PROLEUKIN (aldesleukin) for Injection:

High-Dose Guidelines
Pretherapy interventions Target systolic blood pressure during therapy When to delay or discontinue IL-2

Observation Category* Action

• Discontinue antihypertensive medications. Normal Blood Target Blood
Pressure Pressure Any relative criterion • Initiate corrective measure
• Start acetaminophen, indomethacin, and an H2 and/or delay IL-2.
for the Patient on Therapy
blocker 8-12 hours before administering IL-2. ≥ 3 relative criteria • Initiate corrective measures
and delay IL-2.
• Start maintenance intravenous fluids (ie, lactated <100 mm Hg >80 mm Hg
• Stop IL-2 if adverse events
Ringer’s solution) at 50-100 mL/h immediately are not easily reversed.
before administering IL-2. 100-120 mm Hg >85 mm Hg
Any absolute criterion • Initiate corrective measure
and delay IL-2.
• Premedicate the patient for nausea before
>120 mm Hg >90 mm Hg • Stop IL-2 if adverse event
administering IL-2. is not easily reversed.
Adapted from Schwartzentruber.1 Adapted from Schwartzentruber.1 Adapted from Schwartzentruber.1
*See table below for relative and absolute criteria.

Relative or absolute criteria to be considered when deciding whether to delay or discontinue high-dose IL-2 administration (see table above for decision points)
System Relative Criteria Absolute Criteria
Cardiac • Sinus tachycardia (120-130 bpm) • Sustained sinus tachycardia (if heart rate >130 bpm persists after stopping dopamine and
taking action to correct hypotension, fever, and tachycardia)
• Atrial fibrillation
• Supraventricular tachycardia
• Ventricular arrhythmias (frequent premature ventricular contractions, bigeminy, tachycardia)
• Elevated creatine kinase isoenzymes or troponin
• Electrocardiogram changes indicative of ischemia

Dermatologic – • Moist desquamation

Gastrointestinal • Diarrhea ≥1000 mL/shift • Diarrhea ≥1000 mL/shift on 2 consecutive shifts

• Ileus and/or abdominal distention • Vomiting not responsive to medication
• Bilirubin >7 mg/dL • Severe abdominal distention affecting breathing
• Severe, unrelenting abdominal pain

Hemodynamic • Maximum phenylephrine hydrochloride 1-1.5 µg/kg/min • Maximum phenylephrine hydrochloride 1.5-2 µg/kg/min
• Minimum phenylephrine hydrochloride >0.5 µg/kg/min • Minimum phenylephrine hydrochloride >0.8 µg/kg/min

Hemorrhagic • Frank blood in sputum, emesis, or stool • Guiac-positive sputum, emesis, and/or stool
• Platelet count of 30,000-50,000/mm3 • Platelet count <30,000/mm3

Infection – • Documented or strongly suspected

Musculoskeletal • Extremity tightness • Extremity paresthesias

Neurologic/Psychiatric • Vivid dreams • Hallucinations

• Emotional lability • Persistent crying
• Mental status changes not reversible within 2 hours
• Inability to subtract serial 7s or spell “WORLD” backward (“DLROW”)
• Disorientation

Pulmonary • 3-4 L O2 by nasal cannula to achieve O2 saturation ≥95% • >4 L O2 by nasal cannula to achieve O2 saturation ≥95% or 40% O2 mask to achieve
• Shortness of breath while resting O2 saturation ≥95%
• Rales 1/3 up chest • Endotracheal intubation
• Moist rales 1/2 up chest
• Pleural effusion requiring tap or chest tube while on therapy

Renal • Urine output of 80-160 mL/shift • Urine output <80 mL/shift

• Urine output rate of 10-20 mL/h • Urine output rate <10 mL/h
• Creatinine level of 2.5-2.9 mg/dL • Creatinine level ≥3 mg/dL

Systemic • Weight gain of >15% –

Adapted from Schwartzentruber. 1

Please see accompanying full prescribing information, including boxed warning.

 PROLEUKIN (aldesleukin) for Injection:
®

High-Dose Guidelines (continued)

ICU transfer criteria related to the development Requirements for managing capillary leak
Management of capillary leak syndrome
of capillary leak syndrome (CLS) syndrome in the ICU

Oliguria • Monitor blood pressure before and after IL-2 doses.

• Central venous catheter to monitor central • Assess clinical symptoms of hypotension, dizziness, light-headedness,
• Inability to maintain urine output >20 mL/h with 2 L venous pressure and fainting.
normal saline solution (0.9%) IV boluses • Report persistent hypotension (SBP <90 mm Hg) that does not
respond to 2 L normal saline solution (0.9%) IV boluses, begin
Hypotension • Foley catheter to monitor urine output dopamine and transfer to ICU.
• Auscultate for breath sounds.
• Persistent SBP <90 mm Hg
• Monitor O2 saturation.
• O2 saturation monitor for hypoxia; O2 at • Monitor heart rate; assess with ECG; report significant tachycardia
Cardiac arrhythmias 2-5 L to prevent hypoxemia or arrhythmias.
• ST wave changes • Monitor urine output (strict intake and output recording); Foley
catheter may be needed to monitor hourly output.
• Increasing creatinine phosphokinase
• Dopamine 2-5 µg/kg/min to maintain urine • Monitor daily weight.
• Need to constantly monitor cardiac arrhythmias
output at ≥20 mL/h • Monitor electrolytes, blood urea nitrogen, creatinine, liver enzymes;
• Tachycardia >120 bpm initiate treatment to correct abnormally low levels of magnesium,
phosphorus, and/or potassium.
Somnolence • Dopamine and phenylephrine to maintain • Initiate diuretics when hypotension is controlled and creatinine is stable.
SBP at ≥90 mm Hg • Assist patient in adjusting physical activity to conserve energy.
• Mechanism not understood; may be related to CLS
• Report significant changes to physician.
Adapted from White et al.2 Adapted from White et al.2 Adapted from Seipp.3

Symptom management
Symptom Corrective Measure(s)
Arrhythmia (other than sinus tachycardia) Stop IL-2 (most arrhythmias); correct electrolytes, minerals, anemia, hypoxia
Anemia Transfuse packed red blood cells to achieve hematocrit >28% during IL-2 dosing
Acidosis CO2 <20 mmol/L, give 50 mEq sodium bicarbonate IV; CO2 <18 mmol/L, give 100 mEq sodium bicarbonate IV
Chills Warm blankets at first instance; meperidine IV if chills persist
Creatine kinase elevation Order lab tests for isoenzymes or troponin; administer electrocardiogram; if evidence of myocarditis, stop IL-2 (exercise echocardiogram
required before next cycle of IL-2 to rule out myocardial dysfunction; future IL-2 may be considered if echocardiogram is normal)
Dermatitis Oatmeal baths; nonsteroidal, nonalcoholic lotions
Diarrhea Antidiarrheals (alternate medications); avoid overuse because of complicating ileus and distention
Edema Elevate symptomatic extremity; use fluids judiciously
Epigastric pain Evaluate cause; give indomethacin rectally; consider antacids
Fever breakthrough Increase frequency of indomethacin to every 6 hours; consider septic workup if fever happens after first 24 hours of therapy
(ie, high spike above rising baseline during therapy)
Hypoalbuminemia Observe
Hypocalcemia Maintain above lowest normal value
Hypokalemia Maintain potassium above 3.6 mmol/L
Hypomagnesemia Maintain above lowest normal value
Hypotension Initially fluids; add phenylephrine hydrochloride after 1-1.5 L of fluid boluses
Infection Stop IL-2; treat infection as indicated
Mucositis/stomatitis Frequent oral care; mouthwashes; topical anesthetics; room humidifier
Nausea/vomiting Antiemetics (alternate medications and routes if any one not effective)
Nasal congestion Room humidifier; decongestant (no inhalational steroids)
Oliguria Initially fluids; add dopamine after 1-1.5 L of fluid boluses
Poor venous access Peripherally inserted central catheter (PICC) or central line; antibiotic prophylaxis started when PICC/central line is inserted and continued
until line is removed (remove line as soon as not needed for fluids, vasopressors, replacements, diuretics)
Pruritus Oatmeal baths; nonsteroidal, nonalcoholic lotions; antipruritics
Shortness of breath Check transcutaneous O2 saturation and use O2 if <95%; use fluids judiciously; do not use inhalational steroids
Tachycardia (sinus) Correct fever, hypotension, hypoxia, anemia; consider discontinuation of dopamine if used
Thrombocytopenia Consider transfusion if count <20,000/mm3
Troponin elevation Must stop IL-2; will need exercise echocardiogram before the next cycle of IL-2 to rule out myocardial dysfunction; future IL-2 may be
considered if echocardiogram is normal
Adapted from Schwartzentruber.1

Please see accompanying full prescribing information, including boxed warning.

REFERENCES 1. Schwartzentruber DJ. Guidelines for the safe administration of high-dose interleukin-2. J Immunother. 2001;24:287-293. 2. White RL, Jr, Schwartzentruber DJ, Guleria A, et al. Cardiopulmonary toxicity of treatment with
high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. Cancer. 1994;74:3212-3222. 3. Seipp CA. Guidelines for the safe administration of high-dose interleukin-2: nursing considerations.
Biotherapy: Considerations for Oncology Nurses. 2003;6:11-15.
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