Aldesleukin (Monograph)

Brand name: Proleukin
Drug class: Antineoplastic Agents
- Cytokines
- Biologic Response Modifiers
Chemical name: 125-l-Serine-2-133-Interleukin 2 (human reduced)
Molecular formula: C₆₉₀H₁₁₁₅N₁₇₇O₂₀₃S₆
CAS number: 110942-02-4

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Warning

Use only in patients with normal cardiac and pulmonary function as defined by thallium stress testing and pulmonary function tests.¹ Use with extreme caution in patients with histories of cardiac or pulmonary disease even if thallium stress and pulmonary function test results are normal.¹ (See Toxicity and Adequate Patient Monitoring under Cautions.)

Use in hospital setting under supervision of a qualified clinician experienced in therapy with antineoplastic agents.¹ Use only when an intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine are available in case aldesleukin-induced toxicities develop.¹

Risk of developing capillary leak syndrome (CLS); characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into extravascular space.¹ Results in hypotension and reduced organ perfusion; may be severe or fatal.¹ CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, MI, respiratory insufficiency requiring intubation, GI bleeding or infarction, renal insufficiency, edema, and mental status changes.¹ (See Capillary Leak Syndrome under Cautions.)

Possible impaired neutrophil function (reduced chemotaxis) and increased risk of disseminated infection, including sepsis and bacterial endocarditis.¹ Treat preexisting bacterial infections prior to initiation of therapy.¹ Patients with indwelling central lines are at a higher risk for gram-positive bacterial infections.¹ ⁶ ¹⁵ Prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin associated with a reduced incidence of staphylococcal infections.¹

Withhold administration if moderate-to-severe lethargy or somnolence develops; continued administration may result in coma.¹ (See CNS Effects under Cautions.)

Introduction

Antineoplastic and immunomodulating agent; human interleukin-2 (IL-2) derivative and biosynthetic (recombinant DNA origin) cytokine (i.e., lymphokine).¹ ²

Uses for Aldesleukin

Renal Cell Cancer

Treatment of metastatic renal cell carcinoma in selected patients, alone¹ ²² ¹⁰⁹ ¹¹¹ ¹¹⁶ ¹¹⁷ ¹⁴⁴ or in combination¹ ⁵ ²² with surgery¹⁴⁴ or other drug therapies, such as biologic response modifiers (e.g., interferon alfa), ³⁷ ⁴² ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁹ ⁵³ ¹¹⁵ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²¹ ¹²² ¹²³ ¹²⁴ ¹²⁵ ¹²⁶ ¹³⁶ ¹³⁸ ¹⁶¹ or adoptive immunotherapy (e.g., lymphokine-activated killer [LAK] cells, tumor-infiltrating lymphocytes [TILs]).²⁶ ²⁷ ²⁹ ³⁰ ³¹ ³² ³⁷ ³⁸ ⁴⁷ ⁴⁸ ⁴⁹ ⁵¹ ⁹⁸ ¹⁰⁵ ¹²⁷ ¹²⁸ ¹⁵⁶

There is no generally accepted standard therapy for metastatic renal cell carcinoma.²² ⁵² ⁶⁴ ¹⁰⁹

Despite initial response to aldesleukin, tumor relapse is common, particularly following partial response.¹¹³ Treatment of relapsed disease with the same aldesleukin-based therapy is rarely effective,¹¹³ ¹¹⁴ but some secondary responses observed in patients receiving a different aldesleukin-based regimen.¹¹³

Melanoma

Palliative treatment of metastatic melanoma in selected patients, alone and in combination with other agents¹ ⁵ ⁶⁸ including biologic response modifiers (e.g., interferon alfa),⁴³ ⁵³ ⁵⁵ ⁷⁹ ⁸⁰ ⁸¹ ¹⁷³ adoptive immunotherapy (e.g., LAK cells, TILs),³⁰ ³¹ ⁴⁷ ⁵¹ ⁶⁵ ⁶⁶ ⁷⁰ ⁷¹ ⁷⁴ ⁷⁵ ⁷⁶ ⁷⁸ and/or conventional chemotherapeutic agents (e.g., cisplatin, dacarbazine).⁶⁸ ⁸² ¹⁷¹ ¹⁷²

Although higher response rates with some combination regimens,¹⁵ ⁵² ⁶⁵ ⁶⁸ ⁸⁵ ¹⁰⁰ ¹⁰¹ ¹⁷² ¹⁷⁶ improvement in survival not demonstrated and toxicity often is greater.³⁰ ⁵² ⁶⁵ ⁶⁶ ⁸¹ ¹⁰¹ ¹⁷¹ ¹⁷² ¹⁷⁴ ¹⁷⁵ ¹⁷⁶

Despite initial response to aldesleukin, tumor relapse is common in patients with metastatic melanoma, particularly following partial response.¹¹³ Treatment of relapsed disease with the same aldesleukin-based therapy that produced the initial response rarely is effective,¹¹³ ¹¹⁴ but some secondary responses observed in patients receiving a different aldesleukin-based regimen.¹¹³

Aldesleukin Dosage and Administration

General

To reduce or prevent adverse effects, premedication with antipyretics (including an NSAIA) and histamine H₂-receptor antagonists may be given.¹

Administration

Administer by IV infusion.¹ ³

Also administered by sub-Q injection^{† [off-label]}.¹⁵ ²² ⁴⁰ ⁵⁵

IV Administration

Allow solution to reach room temperature prior to IV infusion.¹

Use plastic (PVC) containers for more consistent delivery; drug may adhere to glass.¹ ⁵²

Do not use an inline filter.¹ ¹⁰¹

Do not coadminister with other drugs in the same container.¹

Consult manufacturer and/or specialized references for instructions on preparation of solutions administered by continuous IV infusion^{† [off-label]} or sub-Q administration^{† [off-label]}.¹⁰¹

Reconstitution

Reconstitute vial containing 22 million units (1.3 mg) of the drug with 1.2 mL of sterile water for injection to provide a solution containing 18 million units (1.1 mg)/mL.¹

Direct sterile water for injection toward the side of the vial with gentle swirling to avoid excessive foaming of the solution; do not shake.¹

Dilution

Add appropriate reconstituted dose to 50 mL of 5% dextrose injection.¹ ¹⁰¹

Solutions outside the range of 30–70 mcg/mL may result in increased variability in drug delivery; avoid use of such solutions for short-duration IV infusions.¹ ¹⁰¹ Manufacturer states that a larger or smaller volume of 5% dextrose injection may be used to maintain a concentration of 30–70 mcg/mL.¹ ¹⁰¹

Rate of Administration

Administer over 15 minutes.¹ ¹⁰¹

Dosage

Potency usually is expressed in international units (IU);¹ ³ because other units also have been reported (e.g., Cetus Units [CU], Roche Units [RU], Biologic Response Modifiers Program Units [BRMPU]) and are not equivalent (e.g., 1 RU = 3 IU, 1 CU = 6 IU), exercise care in interpreting published dosages and concentrations.³ ¹⁰¹

International units are stated as units rather than as IU to minimize medication errors that could result from misinterpretation of written orders employing IU.^b

When a vial containing 22 million units is reconstituted by adding 1.2 mL of sterile water for injection, each mL contains 18 million units of aldesleukin (equivalent to 1.1 mg of drug).¹

Optimum dosage and regimen for treatment of metastatic renal cell carcinoma¹⁵ ³¹ ³⁴ ³⁹ ⁴⁰ ⁴⁹ ⁵² ⁵⁴ ⁵⁵ ⁹⁹ ¹⁰¹ ¹⁰³ ¹¹¹ ¹¹⁶ ¹⁴³ or metastatic melanoma not established.¹⁵ ⁵² ⁶⁶ ¹⁰¹ ¹⁷⁰

Administration of doses in excess of recommended dose associated with a more rapid onset of anticipated dose-limiting toxicities.¹

Tumor regression has continued for up to 12 months after 1 or more courses of therapy, but optimum duration of therapy not yet established.¹ ³

Consult manufacturer and/or specialized references for instructions on alternative dosages administered by continuous IV infusion^{† [off-label]} or sub-q injection^{† [off-label]}.¹⁰¹

Adults

Renal Cell Cancer

Intermittent IV Infusion

600,000 units/kg over 15 minutes every 8 hours for 14 doses (5-day treatment cycle), followed by a 9-day rest period, and a second 5-day treatment cycle (600,000 units/kg over 15 minutes every 8 hours for 14 doses) for a maximum of 28 doses or until intolerable adverse effects develop.¹ ²³ ³⁸ ⁵² ¹¹¹ (See Dosage Modification for Toxicity and Contraindications for Retreatment under Dosage and Administration.)

Alternatively, some clinicians have used 720,000 units/kg over 15 minutes every 8 hours for a maximum of 15 doses per cycle, with a 10-day rest period between the 2 cycles.²⁰ ³¹

Manufacturer recommends drug-free interval ≥7 weeks between treatment courses from date of previous hospital discharge;¹ however, some clinicians report using shorter rest periods (i.e., 2–4 weeks) between courses.⁵²

Evaluate patients approximately 4 weeks after completion of initial course of therapy and again immediately prior to scheduled start of next course.¹ Manufacturer states that further therapy with aldesleukin should be undertaken only if there is evidence of tumor regression following the last course and the patient has not developed serious toxicity that would contraindicate continuation.¹ Some clinicians believe stabilization of disease in absence of serious toxicity warrants continued therapy.⁵² ¹⁰¹

Continuous IV Infusion†

18 million units/m² daily for two 5-day cycles, with a drug-free interval of 5–8 days between cycles.¹⁵ ³² ³⁵ ³⁶ ³⁷ ³⁸ ⁹⁷ ¹¹⁵ ¹¹⁹

Sub-Q Injection†

18 million units daily for 5 days followed by a 2-day rest period.¹⁵ ⁴⁰ For additional cycles, 9 million units on days 1 and 2, followed by 18 million units daily for the next 3 days.¹⁵ ⁴⁰ ⁵² ¹⁰¹ Treatment cycles of 6 consecutive weeks separated by a 3-week drug-free period were used.⁴⁰

Melanoma

IV Infusion

600,000 units/kg over 15 minutes every 8 hours for 14 doses (5-day treatment cycle), followed by a 6- to 9-day rest period, then a second 5-day treatment cycle (600,000 units/kg over 15 minutes every 8 hours for 14 doses) for a maximum of 28 doses per course or until intolerable adverse effects develop.¹ ¹⁷⁰

Alternatively, some clinicians have used 720,000 units/kg over 15 minutes every 8 hours for a maximum of 15 doses per cycle, with a 10-day rest period between the 2 cycles.²⁰ ³¹

Manufacturer recommends drug-free interval ≥7 weeks between treatment courses from date of previous hospital discharge;¹ however, some clinicians report using rest periods of 6–12 weeks between courses.¹⁷⁰

Dosage Modification for Toxicity and Contraindications for Retreatment

Contraindications for Retreatment1 52

Retreatment is contraindicated in patients who have experienced the following toxicities:¹

Cardiovascular:

Sustained ventricular tachycardia (≥5 beats)

Cardiac rhythm disturbances, not controlled or unresponsive to management

Chest pain with ECG changes, consistent with angina or MI

GI:

Bowel ischemia/perforation

GI bleeding requiring surgery

Neurologic:

Coma or toxic psychosis lasting >48 hours

Repetitive or difficult-to-control seizures

Cardiac tamponade

Respiratory:

Intubation for >72 hours

Renal:

Renal failure requiring dialysis for >72 hours

Therapy Interruptions for Toxicity

Toxicities requiring dosage modification should involve withholding or interrupting a dose rather than reducing the individual dose to be given.¹

Therapy Interruptions for Toxicity Based on Manifestations
Toxicity	Hold dose for:	May give subsequent dose if:
Cardiovascular	Atrial fibrillation, supraventricular tachycardia, recurrent or persistent bradycardia or bradycardia requiring treatment¹	Asymptomatic with complete recovery to normal sinus rhythm¹
	SBP <90 mm Hg with increasing vasopressor requirements¹	SBP ≥90 mm Hg and stable or improving vasopressor requirement ¹
	ECG changes consistent with MI, ischemia, or myocarditis, with or without chest pain, or suspicion of cardiac ischemia¹	Asymptomatic; MI and myocarditis ruled out; minimal clinical suspicion of angina; or no evidence of ventricular hypokinesia¹
Dermatologic	Bullous dermatitis or marked worsening of preexisting skin condition; avoid topical corticosteroid therapy¹	All signs of bullous dermatitis resolved¹
GI	GI bleeding demonstrated by stool guaiac test repeatedly positive with a result >3+ or 4+¹	Negative stool guaiac test results¹
Hepatic	Signs of hepatic failure, including encephalopathy, increasing ascites, liver pain, or hypoglycemia¹	When all signs of hepatic failure have resolved; initiate a new course of treatment (if warranted) ≥7 weeks after cessation of adverse events and hospital discharge¹
Infectious complications	Sepsis syndrome occurs and patient is clinically unstable¹	Sepsis syndrome resolved, patient is clinically stable and infection is being treated¹
Neurologic	Changes in mental status (e.g., moderate confusion, agitation)¹	Mental status changes completely resolved¹
Renal	S_cr ≥4.5 mg/dL or ≥4 mg/dL in presence of severe volume overload, acidosis, or hyperkalemia¹	S_cr <4 mg/dL and stable fluid and electrolyte status¹
	Persistent oliguria with urine output <10 mL/hour for 16–24 hours with increasing S_cr¹	Urine output >10 mL/hour with a decrease in S_cr of >1.5 mg/dL or normalization of S_cr¹
Respiratory	Oxygen saturation <90%¹	Oxygen saturation ≥90%¹

Prescribing Limits

Adults

Renal Cell Carcinoma or Melanoma

IV Infusion

Maximum 28 doses per course.¹

Special Populations

No special population dosage recommendations at this time.¹ Manufacturer states patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy.¹ (See Patient Selection, CNS Effects, Hepatic Impairment, Renal Impairment, and Geriatric Use, all under Cautions.)

Cautions for Aldesleukin

Contraindications

Known history of hypersensitivity to IL-2 or any ingredient in the formulation.¹
Abnormal thallium stress test results.¹
Abnormal pulmonary function test results.¹
Organ allografts.¹
Further therapy contraindicated if certain toxicities developed during previous aldesleukin therapy (i.e., sustained ventricular tachycardia [≥5 beats], uncontrolled cardiac arrhythmias or arrhythmias unresponsive to management, chest pain with ECG changes consistent with angina or MI, cardiac tamponade, intubation for >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, or GI bleeding requiring surgery).¹ (See Dosage Modification for Toxicity and Contraindications for Retreatment under Dosage and Administration.)

Warnings/Precautions

Warnings

Patient Selection

Careful patient selection mandatory prior to initiation of drug, including assessment of cardiac, renal, hepatic, CNS, and pulmonary functions, blood chemistry, and blood cell counts.¹ (See Boxed Warning and also see Toxicity and Adequate Patient Monitoring under Cautions.)

However, even patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience adverse events.¹ Adverse effects are frequent, often serious, and sometimes fatal.¹ ⁶ ¹⁵ ²⁰ Carefully weigh risks versus benefits of therapy.¹ ¹⁵ ⁶ ²⁰ (See Contraindications under Cautions.)

Patients with favorable Eastern Cooperative Oncology Group performance status (ECOG PS 0) at treatment initiation have a higher response rate and lower toxicity; therefore, consider performance status during patient selection for treatment.¹ ¹¹¹ ¹¹² Experience in patients with ECOG PS >1 extremely limited.¹

Autoimmune and Inflammatory Reactions

Possible development or exacerbation of autoimmune disease and inflammatory disorders when used alone or in combination with interferon alfa.¹ (See Specific Drugs under Interactions.)

Possible onset of symptomatic hyperglycemia and/or diabetes mellitus.¹

Possible hypothyroidism, sometimes preceded by hyperthyroidism, following treatment; may require thyroid hormone replacement therapy.¹ Hyperthyroidism also reported.¹

Increased risk of allograft rejection in transplant patients because of enhanced cellular immune function.¹

Exacerbation of Crohn’s disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, and bullous pemphigoid reported.¹

CNS Effects

Thoroughly evaluate and treat all patients for CNS metastases; must have a negative CT scan prior to receiving therapy.¹

New neurologic manifestations (e.g., mental status changes, speech difficulties, cortical blindness, limb/gait ataxia, hallucinations, agitation, obtundation, coma) and anatomic lesions reported following aldesleukin therapy in patients without evidence of CNS metastases.¹ ⁶ ⁸ ⁹ ¹⁵ ²⁰

Mental status changes (e.g., irritability, confusion, depression, agitation, lethargy, somnolence) may be a direct result of CNS toxicity from aldesleukin or indicative of bacteremia, early bacterial sepsis, hypoperfusion, or occult CNS malignancy.¹ Aldesleukin-induced mental status changes generally reverse within several days after discontinuance of the drug,¹⁵ although may progress for several days before recovery begins.¹ ¹⁵ ¹⁰¹ However, permanent neurologic defects reported.¹

Potential for seizures; use with extreme caution if known seizure disorders.¹

Sensitivity Reactions

Risk of anaphylaxis in patients receiving various treatment regimens that included aldesleukin.¹

Hypersensitivity reactions (e.g., erythema, pruritus, hypotension) reported within hours of administration of therapy in patients receiving combination regimens with sequential administration of high-dose aldesleukin and antineoplastic agents (specifically cisplatin, dacarbazine, tamoxifen, and interferon alfa);¹ medical intervention required in some patients.¹ (See Specific Drugs under Interactions.)

Potential for nonanaphylactic allergic reactions.¹⁴⁰

May predispose individuals to acute, atypical adverse reactions to iodinated radiographic contrast media.¹ (See Specific Drugs under Interactions.)

Major Toxicities

Capillary Leak Syndrome

Risk of CLS particularly at usual dosages recommended by the manufacturer; risk of severe, possibly fatal, hypotension and reduced organ perfusion.¹ ⁶ ⁸ ¹¹ ¹⁵ ¹⁰¹ Begins immediately after treatment initiation; characterized by increased vascular permeability to proteins and fluids and reduced vascular tone.¹ ⁶ ¹⁵ (See Boxed Warning.)

Monitor fluid and organ perfusion status carefully; frequently monitor BP, heart rate, and organ function, including assessment of mental status and urine output.¹ Assess hypovolemia by catheterization and central venous pressure monitoring.¹

If hypovolemia occurs, administration of IV fluids (e.g., colloid replacement fluids or crystalloids) recommended.¹ Use caution when administering large volumes of IV fluids to correct hypovolemia; unrestrained fluid administration may exacerbate complications associated with edema or effusions.¹

Use extreme caution when treating patients with fixed requirements for large volumes of fluid (e.g., those with hypercalcemia); flexibility in fluid and vasopressor management is essential for maintaining organ perfusion and BP.¹ ¹⁰¹

Management of edema and ascites and/or effusions depends on careful balancing of fluid shifts to ensure that the consequences of hypovolemia (e.g., impaired organ perfusion) or fluid accumulation (e.g., pulmonary edema) do not exceed the patient’s tolerance.¹

Early administration of IV dopamine with or without IV phenylephrine hydrochloride before onset of hypotension can help maintain organ perfusion, particularly renal perfusion, and preserve urine output.¹ Exercise caution; prolonged use of vasopressors, alone or in combination, at relatively high doses may be associated with cardiac rhythm disturbances.¹

If adequate organ perfusion not maintained (demonstrated by altered mental status, reduced urine output, decrease in SBP to <90 mm Hg, or onset of cardiac arrhythmias), withhold subsequent aldesleukin doses until organ perfusion recovers and SBP ≥90 mm Hg.¹

Recovery from CLS begins within a few hours after discontinuance of aldesleukin therapy.¹ If excessive weight gain, edema or pulmonary congestion with shortness of breath occurs, diuretics may hasten recovery once BP normalized.¹

Flu-like Syndrome

Flu-like syndrome (e.g., fever [sometimes grade 4 or life-threatening], chills, rigors) possible.¹ ⁶ ¹³ ¹⁵ Other symptoms possible (e.g., pain,¹ abdominal pain,¹ malaise,¹ asthenia, ¹ arthralgia and/or myalgia, ¹⁵ ¹⁴⁰ chest pain,¹⁴⁰ back pain,¹⁴⁰ fatigue).¹⁴⁰

General Precautions

Toxicity and Adequate Patient Monitoring

Highly toxic drug; prior to initiation of therapy and daily during therapy, perform hematologic tests (e.g., CBC, differential, platelet counts), blood chemistries (e.g., serum electrolyte concentrations), renal and hepatic function tests, and chest radiographs.¹ (See Cardiovascular Effects, Pulmonary Effects, Renal Impairment, and Hepatic Impairment, all under Cautions.)

During therapy, monitor vital signs (i.e., temperature, pulse, BP, respiration rate) at least every 4 hours⁵² and patient’s weight and fluid intake and output daily.¹ ⁵² In hypotensive patients, monitor vital signs hourly.¹ If SBP decreases (especially to <90 mm Hg), perform constant cardiac rhythm monitoring.¹ (See Cardiovascular Effects under Cautions.)

Cardiovascular Effects

Prior to initiation of therapy, perform a stress thallium study to document normal cardiac ejection fraction and unimpaired myocardial wall motion.¹ ¹⁰¹ If results suggest minor wall motion abnormalities, test further to exclude CAD.¹ (See Boxed Warning.)

During therapy, assess cardiac function daily.¹ If signs or symptoms (e.g., chest pain, murmurs, gallops, irregular cardiac rhythm, palpitation), assess with an ECG and cardiac enzymes.¹ Evidence of myocardial injury, including findings compatible with MI or myocarditis, reported.¹ Ventricular hypokinesia caused by myocarditis may persist for several months.¹ If evidence of cardiac ischemia or CHF, withhold therapy and repeat thallium study.¹

Pulmonary Effects

Perform baseline pulmonary function tests with arterial blood gases in all patients.¹ Must have adequate pulmonary function (FEV₁ >2 L or >75% of predicted value based on height and age) prior to initiation of therapy.¹

Monitor pulmonary function regularly during therapy.¹ If dyspnea or clinical signs of respiratory impairment (i.e., tachypnea or rales), assess with arterial blood gases.¹ Repeat as often as clinically indicated.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether aldesleukin is distributed into milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

Response, median number of doses per course, and median number of courses of therapy in patients ≥65 years of age does not appear to differ from that in younger adults; however, possible increased risk of toxicity in patients with renal impairment.¹ Possible increased incidence of severe urogenital toxicity and dyspnea compared with younger patients.¹

Hepatic Impairment

Aldesleukin therapy impairs hepatic function.¹ Normal hepatic function necessary at start of therapy.¹ (See Toxicity and Adequate Patient Monitoring under Cautions and also see Hepatotoxic Agents under Interactions.)

Renal Impairment

Contraindicated in patients who develop renal impairment requiring dialysis for >72 hours after a previous course of aldesleukin.¹

Aldesleukin therapy impairs renal function.¹ Preexisting renal impairment appears to be associated with an increased risk of more severe and prolonged renal dysfunction.¹⁰ ¹⁵ (See Toxicity and Adequate Patient Monitoring under Cautions and also see Nephrotoxic Agents under Interactions.)

Manufacturer states that S_cr should be≤1.5 mg/dL prior to initiation of aldesleukin therapy.¹

Common Adverse Effects

Hypotension, diarrhea, renal dysfunction with oliguria, chills, vomiting, dyspnea, rash, bilirubinemia, thrombocytopenia, nausea, confusion, increased S_cr, anemia, fever, peripheral edema, malaise, lung disorders (e.g., pulmonary congestion, rales, rhonchi), pruritus, asthenia, tachycardia, increased AST, stomatitis, somnolence, anorexia.¹

Life-threatening or grade 4 adverse effects: Renal dysfunction with oliguria/anuria, hypotension, respiratory disorder (i.e., ARDS, respiratory failure, intubation), coma, bilirubinemia.¹

Drug Interactions

Cardiotoxic Agents

Concurrent administration may increase risk of cardiotoxicity.¹

CNS-Active Agents

Concurrent administration may increase risk of CNS effects.¹

Hepatotoxic Agents

Concurrent administration may increase risk of hepatotoxicity. (See Hepatic Impairment under Cautions.)¹

Myelotoxic Agents

Concurrent administration may increase risk of myelotoxicity.¹

Nephrotoxic Agents

Concurrent administration may increase risk of nephrotoxicity. (See Renal Impairment under Cautions.)¹

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	Possible increase in nephrotoxicity¹
Anthracyclines (e.g., doxorubicin)	Possible increase in cardiotoxicity¹
Antihypertensive agents (e.g., β-blocking agents)	Possible increase in hypotensive effects¹
Antineoplastic agents	Possible increased myelotoxicity¹	Safety and efficacy not established¹
Asparaginase	Possible increase in hepatotoxicity¹
Cisplatin	Potential hypersensitivity reactions (erythema, pruritus, and hypotension)¹	Medical intervention may be required¹
CNS depressants (e.g., analgesics, antiemetics, opiate agonists, sedatives, tranquilizers)	Possible increased risk of CNS effects¹
Corticosteroids (glucocorticoids)	Possible reduction of antitumor effectiveness¹	Avoid concomitant use¹
Dacarbazine	Potential hypersensitivity reactions (erythema, pruritus, and hypotension)¹	Medical intervention may be required¹
Indomethacin	Possible increase in nephrotoxicity¹
Interferon alfa	Possible development or exacerbation of autoimmune disease and inflammatory disorders (e.g., thyroiditis,¹ inflammatory arthritis,¹ oculo-bulbar myasthenia gravis,¹ crescentic IgA glomerulonephritis,¹ ¹⁵⁵ Stevens-Johnson syndrome,¹ or bullous pemphigoid)¹ Possible increased incidence of myocardial injury (MI,¹ myocarditis,¹ ventricular hypokinesia,¹ and severe rhabdomyolysis)¹ Potential hypersensitivity reactions (erythema, pruritus, and hypotension)¹	Medical intervention may be required¹
Methotrexate	Possible increase in hepatotoxicity¹
Roentgenographic agents	Potential acute, atypical adverse reactions (e.g., fever, chills, nausea, vomiting, diarrhea, pruritus, rash, hypotension, edema, oliguria)¹ to iodinated radiographic contrast media ¹	May occur when contrast media are administered up to several months after aldesleukin administration¹
Tamoxifen	Potential hypersensitivity reactions (erythema, pruritus, and hypotension)¹	Medical intervention may be required¹

Aldesleukin Pharmacokinetics

Absorption

Bioavailability

Approximately 30% of a dose detectable in plasma upon completion of IV infusion.¹

Distribution

Extent

Rapidly distributed into extravascular space; animal studies indicate rapid (<1 minute) uptake into lung, liver, kidney, and spleen.¹

Not known whether aldesleukin is distributed into milk.¹

Elimination

Metabolism

Metabolized principally in the kidney.¹

Elimination Route

Excreted in urine; little or no active drug detected.¹

Half-life

85 minutes.¹

Stability

Storage

Parenteral

Powder for Injection

Store in carton at 2–8°C until used; protect from light.¹

Preferably, store reconstituted or diluted solution at 2–8°C.¹ Alternatively, store at room temperature for ≤48 hours.¹ Do not freeze.¹

Actions

Biologic response modifier; possesses biologic activities of IL-2.¹
Precise mechanism of action unknown; whether effects on immune system contribute to antineoplastic activity not established.¹
Exerts a wide range of regulatory actions on the immune system in vitro, including enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human IL-2 dependent cell lines, enhancement of lymphocyte cytotoxicity, induction of LAK cell and natural killer (NK) cell activity, and induction of interferon-gamma production.¹
Produces immune effects in a dose-dependent manner.¹ Activates cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia; stimulates production of cytokines (e.g., tumor necrosis factor, IL-1, interferon gamma).¹

Advice to Patients

Risk of serious, life-threatening, or fatal adverse effects in patients with normal cardiovascular, pulmonary, hepatic, or CNS function.¹
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular or pulmonary disease).¹
Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Aldesleukin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion	22 million units	Proleukin	Novartis

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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