IntravenousMetastatic melanomaAdult: 600,000 IU/kg 8 hourly given over 15 minutes, for a maximum of 14 doses, repeat after 9 days for a total of 28 doses per course. Retreatment can be done according to patient’s response. Recommendations may vary among countries. Refer to country specific guidelines.
IntravenousMetastatic renal cell carcinomaAdult: Induction cycle: 18x106 IU/m2 daily via continuous infusion for 5 days, followed by 2-6 days of rest. Then additional 5 days of infusion is given, followed by 3 weeks of rest to complete 1 induction cycle. 2nd induction cycle should be given after the 3 weeks of rest. Maintenance cycle: 18x106 IU/m2 via continuous infusion for 5 days for up to 4 maintenance cycles may be given at 4-week intervals. Alternatively, 600,000 IU/kg 8 hourly given over 15 minutes, for a maximum of 14 doses, repeat after 9 days for a total of 28 doses per course. Retreatment can be done according to patient’s response. Recommendations may vary among countries. Refer to country specific guidelines.
SubcutaneousMetastatic renal cell carcinomaAdult: 18x106 IU/m2 once daily for 5 days, followed by 2 days of rest for 1st week. For the following 3 weeks, 18 million IU are given on days 1 and 2 of each week, then 9 million IU on days 3-5 of each week. After 1 week without therapy, the treatment cycle should be repeated. Dose reduction or dosing interruption may be required according to individual safety and tolerability.
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Reconstitute vials with 1.2 mL of sterile water for inj to a concentration of 18 million units/mL (inject towards the side of the vial). Gently swirl. Do not shake. Continuous IV infusion: Further dilute with 5% dextrose in water solution containing 0.1% human albumin. High dose bolus IV infusion: Further dilute with 50 mL of 5% dextrose inj. Recommendations for reconstitution may vary among countries. Refer to specific product guidelines.
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Increased risk of aggregation with 0.9% NaCl or bacteriostatic water for inj.
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Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, presence of all 3 risk factors associated with decreased response rates and median survival (e.g. ECOG performance status of 1 or greater, more than 1 organ with metastatic disease sites, a period of <24 months between the initial diagnosis of a primary tumour and the date the patient is evaluated for aldesleukin therapy), significant history or pre-existing severe cardiac disease; active infection requiring antibiotic treatment; PaO2 <60 mmHg during rest; pre-existing severe major organ dysfunction, CNS metastases or seizure disorders (except for patients with successfully treated brain metastases), abnormal thallium stress test or abnormal pulmonary function tests, pre-existing autoimmune disease; with existing organ allografts; patient with WBC <4,000/mm3, platelets <100,000/mm3, haematocrit <30%, outside the normal range serum bilirubin and creatinine; those who are likely to require corticosteroids. Retreatment is contraindicated in patients who have previously experienced sustained ventricular tachycardia (≥5 beats), uncontrolled/unresponsive cardiac arrhythmias, chest pain with ECG changes (consistent with angina or MI), cardiac tamponade, intubation (>72 hours), renal failure requiring dialysis (>72 hours), coma or toxic psychosis (lasting > 48 hours), refractory seizures, bowel ischaemia or perforation, and gastrointestinal bleeding requiring surgery. Recommendations may vary among countries. Refer to specific product guidelines.
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Patient with diabetes, indwelling central catheter, a normal thallium stress test and a normal pulmonary function test with a history of cardiac or pulmonary disease; restrict therapy for those with normal cardiopulmonary functions as defined by thallium stress test and formal pulmonary function testing. Fluid restricted patient or those who may poorly tolerate oedema; those with fixed requirements for large volumes of fluid (e.g. hypercalcaemic states). Transplant recipients. Elderly. Pregnancy and lactation.
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Significant: Moderate to severe lethargy or somnolence (may lead to coma with continuous use); impaired neutrophil function (e.g. reduced chemotaxis), increased risk of disseminated infection (e.g. sepsis, bacterial endocarditis, septic thrombophlebitis, peritonitis, pneumonia), mental status changes (e.g. irritability, confusion, or depression), hypothyroidism (may be preceded by hyperthyroidism), hyperglycaemia, onset of diabetes mellitus, myocardial injury (e.g. findings compatible with MI or myocarditis), eosinophilia (e.g. eosinophilic infiltration of cardiac and pulmonary tissues), impaired hepatic and renal function, increased hepatic transaminases, serum bilirubin, urea, and creatinine; exacerbated effusions from serosal surfaces (e.g. pericardial effusions), activation of quiescent Crohn’s disease, impaired kidney and liver function, increased risk of allograft rejection. Rarely, permanent neurologic deficits.
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, leucopenia, coagulopathy (e.g. disseminated intravascular coagulation).
Eye disorders: Conjunctivitis.
Gastrointestinal disorders: Nausea with or without vomiting, diarrhoea, stomatitis, taste loss, dyspepsia, constipation, dysphagia, gastrointestinal bleeding, rectal haemorrhage, haematemesis, ascites, cheilitis, gastritis.
General disorders and administration site conditions: Inj site reaction, pain, inflammation; fever (with or without chills), malaise, asthenia, fatigue, pain, oedema, mucositis, inj site nodule, hypothermia.
Hepatobiliary disorders: Hyperbilirubinaemia, hepatomegaly, hepatosplenomegaly.
Investigations: Increased alkaline phosphatase, lactic dehydrogenase, weight gain or loss.
Metabolism and nutrition disorders: Anorexia, dehydration, acidosis, hypo- hyper-calcaemia, hyperkalaemia.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia.
Nervous system disorders: Headache, dizziness, paraesthesia, syncope, neuropathy, speech disorders.
Psychiatric disorders: Anxiety, insomnia, irritability, agitation, depression, hallucinations.
Renal and urinary disorders: Oliguria.
Respiratory, thoracic and mediastinal disorders: Respiratory tract infections, cough, dyspnoea, pulmonary oedema, pleural effusions, hypoxia, haemoptysis, epistaxis, nasal congestion, rhinitis.
Skin and subcutaneous tissue disorders: Rash, erythema, exfoliative dermatitis, pruritus, sweating, alopecia, urticaria.
Vascular disorders: Phlebitis, hypertension.
Potentially Fatal: Capillary leak syndrome leading to hypotension and reduced organ perfusion (increased risk with IV administration), exacerbated autoimmune disease.
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Perform thallium tress test before treatment initiation. Monitor daily during treatment: CBC with differential and platelets, electrolytes, blood chemistries (e.g. blood glucose), renal function, LFTs, chest x-ray, pulmonary function tests and arterial blood gases, thyroid function tests (TSH at baseline and every 2-3 months during treatment), cardiac function, vital signs (daily; hourly if hypotensive), weight and fluid intake and output. Perform cardiac monitoring for rhythm (if the patient is hypotensive), ECG monitoring (if an abnormal complex rhythm is found). Assess signs of infection and CNS toxicity.
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Decreased antitumour effectiveness with glucocorticoids. May cause acute, atypical adverse effects with iodinated contrast media. Exacerbated autoimmune disorders (e.g. crescentic IgA glomerulonephritis, oculo-bulbar myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid, and Stevens-Johnson syndrome) and increased risk of severe rhabdomyolysis and myocardial injury, including MI, myocarditis, and ventricular hypokinesia with interferon-α. Enhanced hypotensive effect with β-blockers and other antihypertensive agents. Increased risk of nephrotoxicity with aminoglycosides, indomethacin; hepatotoxicity with methotrexate, asparaginase; cardiotoxicity with doxorubicin; myelotoxicity with cytotoxic chemotherapeutic agents.
Potentially Fatal: Increased risk of tumour lysis syndrome with cisplatin, vinblastine, and dacarbazine.
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Description:
Mechanism of Action: Aldesleukin is a human recombinant interleukin-2 (IL-2) product. The exact mechanism of action is still unknown, but it is shown to promote the proliferation of T-lymphocytes which amplifies immune response to antigen. It also stimulates the lymphokine-activated killer (LAK) cells and tumour-infiltrating lymphocytes (TIL) cells.
Pharmacokinetics:
Absorption: Bioavailability: 31-47% (SC).
Distribution: Distributed particularly into the plasma, lymphocytes, lungs, liver, kidney, and spleen. Volume of distribution: 6.3-7.9 L.
Metabolism: Metabolised in the cells lining the proximal convoluted tubules of the kidney into amino acids.
Excretion: Via urine (as metabolites). Elimination half-life: 85 minutes (IV); 5.3 hours (SC).
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Store intact vials between 2-8°C. Protect from light. Do not freeze. Store reconstituted/diluted solutions between 2-30°C; stable for up to 48 hours. Do not freeze.
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L03AC01 - aldesleukin ; Belongs to the class of interleukins. Used as immunostimulants.
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Anon. Aldesleukin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/04/2022. Buckingham R (ed). Interleukin-2. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/04/2022. Joint Formulary Committee. Aldesleukin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/04/2022. Novartis New Zealand Limited. Proleukin 18 million International Units, Powder for Solution for Injection or Infusion data sheet 4 July 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 01/04/2022. Proleukin 18x106 IU Powder for Solution for Injection or Infusion (Novartis Pharmaceuticals UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/04/2022. Proleukin Injection, Powder, Lyophilized, for Solution (Clinigen Group PLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/04/2022.
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