cytotoxic chemotherapy), cardiotoxic (eg, doxorubicin), or hepatotoxic (eg, methotrexate, asparaginase) effects with aldesleukin may toxicity in these organ systems; the safety and efficacy of aldesleukin in combination with chemotherapy agents has not been established

Beta-blockers and other antihypertensives may potentiate the hypotension seen with Proleukin®

Iodinated contrast media: Acute reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria have occurred within hours of contrast infusion; this reaction may occur within 4 weeks or up to several months after IL-2 administration


Stability

Store vials of lyophilized injection in a refrigerator at 2°C to 8°C (36°F to 46°F)

Reconstituted or diluted solution is stable for up to 48 hours at refrigerated and room temperatures 2°C to 25°C (36°F to 77°F); however, since this product contains no preservatives, the reconstituted and diluted solutions should be stored in the refrigerator

Compatible only with D5W

Gently swirl, do not shake

Note: As with most biological proteins, solutions containing IL-2 should not be filtered; filtration will result in significant loss of bioactivity

Standard aldesleukin I.V. dilutions:

Dose/50-1000 mL D5W

Concentrations <1,000,000 units/mL require the addition of human albumin to PVC bag prior to addition of IL-2

Stable for 48 hours at room temperature or refrigeration (2°C to 8°C); refrigeration is recommended due to lack of preservative

Incompatible with NS

Recommendations for IL-2 (Aldesleukin - Proleukin™) dilutions in D5 W*

  • Concentrations of <60 mcg/mL (<1 million units/mL), human serum albumin must be added to bag prior to addition of IL-2. These solutions are stable for 6 days at room temperature.**
  • Concentrations of 60-100 mcg/mL (1-1.7 million units/mL) should not be utilized as they are unstable.
  • Concentrations of 100-500 mcg/mL (1.7-8.4 million units/mL) are stable for 6 days at room temperature.**

*1.3 mg of IL-2 (aldesleukin - Proleukin™) is equivalent to 22 million units.

**Although stability is 6 days, IL-2 does not contain a preservative and 24-hour expiration dating should be used.

Concentrations of IL-2 which fall into the unstable (60-100 mcg/mL or 1-1.7 microunits/mL) range require addition of human serum albumin (final human serum albumin concentration of 0.1%). Volume of human serum albumin to be added to IL-2 (aldesleukin - Proleukin™) infusions in D5 W:

Volume of I.V. diluent 50 mL:

Add 1 mL 5% human serum albumin or 0.2 mL 25% human serum albumin

Volume of I.V. diluent 100 mL:

Add 2 mL 5% human serum albumin or 0.4 mL 25% human serum albumin

Volume of I.V. diluent 150 mL:

Add 3 mL 5% human serum albumin or 0.6 mL 25% human serum albumin

Volume of I.V. diluent 200 mL:

Add 4 mL 5% human serum albumin or 0.8 mL 25% human serum albumin

Volume of I.V. diluent 250 mL:

Add 5 mL 5% human serum albumin or 1 mL 25% human serum albumin

Volume of I.V. diluent 500 mL:

Add 10 mL 5% human serum albumin or 2 mL 25% human serum albumin


Mechanism of Action

IL-2 promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; IL-2 also causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; IL-2 can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells. LAK cells (which are derived from lymphocytes from a patient and incubated in IL-2) have the ability to lyse cells which are resistant to NK cells; TIL cells (which are derived from cancerous tissue from a patient and incubated in IL-2) have been shown to be 50% more effective than LAK cells in experimental studies.


Pharmacodynamics/Kinetics

Absorption: Oral: Not absorbed

Distribution: Vd: Has been noted to be 4-7 L; primarily into the plasma and then into a second compartment, the lymphocytes themselves

Bioavailability: I.M.: 37%

Half-life: Initial: 6-13 minutes; Terminal: 20-120 minutes


Usual Dosage

Refer to individual protocols; all orders must be written in million International units (million IU)

Treatment consists of two 5-day treatment cycles separated by a rest period. 600,000 units/kg (0.037 mg/kg)/dose administered every 8 hours by a 15-minute I.V. infusion for a total of 14 doses; following 9 days of rest, the schedule is repeated for another 14 doses, for a maximum of 28 doses per course

Dose modification: In high-dose therapy of RCC, see manufacturer's guidelines for holding and restarting therapy; hold or interrupt a dose - DO NOT DOSE REDUCE; or refer to specific protocol

Retreatment: Patients should be evaluated for response approximately 4 weeks after completion of a course of therapy and again immediately prior to the scheduled start of the next treatment course; additional courses of treatment may be given to patients only if there is some tumor shrinkage or stable disease following the last course and retreatment is not contraindicated. Each treatment course should be separated by a rest period of at least 7 weeks from the date of hospital discharge; tumors have continued to regress up to 12 months following the initiation of therapy

Investigational regimen: S.C.: 11 million Units (flat dose) daily x 4 days per week for 4 consecutive weeks; repeat every 6 weeks


Monitoring Parameters

The following clinical evaluations are recommended for all patients prior to beginning treatment and then daily during drug administration:

Standard hematologic tests including CBC, differential, and platelet counts

Blood chemistries including electrolytes, renal and hepatic function tests

Chest x-rays

Daily monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, constant cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an EKG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked.

During treatment, pulmonary function should be monitored on a regular basis by clinical examination, assessment of vital signs and pulse oximetry. Patients with dyspnea or clinical signs of respiratory impairment (tachypnea or rales) should be further assessed with arterial blood gas determination. These tests are to be repeated as often as clinically indicated.

Cardiac function is assessed daily by clinical examination and assessment of vital signs. Patients with signs or symptoms of chest pain, murmurs, gallops, irregular rhythm or palpitations should be further assessed with an EKG examination and CPK evaluation. If there is evidence of cardiac ischemia or congestive heart failure, a repeat thallium study should be done.


Mental Health: Effects on Mental Status

Sedation, disorientation, delusions, and cognitive changes are common, reversible, and dose related


Mental Health: Effects on Psychiatric Treatment

Propranolol potentiates hypotensive effects. Interaction may occur with other psychotropic given aldesleukin's effect on mental status.


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

Stomatitis in >10% of patients


Patient Information

This drug can only be administered by infusion. Avoid alcohol and all OTC or prescription drugs unless approved by your oncologist. You will be sensitive to sunlight; use of sunblock (15 SPF or greater), wear protective clothing, or avoid direct sun exposure. You will be susceptible to infection; avoid crowds or infected persons or persons with contagious diseases. Frequent mouth care and small frequent meals may help counteract any GI effects you may experience and will help maintain adequate nutrition and fluid intake. This drug may result in many side effects; you will be monitored and assessed closely during therapy, however, it is important that you report any changes or problems for evaluation. Report any changes in urination, unusual bruising or bleeding, chest pain or palpitations, acute dizziness, respiratory difficulty, fever or chills, changes in cognition, rash, feelings of pain or numbness in extremities, severe GI upset or diarrhea, vaginal discharge or mouth sores, yellowing of eyes or skin, or any changes in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not breast-feed.


Nursing Implications

Prior to treatment: Standard hematologic tests, blood chemistries, chest x-rays

During treatment: Pulmonary function, assessment of vital signs and pulse oximetry. Patients with dyspnea or clinical signs of respiratory impairment: Arterial blood gas determination


Dosage Forms

Powder for injection, lyophilized: 22 x 106 international units [18 million international units/mL = 1.1 mg/mL when reconstituted]


References

Foa R, "Interleukin 2 in the Management of Acute Leukaemia," Br J Haematol, 1996, 92(1):1-8.

Kintzel PE and Calis KA, "Recombinant Interleukin-2: Biological Response Modifier," Clin Pharm, 1991, 10(2):110-28.

Lotz MT and Rosenberg SA, "Interleukin-2: Clinical Applications in Biologic Therapy of Cancer," DeVita VT, Hellman S, Rosenberg, eds, J.B. Lippincott Company: Philadelphia, PA, 1991, 159-77.

Lotze MT, "Interleukin-2: Basic Principles in Biologic Therapy of Cancer," DeVita VT, Hellman S, Rosenberg, eds, J.B. Lippincott Company: Philadelphia, PA, 1991, 123-41.

Mule JJ, "Interleukin-2: Preclinical Trials in Biologic Therapy of Cancer," DeVita VT, Hellman S, Rosenberg, eds, J.B. Lippincott Company: Philadelphia, PA, 1991, 142-58.

Whittington R and Faulds D, "Interleukin-2: A Review of Its Pharmacological Properties and Therapeutic Use in Patients With Cancer," Drugs, 1993, 46(3):446-514.

Yang JC, Topalian SL, Parkinson D, et al, "Randomized Comparison of High-Dose and Low-Dose Intravenous Interleukin-2 for the Therapy of Metastatic Renal Cell Carcinoma: An Interim Report," J Clin Oncol, 1994, 12(8):1572-6.


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