aldesleukin (Interleukin 2, Proleukin)
Classes: Biological Response Modifiers; Antineoplastics, Other
Dosing and uses of Interleukin 2, Proleukin (aldesleukin)
Adult dosage forms and strengths
powder for injection
- 22M International Units/vial
Metastatic Renal Cell Carcinoma, Metastatic Melanoma
600,000 International Units/kg (0.037 mg/kg) IV over 15 minutes q8hr x maximum 14 doses, THEn
9 days of rest, then a maximum of 14 more doses
Retreatment: Evaluate after 4 weeks, advisable only if tumor shrinkage & no retreatment contraindications (see package insert for details)
Non-Hodgkin Lymphoma (Orphan)
Designated orphan indication for treatment of non-Hodgkin lymphoma
Orphan indication sponsor
- Prometheus Laboratories, Inc; 9410 Carroll Park Drive; San Diego, CA 92121
Primary Immunodeficiency (Orphan)
Designated orphan indication for treatment of primary immunodeficiency disease associated with T-cell defects
Orphan indication sponsor
- Prometheus Laboratories, Inc; 9410 Carroll Park Drive; San Diego, CA 92121
Monitor
CBC, chemistries, ABGs, pulmonary function
Pediatric dosage forms and strengths
Not recommended
Interleukin 2, Proleukin (aldesleukin) adverse (side) effects
>10%
Hypotension (71%)
Diarrhea (67%)
Oliguria (63%)
Chills (52%)
Vomiting (50%)
Dyspnea (43%)
Rash (42%)
Bilirubinemia (40%)
Thrombocytopenia (37%)
Nausea (35%)
Confusion (34%)
Increased creatinine (33%)
Fever (29%)
Anemia (29%)
Peripheral Edema (28%)
Malaise (27%)
Pruritus (24%)
Asthenia (23%)
Respiratory/lung disorders (11-24%)
Increased hepatic enzymes (10-23%)
Tachycardia (23%)
Somnolence (22%)
Stomatitis (22%)
Anorexia (20%)
Nausea and vomiting (19%)
Exfoliative dermatitis (18%)
Leukopenia (16%)
Weight gain (16%)
Edema (15%)
Infection (13%)
Vasodilation (13%)
Supraventricular tachycardia (12%)
Pain (12%)
Acidosis (12%)
Anxiety (12%)
Dizziness (11%)
Hypocalcemia (11%)
Abdominal pain (11%)
Cough (11%)
1-10%
Arrhythmia (10%)
Rhinitis (10%)
<1%
Immunogenicity: Low titers of anti-aldesleukin antibodies were detected in 66-74% of patients; neutralizing antibodies detected in 1 patient
Postmarketing Reports
Blood and lymphatic system: neutropenia, febrile neutropenia, eosinophilia, lymphocytopenia
Cardiac: Cardiomyopathy, cardiac tamponade Endocrine: hyperthyroidism
Gastrointestinal: Gastritis, intestinal obstruction, colitis
General and administration site conditions: Injection site necrosis
Hepatobiliary: Hepatitis, hepatosplenomegaly, cholecystitis
Immune system: Anaphylaxis, angioedema, urticaria
Infections and infestations: Pneumonia (bacterial, fungal, viral), fatal endocarditis, cellulitis
Musculoskeletal and connective tissue: Myopathy, myositis, rhabdomyolysis
Nervous system: Cerebral lesions, encephalopathy, extrapyramidal syndrome, neuralgia, neuritis, demyelinating neuropathy
Psychiatric: Insomnia
Vascular: Hypertension, fatal subdural and subarachnoid hemorrhage, cerebral hemorrhage, retroperitoneal hemorrhage
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy health care provider in a hospital setting with ICU care
High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS), resulting in hypotension and reduced organ perfusion, which may be severe and can result in death
Use with extreme caution in patients with history of prior cardiac or pulmonary disease
Impaired neutrophil function is associated with treatment. Patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections.
Withhold therapy for patients developing moderate-to-severe lethargy or somnolence. Continued treatment may result in coma.
Contraindications
Hypersensitivity, abnormal thallium stress test or pulmonary function test
Organ allografts
Retreatment for those who experienced complications of drug-induced capillary leak syndrome
- Sustained VTach (=5 beats), Cardiac arrhythmias not controlled or unresponsive to management
- Chest pain with ECG changes, consistent with angina/MI; Cardiac tamponade
- Intubation for >72 hr; renal failure requiring dialysis >72 hr
- Coma or toxic psychosis lasting >48 hours
- Repetitive or difficult to control seizures
- Bowel ischemia/perforation; GI bleeding requiring surgery
Cautions
History of cardiac or pulmonary disease
See Package Insert for retreatment guidelines & contraindications
May exacerbate autoimmune disease
Risk of capillary leak syndrome
Risk of reduced neutrophil chemotaxis, resulting in sepsis/infection risk, use prophylaxis if warranted
Hypotension is dose-limiting
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Interleukin 2, Proleukin (aldesleukin)
Mechanism of action
Recombinant human interleukin-2; stimulates lymphokines-activated killer cells and tumor-infiltrating lymphocytes cells following the interaction between malignant cells and the immune system
Cytolytic for a subset of lymphocytes; promotes differentiation, proliferation and recruitment of B and T cells, thymocytes and natural killer cells
Metabolism
Kidneys
Distribution
Vd: 4-7 L
Elimination
Half-Life: 85 minutes
Clearance: 268 mL/min
Excretion: Urine
Administration
IV Incompatibilities
Additive: Ns
Y-site: dopamine(?), fluorouracil, ganciclovir, KCl(?), lorazepam, pentamidine, prochlorperazine, promethazine
IV Compatibilities
Y-site: amikacin, amphotericin B, Ca-gluconate, diphenhydramine, fluconazole, foscarnet, gentamicin, heparin, MgSO4, metoclopramide, morphine SO4, ondansetron, piperacillin, ranitidine, thiethylperazine, ticarcillin, tobramycin, TMP-SMX, vancomycin
IV Preparation
Concentrations <30 mcg/mL OR concentrations between 30-70 mcg/mL for infusion via ambulatory infusion pump require addition of albumin
Reconstitute/dilute in D5W only; incompatible with sodium chloride solutions or BWI
Gently swirl, do not shake
IV Administration
Infuse over 15 minutes
Do not use in-line filter
Vascular Leak Syndrome Management
If actual body weight increases 10% above baseline, or rales or rhonchi are audible
- Administer furosemide at dosage determined by patient response
- Administer dopamine 2-4 mcg/kg/min to maintain renal blood flow and urine output
- If patient has dyspnea at rest, give supplemental oxygen by face-mask
If patient has severe respiratory distress: intubate patient and provide mechanical ventilation; give ranitidine 50 mg IV q8-12hr as prophylaxis against stress ulcers
Storage
Store lyophilized powder at 2-8°C (36-46°F)
