Aldesleukin

Proleukin is a lymphocyte growth factor indicated for: The treatment of adults with metastatic renal cell carcinoma. The treatment of adults with metastatic melanoma.

Aldesleukin is an interleukin-2 lymphocyte growth factor. The antitumor activity of aldesleukin has not been fully characterized. In vitro studies performed on human cell lines show enhancement of lymphocyte mitogenesis and cytotoxicity, induction of killer cell activity [lymphokine-activated killer (LAK) and natural killer (NK) cells] and interferon gamma production, and proliferation of human interleukin-2-dependent cell lines. Administration of aldesleukin in animals and humans produces multiple immunological effects in a dose-dependent manner. These effects include activation of cellular immunity and the production of cytokines including tumor necrosis factor, IL-1, and interferon gamma. In vivo experiments in murine melanoma and sarcoma tumor models have shown inhibition of tumor growth.

Administer Proleukin in an inpatient hospital setting with an intensive care facility. Evaluate cardiovascular, pulmonary, neurologic and renal function before beginning Proleukin. See Full Prescribing Information for Premedication and Supportive medications. Recommended dosage: 600,000 IU/kg (0.037 mg/kg) every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Following 9 days of rest, repeat the schedule for a maximum of another 14 doses (total of 28 doses per course, as tolerated). Evaluate patients approximately 4 weeks after completion of a course of therapy and again immediately prior to the start of the next course. Dose modification for toxicity should be accomplished by withholding or interrupting a dose. Follow reconstitution and dilution procedures.

Severe Hypersensitivity Reactions Proleukin is contraindicated in patients with a known history of severe hypersensitivity to aldesleukin or any component of the Proleukin formulation. Organ Allografts Proleukin is contraindicated in patients with organ allografts. Significant Organ Impairment Proleukin is contraindicated in patients with significant cardiac (including those with an abnormal cardiac ejection fraction, impaired wall motion, or significant coronary artery disease), pulmonary (including those with an FEV1 ≤ 2 liters or < 75% predicted for height and age), renal, hepatic, or CNS impairment. Hypersensitivity to aldesleukin. Organ allografts. Significant organ impairment.

Boxed warning (capillary leak syndrome (cls), neurologic toxicities and serious infections): Capillary leak syndrome (CLS), including life threatening or fatal reactions, has occurred in patients treated with Proleukin. Do not administer Proleukin to patients with significant cardiac, pulmonary, renal, and hepatic impairment. Administer Proleukin in a hospital setting with an intensive care facility. Renal Toxicity: Monitor renal function at baseline and throughout treatment. Withhold Proleukin or permanently discontinue, based on severity. 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.

The following clinically significant adverse reactions are described elsewhere in the labeling: Capillary Leak Syndrome. Neurotoxicity. Serious Infections Including Sepsis. Renal Toxicity. Immune-Mediated Adverse Reactions. Serious Manifestations of Eosinophilia. Severe Hypersensitivity Reactions. Infusion-Related Reactions. Most common (≥ 30%) adverse reactions including laboratory abnormalities are hypotension, hyperbilirubinemia, dyspnea, rash, diarrhea, oliguria, chills, vomiting, thrombocytopenia, nausea, confusional state and increased creatinine.

Drug interaction studies with Proleukin have not been conducted. The drug interaction information described below have been observed post-marketing. See Full Prescribing Information for important drug interactions.

Store unopened vials refrigerated at 2° to 8°C (36° to 46°F) in the original carton to protect from light.