Aldesleukin Disease Interactions

Aldesleukin may exacerbate existing or activate quiescent autoimmune disease. Therapy with aldesleukin should be administered cautiously in patients with autoimmune diseases.

The use of aldesleukin is contraindicated in patients with abnormal cardiac function as indicated by a thallium stress test. Therapy with aldesleukin should be administered with extreme caution in patients with a normal thallium stress test who have a history of cardiac disease. Close clinical monitoring of cardiac function is required. When adverse events occur that require dosage modification, dosages should be withheld rather than reduced . Subsequent treatment with aldesleukin is contraindicated in patients with sustained ventricular tachycardia, rhythm disturbances uncontrolled or unresponsive to management, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, or pericardial tamponade.

Aldesleukin can cause Capillary Leak Syndrome resulting in ascites or pulmonary edema. Administration of IV fluids may be necessary to maintain organ perfusion and blood pressure. Aldesleukin should be administered cautiously in patients with fixed fluid requirements and/or those adversely affected by fluid overload.

Hepatotoxicity such as elevated bilirubin, transaminase and alkaline phosphatase levels have been reported in over 55% of patients administered aldesleukin. Hepatotoxicity is generally reversible, however, hepatic failure resulting in death has been reported. Therapy with aldesleukin should be administered cautiously in patients with compromised hepatic function. When adverse events occur that require dosage modification, dosages should be withheld rather than reduced. Clinical monitoring of hepatic function is recommended.

Hypotension, primarily associated with capillary leak syndrome, has been reported in 85% of patients administered aldesleukin. Seventy-one percent of patients with hypotension required pressor management. Therapy with aldesleukin should be administered cautiously in patients predisposed to hypotension.

Aldesleukin induces myelosuppression, primarily thrombocytopenia and anemia. Leukopenia has been reported. Therapy with aldesleukin should be administered cautiously in patients with compromised bone marrow reserve. Clinical monitoring of hematopoietic function is recommended. Subsequent treatment with aldesleukin is contraindicated in patients requiring surgery for GI bleeding or in those patients with bowel ischemia/perforation.

The use of aldesleukin may be contraindicated in patients with infections, particularly bacterial diseases. Aldesleukin can interfere with neutrophil chemotaxis and increase the risk of disseminated infections, including bacterial endocarditis and sepsis. Therefore, preexisting bacterial infections should be adequately treated prior to initiation of aldesleukin therapy. Close clinical monitoring of hematopoietic function is recommended during therapy. Since there is increasing evidence that neutrophils may also play important roles in viral and other infections, it may be reasonable in some cases to defer aldesleukin treatment in patients with active nonbacterial infections.

The use of aldesleukin is contraindicated in patients with allograft organ transplants. Aldesleukin possesses immunoregulatory properties that may increase the risk of organ rejection, including enhancement of lymphocyte mitogenesis and cytotoxicity and induction of killer cell activity.

The use of aldesleukin should be restricted to patients with adequate ventilatory function (baseline FEV1 > 2 L or >= 75% of the predicted value based on height and age). Extreme caution should be used in treating patients with normal test results but have a history of pulmonary disease. Pulmonary congestion and dyspnea have been reported in over 50% of patients receiving the recommended dosage of aldesleukin. Respiratory adverse effects are often associated with the capillary leak syndrome induced by aldesleukin and may also include pulmonary edema, respiratory failure requiring intubation, tachypnea, pleural effusion, wheezing, apnea, pneumothorax, hemoptysis, respiratory arrest, and pulmonary emboli. During therapy, pulmonary function should be monitored regularly by clinical examination, assessment of vital signs and pulse oximetry, and arterial blood gas determinations as needed. When toxicities occur that require a dosage modification, doses should be withheld rather than reduced. Subsequent treatment with aldesleukin is contraindicated in patients who develop respiratory failure requiring intubation for longer than 72 hours.

Renal toxicity such as oliguria/anuria and elevated BUN and serum creatinine has been reported in > 60% of patients during aldesleukin therapy. Renal toxicity is generally reversible, however, patients with renal impairment are at increased risk for more severe and prolonged renal dysfunction. Therapy with aldesleukin should be administered cautiously in patients with compromised renal function. Clinical monitoring of renal function is recommended. When adverse events occur that require dosage modification, dosages should be withheld rather than reduced. Subsequent treatment with aldesleukin is contraindicated in patients experiencing renal dysfunction that requires greater than seventy-two hours of dialysis.

Aldesleukin can induce seizures. Therapy with aldesleukin should be administered with extreme caution in patients with or predisposition to seizure disorders. When adverse events occur that require dosage modification, dosages should be withheld rather than reduced . Subsequent treatment with aldesleukin is contraindicated in patients with repetitive or difficult to control seizures.

Mental status changes such as lethargy, somnolence, depression, confusion or agitation were reported in over 70% of patients administered aldesleukin. Therapy with aldesleukin should be administered cautiously to patients with or predisposition to altered mental status. When adverse events occur that require dosage modification, dosages should be withheld rather than reduced. Clinical monitoring of mental status is recommended.