Aldesleukin

Capillary Leak Syndrome (Cls), Neurologic Toxicities And Serious Infections

Capillary Leak Syndrome

  • Severe and life-threatening capillary leak syndrome (CLS) characterized by hypotension, dyspnea, edema, and hypoalbuminemia can occur with aldesleukin, and can result in end organ toxicity including cardiac, respiratory, renal, hepatic toxicity, or death. Do not administer aldesleukin to patients with significant cardiac, pulmonary, renal, or hepatic impairment. Avoid concomitant use of aldesleukin with other products known to cause hypotension including antihypertensive drugs, those that cause renal toxicity, or hepatotoxicity.
  • CLS may begin immediately after aldesleukin 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 aldesleukin 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)].

Neurologic Toxicity

  • Aldesleukin 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 aldesleukin treatment. Withhold aldesleukin in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma. Permanently discontinue aldesleukin 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 aldesleukin. If possible, avoid concomitant use of aldesleukin with other product(s) with a known potential to cause neurotoxicity, and avoid aldesleukin in patients with seizure disorders or abnormal intracranial imaging [see Contraindications (4), Adverse Reactions (6.1, 6.2)]. Concomitant use of aldesleukin with other products that cause neurotoxicity may result in a greater risk of severe neurotoxicity.

Serious Infections Including Sepsis

  • Aldesleukin 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 aldesleukin. Consider antibiotic prophylaxis in patients with indwelling central lines. Monitor patients for the development of signs and symptoms of infection during treatment and withhold aldesleukin based on severity [see Dosage and Administration (2.4)].

Monitoring data

  • Pre-existing bacterial infections should be treated prior to initiation of therapy. Antibiotic prophylaxis has been used in patients with indwelling central lines to reduce incidence of staphylcoccal infections. This group is at increased risk for infection with gram positive organisms.
  • Baseline normal cardiac and pulmonary function defined by thallium stress testing and formal pulmonary function testing. Use extreme caution in patients with normal test results who have history of cardiac or pulmonary disease.
  • CLS characterized by loss of vascular tone & extravasation of plasma proteins and fluid into extravascular space. May result in hypotension, reduced organ perfusion, arrhtyhmias, angina, MI, respiratory insufficiency, GI bleeding/infarction, renal insufficiency, edema, and/or mental status changes.
  • Baseline testing prior to therapy initiation and daily during drug administration: standard hematological tests (e.g., CBC, differential & platelet counts), blood chemistry (electrolytes, renal/hepatic function), & chest x-rays.
  • Baseline serum creatinine should be < 1>
  • Daily monitoring should include vital signs, weight, fluid intake/output, & cardiac function. Repeat pulmonary monitoring regularly during therapy.
  • If evidence of cardiac ischemia or CHF, hold therapy & repeat thallium testing.

Patient counseling

Package inserts

Aldesleukin

Additional information

Updated: July 2024