INDICATIONS AND USAGE
Proleukin® (aldesleukin) is indicated for the treatment of adults with
metastatic renal cell carcinoma (metastatic RCC).
Proleukin is indicated for the
treatment of adults with metastatic melanoma.
Careful patient selection is mandatory
prior to the administration of Proleukin.
Evaluation of clinical studies to date reveals that patients with more favorable ECOG
performance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with a
higher response rate and lower toxicity. Therefore, selection of patients for treatment
should include assessment of performance status.
Experience in patients with ECOG
PS > 1 is extremely limited.
Proleukin® (aldesleukin) is contraindicated in patients with a known
history of hypersensitivity to interleukin-2 or any component of the Proleukin formulation.
Proleukin is contraindicated in patients with an abnormal thallium stress test or abnormal
pulmonary function tests and those with organ allografts. Retreatment with Proleukin is
contraindicated in patients who have experienced the following drug-related toxicities
while receiving an earlier course of therapy: sustained ventricular tachycardia (≥ 5 beats),
cardiac arrhythmias not controlled or unresponsive to management, chest pain with ECG changes,
consistent with angina or myocardial infarction, cardiac tamponade, intubation for > 72 hours,
renal failure requiring dialysis > 72 hours, coma or toxic psychosis lasting > 48 hours,
repetitive or difficult to control seizures, bowel ischemia/perforation, GI bleeding requiring
Because of the severe adverse events which generally accompany
Proleukin® (aldesleukin) therapy at the recommended dosages, thorough clinical
evaluation should be performed to identify patients with significant cardiac, pulmonary, renal,
hepatic, or CNS impairment in whom Proleukin is contraindicated. Patients with normal
cardiovascular, pulmonary, hepatic, and CNS function may experience serious, life-threatening
or fatal adverse events. Adverse events are frequent, often serious, and sometimes fatal.
Should adverse events, requiring dose modification occur, dosage should be withheld
rather than reduced.
Proleukin has been associated with exacerbation of preexisting
autoimmune disease and inflammatory disorders. In some cases, the onset of new autoimmune
diseases, such as vitiligo, may occur. Symptomatic hyperglycemia and/or diabetes mellitus
have been reported during Proleukin therapy.
All patients should have thorough evaluation and treatment of CNS metastases and have
a negative scan prior to receiving Proleukin therapy. New neurologic signs, symptoms, and anatomic lesions following Proleukin therapy have been reported in patients without evidence of CNS metastases. Neurologic signs and symptoms associated with Proleukin therapy usually improve after discontinuation of Proleukin therapy; however, there are reports of permanent neurologic defects. In patients with known seizure disorders, extreme caution should be exercised as Proleukin may cause seizures.
Patients should have normal cardiac, pulmonary, hepatic, and CNS function at
the start of therapy. Capillary leak syndrome (CLS) begins immediately after Proleukin® (aldesleukin) treatment starts and is marked by increased capillary permeability to protein and fluids and reduced vascular tone.
Proleukin® (aldesleukin) treatment should be withheld for failure to maintain
organ perfusion as demonstrated by altered mental status, reduced urine output, a fall in the systolic blood pressure below 90 mm Hg or onset of cardiac arrhythmias.
Recovery from CLS begins soon after cessation of Proleukin therapy. Usually, within a few hours,
the blood pressure rises, organ perfusion is restored and reabsorption of extravasated fluid
and protein begins.
Kidney and liver function are impaired during Proleukin treatment.
Use of concomitant nephrotoxic or hepatotoxic medications may further increase toxicity to the
kidney or liver.
Mental status changes including irritability, confusion, or depression which occur while
receiving Proleukin may be due to bacteremia or early bacterial sepsis, hypoperfusion, occult CNS malignancy, or direct Proleukin-induced CNS toxicity. Patients should be evaluated for these and other causes of mental status changes. Alterations in mental status due solely to Proleukin therapy may progress for several days before recovery begins. Rarely, patients have sustained permanent neurologic deficits.
Proleukin enhancement of cellular immune function may increase the risk of allograft
rejection in transplant patients.
Serious manifestations of eosinophilia involving eosinophilic infiltration of
cardiac and pulmonary tissues can occur following Proleukin.
The rate of drug-related deaths in the 255 metastatic RCC patients who received
single-agent Proleukin® (aldesleukin) was 4% (11/255); the rate of drug-related deaths in the 270 metastatic melanoma patients who received single-agent Proleukin was 2% (6/270).
In clinical trials, the following life-threatening (Grade 4) adverse events were seen in > 1% of 525
patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: oliguria (6%), anuria (5%), hypotension (3%), respiratory disorder (3%), bilirubinemia (2%), coma (2%), diarrhea (2%), acidosis (1%), acute kidney failure (1%), apnea (1%), cardiovascular disorder (1%), coagulation disorders (1%), confusion (1%), creatinine increase (1%), dyspnea (1%), fever (1%), heart arrest (1%), infection (1%), myocardial infarction (1%), psychosis (1%), sepsis (1%), SGOT increase (1%), stupor (1%), supraventricular tachycardia (1%), thrombocytopenia (1%), ventricular tachycardia (1%), and vomiting (1%). From the same trials, the following adverse events (Grades 1-4) were seen in ≥ 30% of 525 patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: hypotension (71%), diarrhea (67%), oliguria (63%), chills (52%), vomiting (50%), dyspnea (43%), rash (42%), bilirubinemia (40%), thrombocytopenia (37%), nausea (35%), confusion (34%), and creatinine increase (33%).
Please see the full Prescribing Information,
including Boxed Warning, for Proleukin® (aldesleukin) for injection, for intravenous infusion.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
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