proleukin

Important safety information

Renal Toxicity: Monitor renal function at baseline and throughout treatment. Withhold Proleukin or permanently discontinue, based on severity. ( 2.4 , 5.4 ) Immune-mediated Adverse Reactions: Exacerbation of pre-existing autoimmune disease or initial presentation of autoimmune and inflammatory disorders can occur in any system or tissue. Proleukin may increase the risk of allograft rejection in transplant patients. Monitor patients and treat as indicated. ( 5.5 ) Severe Hypersensitivity Reaction: Permanently discontinue Proleukin for severe hypersensitivity reactions. ( 4 , 5.9 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Capillary Leak Syndrome Severe and life-threatening capillary leak syndrome (CLS) characterized by hypotension, dyspnea, edema, and hypoalbuminemia can occur with Proleukin, and can result in end organ toxicity including cardiac, respiratory, renal, hepatic toxicity, or death. Do not administer Proleukin to patients with significant cardiac, pulmonary, renal, or hepatic impairment. Avoid concomitant use of Proleukin with other products known to cause hypotension including antihypertensive drugs, those that cause renal toxicity, or hepatotoxicity. CLS may begin immediately after Proleukin treatment is initiated. Monitor for signs and symptoms of CLS including assessments of vital signs, weight, fluid intake, albumin levels and urine output. Withhold or discontinue Proleukin for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, oxygen saturation <90%, a fall in the systolic blood pressure below 90 mm Hg, or onset of cardiac arrhythmias. Initiate standard management for CLS, which may include intensive care [see Dosage and Administration (2.4) , Use in Specific Populations (8.1) ] . 5.2 Neurologic Toxicity Proleukin can cause neurologic toxicities including mental status changes, speech difficulties, cortical blindness, limb or gait ataxia, hallucinations, agitation, obtundation, demyelinating polyneuropathy, and coma. Alterations in mental status may progress for several days before recovery begins. Permanent neurologic deficits have occurred. Radiological findings included multiple and, less commonly, single cortical lesions on MRI and evidence of demyelination. One case of possible cerebral vasculitis has been reported. Monitor patients for signs and symptoms of neurological toxicity during Proleukin treatment. Withhold Proleukin in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma. Permanently discontinue Proleukin for coma or toxic psychosis lasting >48 hours or for repetitive or difficult to control seizures [see Dosage and Administration (2.4) ]. Evaluate and treat CNS metastases prior to initiation of Proleukin. If possible, avoid concomitant use of Proleukin with other product(s) with a known potential to cause neurotoxicity, and avoid Proleukin in patients with seizure disorders or abnormal intracranial imaging [see Contraindications (4) , Adverse Reactions (6.1 , 6.2) ] . Concomitant use of Proleukin with other products that cause neurotoxicity may result in a greater risk of severe neurotoxicity. 5.3 Serious Infections Including Sepsis Proleukin can cause impaired neutrophil function (reduced chemotaxis) and an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Treat pre-existing bacterial infections prior to initiating Proleukin. Consider antibiotic prophylaxis in patients with indwelling central lines. Monitor patients for the development of signs and symptoms of infection during treatment and withhold Proleukin based on severity [see Dosage and Administration (2.4) ]. 5.4 Renal Toxicity Serious renal toxicity, including oliguria and renal failure can occur with Proleukin [see Adverse Reactions (6.1 , 6.2) ] . Pre-existing renal impairment or coadministration of Proleukin with other products known to cause renal toxicity may increase this risk. If possible, avoid concomitant use of Proleukin with other product(s) with a known potential to cause renal toxicity. Serum creatinine should be ≤1.5 mg/dL before beginning Proleukin. Monitor serum creatinine at baseline and daily throughout each course of therapy. Withhold Proleukin, or permanently discontinue, based on severity [see Dosage and Administration (2.4) ] . 5.5 Immune-mediated Adverse Reactions Exacerbation of pre-existing autoimmune disease or initial presentation of autoimmune and inflammatory disorders has been reported following treatment with Proleukin. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. These have included exacerbation of Crohn's disease, colitis, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, bullous pemphigoid, myocarditis, myositis, and neuritis including optic neuritis resulting in blindness [see Adverse Reactions (6.2) ] . Proleukin may increase the risk of allograft rejection in transplant patients [see Contraindications (4) ] . Hypothyroidism, sometimes preceded by hyperthyroidism, has been reported following Proleukin treatment. Evaluate thyroid function at baseline and periodically during treatment and initiate thyroid replacement therapy as clinically indicated. Hyperglycemia and/or diabetes mellitus has been reported during Proleukin therapy. Monitor patients for hyperglycemia and initiate treatment with insulin as clinically indicated. 5.6 Embryo-Fetal Toxicity Based on findings in an animal study and its mechanism of action, Proleukin may cause fetal harm or loss of pregnancy when administered to a pregnant woman. In pregnant rats, aldesleukin has been shown to have embryolethal effects at doses 27 times and maternal toxicities at doses 2.1 times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with Proleukin [see Use in Specific Populations (8.1 , 8.3) ]. 5.7 Serious Manifestations of Eosinophilia Serious manifestations of eosinophilia involving eosinophilic infiltration of cardiac and pulmonary tissues can occur following Proleukin. 5.8 Delayed Adverse Reactions to Iodinated Contrast Media A review of the literature revealed that 12.6% (range 11-28%) of 501 patients treated with various interleukin-2-containing regimens who were subsequently administered radiographic iodinated contrast media experienced acute, atypical adverse reactions. The onset of symptoms usually occurred within hours (most commonly 1 to 4 hours) following the administration of contrast media. These reactions include fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. These reactions may resemble the immediate side effects caused by interleukin-2 administration. Most events were reported to occur when contrast media was given within 4 weeks after the last dose of interleukin-2. These events were also reported to occur when contrast media was given several months after interleukin-2 treatment [see Adverse Reactions (6.2) ] . 5.9 Severe Hypersensitivity Reactions Proleukin can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue Proleukin in patients who experience a severe hypersensitivity reaction [see Contraindications (4) , Adverse Reactions (6.2) ]. 5.10 Infusion-Related Reactions Proleukin can cause fevers, chills, or rigors. Premedicate patients with an antipyretic prior to beginning Proleukin and continue during treatment as needed for fever [see Adverse Reactions (6.2) and Dosage and Administration (2.3) ].