aldesleukin (Interleukin 2, Proleukin)

Dosing and uses of Interleukin 2, Proleukin (aldesleukin)

• Adult
• Pediatric

 

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)