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Aldesleukin

Medically reviewed by Drugs.com. Last updated on Aug 15, 2020.

Pronunciation

(al des LOO kin)

Index Terms

  • IL-2
  • Interleukin 2
  • Interleukin-2
  • Lymphocyte Mitogenic Factor
  • Recombinant Human Interleukin-2
  • T-Cell Growth Factor
  • TCGF
  • Thymocyte Stimulating Factor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Proleukin: 22,000,000 units (1 ea)

Brand Names: U.S.

  • Proleukin

Pharmacologic Category

  • Antineoplastic Agent, Biological Response Modulator
  • Antineoplastic Agent, Miscellaneous

Pharmacology

Aldesleukin is a human recombinant interleukin-2 product which promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.

Distribution

Primarily into plasma, lymphocytes, lungs, liver, kidney, and spleen; Vd: 6.3 to 7.9 L (Whittington 1993)

Metabolism

Renal (metabolized to amino acids in the cells lining the proximal convoluted tubules of the kidney)

Excretion

Urine (primarily as metabolites)

Clearance: 268 mL/minute

Half-Life Elimination

IV:

Children: Distribution: 14 ± 6 minutes; Elimination: 51 ± 11 minutes

Adults: Distribution: 13 minutes; Terminal: 85 minutes

Use: Labeled Indications

Melanoma, metastatic: Treatment of metastatic melanoma in adults.

Renal cell cancer, metastatic: Treatment of metastatic renal cell cancer in adults.

Limitations of use: Careful patient selection is necessary. Assess performance status (PS); patients with a more favorable PS (Eastern Cooperative Oncology Group [ECOG] PS 0) at treatment initiation respond better to aldesleukin (higher response rate and lower toxicity). Experience in patients with ECOG PS >1 is limited.

Contraindications

Known history of hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or abnormal pulmonary function tests; patients with organ allografts. Re-treatment is contraindicated in patients who have experienced sustained ventricular tachycardia (≥5 beats), uncontrolled or unresponsive cardiac arrhythmias, chest pain with ECG changes consistent with angina or myocardial infarction, cardiac tamponade, intubation >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or refractory seizures, bowel ischemia/perforation, or GI bleeding requiring surgery.

Dosing: Adult

Consider premedication with an antipyretic to reduce fever, an H2 antagonist for prophylaxis of GI irritation/bleeding, antiemetics, and antidiarrheals; continue premedications for 12 hours after the last aldesleukin dose. Antibiotic prophylaxis is recommended to reduce the incidence of infection. Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.

Melanoma, metastatic: IV: 600,000 units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course (Atkins 1999); re-treat if tumor shrinkage observed (and if no contraindications) at least 7 weeks after hospital discharge date.

Off-label dosing: 720,000 units/kg every 8 hours for 14 doses; repeat cycle after a 6- to 9-day rest period. Additional courses of treatment were administered if tumor regression occurred or for stable disease (up to maximum of 5 treatment courses); each course of therapy was typically separated by a 6- to 12-week interval (Atkins 1999) or 720,000 units/kg every 8 hours for 12 to 15 doses; repeat with a second cycle ~14 days after the first dose of the initial cycle (Smith 2008).

Renal cell carcinoma, metastatic: IV: 600,000 units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course (McDermott 2005); re-treat if tumor shrinkage observed (and if no contraindications) at least 7 weeks after hospital discharge date.

Off-label dosing: 720,000 units/kg every 8 hours for up to 12 doses; repeat with a second cycle 10 to 15 days later (Klapper 2008).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing and frequency may vary by indication, protocol, and/or treatment phase and hematologic response; refer to specific protocols. Consider premedication with an antipyretic to reduce fever, an H2 antagonist for prophylaxis of gastrointestinal irritation/bleeding, antiemetics, and antidiarrheals; continue for 12 hours after the last aldesleukin dose. Antibiotic prophylaxis is recommended to reduce the incidence of infection. Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011):

Neuroblastoma: Limited data available: Children and Adolescents: IV: 3 million units/m2/day continuous infusion over 24 hours for 4 consecutive days during week 1 and 4.5 million units/m2/day continuous infusion over 24 hours for 4 consecutive days during week 2 of cycles 2 and 4 (regimen also includes isotretinoin, dinutuximab [an anti-GD2 antibody], and sargramostim) (Yu 2010)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: There are no pediatric-specific recommendations; the presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.

Adult:

Withhold or interrupt a dose for toxicity; do not reduce the dose.

Cardiovascular toxicity:

Atrial fibrillation, supraventricular tachycardia, or bradycardia that is persistent, recurrent, or requires treatment: Withhold dose; may resume when asymptomatic with full recovery to normal sinus rhythm.

Systolic BP <90 mm Hg (with increasing pressor requirements): Withhold dose; may resume treatment when systolic BP ≥90 mm Hg and stable or pressor requirements improve.

Any ECG change consistent with MI, ischemia or myocarditis (with or without chest pain), or suspected cardiac ischemia: Withhold dose; may resume when asymptomatic, MI/myocarditis have been ruled out, suspicion of angina is low, or there is no evidence of ventricular hypokinesia.

CNS toxicity: Mental status change, including moderate confusion or agitation. Withhold dose; may resume when resolved completely.

Dermatologic toxicity: Bullous dermatitis or marked worsening of preexisting skin condition: Withhold dose; may treat with antihistamines or topical products (do not use topical steroids); may resume with resolution of all signs of bullous dermatitis.

Gastrointestinal: Stool guaiac repeatedly >3 to 4+: Withhold dose; may resume with negative stool guaiac.

Infection: Sepsis syndrome, clinically unstable: Withhold dose; may resume when sepsis syndrome has resolved, patient is clinically stable, and infection is under treatment.

Respiratory toxicity: Oxygen saturation <90%: Withhold dose; may resume when >90%.

Retreatment with aldesleukin is contraindicated with the following toxicities: Sustained ventricular tachycardia (≥5 beats), uncontrolled or unresponsive cardiac arrhythmias, chest pain with ECG changes consistent with angina or MI, cardiac tamponade, intubation >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or refractory seizures, bowel ischemia/perforation, or GI bleeding requiring surgery

Dosing: Adjustment for Toxicity

Withhold or interrupt a dose for toxicity; do not reduce the dose.

Cardiovascular toxicity:

Atrial fibrillation, supraventricular tachycardia, or bradycardia that is persistent, recurrent, or requires treatment: Withhold dose; may resume when asymptomatic with full recovery to normal sinus rhythm.

Systolic BP <90 mm Hg (with increasing pressor requirements): Withhold dose; may resume treatment when systolic BP ≥90 mm Hg and stable or pressor requirements improve.

Any ECG change consistent with MI, ischemia or myocarditis (with or without chest pain), or suspected cardiac ischemia: Withhold dose; may resume when asymptomatic, MI/myocarditis have been ruled out, suspicion of angina is low, or there is no evidence of ventricular hypokinesia.

CNS toxicity: Mental status change, including moderate confusion or agitation: Withhold dose; may resume when resolved completely.

Dermatologic toxicity: Bullous dermatitis or marked worsening of preexisting skin condition: Withhold dose; may treat with antihistamines or topical products (do not use topical steroids); may resume with resolution of all signs of bullous dermatitis.

Gastrointestinal: Stool guaiac repeatedly >3-4+: Withhold dose; may resume with negative stool guaiac.

Infection: Sepsis syndrome, clinically unstable: Withhold dose; may resume when sepsis syndrome has resolved, patient is clinically stable, and infection is under treatment.

Respiratory toxicity: Oxygen saturation <90%: Withhold dose; may resume when ≥90%.

Re-treatment with aldesleukin is contraindicated with the following toxicities: Sustained ventricular tachycardia (≥5 beats), uncontrolled or unresponsive cardiac arrhythmias, chest pain with ECG changes consistent with angina or MI, cardiac tamponade, intubation >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or refractory seizures, bowel ischemia/perforation, or GI bleeding requiring surgery.

Reconstitution

Reconstitute vials with 1.2 mL SWFI (preservative free) to a concentration of 18 million units (1.1 mg)/1 mL (sterile water should be injected towards the side of the vial). Gently swirl; do not shake. Further dilute with 50 mL of D5W. Smaller volumes of D5W should be used for doses ≤1.5 mg; avoid concentrations <30 mcg/mL and >70 mcg/mL (an increased variability in drug delivery has been seen). Plastic (polyvinyl chloride) bags result in more consistent drug delivery and are recommended. Filtration may result in loss of bioactivity.

Avoid bacteriostatic water for injection and NS for reconstitution or dilution; increased aggregation may occur.

Administration

IV: Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.

Administer as IV infusion over 15 minutes (do not administer with an inline filter). Allow solution to reach room temperature prior to administration. Flush before and after with D5W, particularly if maintenance IV line contains sodium chloride.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. Plastic (polyvinyl chloride) bags result in more consistent drug delivery and are recommended. According to the manufacturer, reconstituted vials and solutions diluted in D5W for infusion are stable for 48 hours at room temperature or refrigerated, although refrigeration is preferred because reconstituted and diluted solutions do not contain preservatives. Do not freeze.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Corticosteroids: May diminish the antineoplastic effect of Aldesleukin. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide (Nasal); Desonide; DexAMETHasone (Ophthalmic); Difluprednate; Flunisolide (Nasal); Fluocinolone (Ophthalmic); Fluticasone (Nasal); Hydrocortisone (Ophthalmic); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic). Avoid combination

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Management: Consider using lower doses to minimize toxicity of this combination. Only coadminister aldesleukin and interferons (alfa) in patients in whom potential benefits outweigh the risk of severe toxicity. Monitor renal and cardiac function closely if combined. Consider therapy modification

Iodinated Contrast Agents: Aldesleukin may enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Hypotension (71%, grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), supraventricular tachycardia (12%, grade 4: 1%), cardiac disease (11%; includes blood pressure changes, HF and ECG changes)

Central nervous system: Chills (52%), confusion (34%, grade 4: 1%), malaise (27%), drowsiness (22%), anxiety (12%), pain (12%), dizziness (11%)

Dermatologic: Skin rash (42%), pruritus (24%), exfoliative dermatitis (18%)

Endocrine & metabolic: Weight gain (16%), acidosis (12%, grade 4: 1%), hypomagnesemia (12%), hypocalcemia (11%)

Gastrointestinal: Diarrhea (67%, grade 4: 2%), vomiting (19% to 50%, grade 4: 1%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), abdominal pain (11%)

Genitourinary: Oliguria (63%, grade 4: 6%)

Hematologic & oncologic: Thrombocytopenia (37%, grade 4: 1%), anemia (29%), leukopenia (16%)

Hepatic: Hyperbilirubinemia (40%, grade 4: 2%), increased serum AST (23%, grade 4: 1%)

Immunologic: Antibody development (66% to 74%)

Infection: Infection (13%, grade 4: 1%)

Neuromuscular & skeletal: Weakness (23%)

Renal: Increased serum creatinine (33%, grade 4: 1%)

Respiratory: Dyspnea (43%, grade 4: 1%), pulmonary disease (24%; includes pulmonary congestion, rales, rhonchi), cough (11%), respiratory tract disease (11%; includes acute respiratory distress syndrome, pulmonary infiltrates, and pulmonary changes)

Miscellaneous: Fever (29%, grade 4: 1%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (10%), cardiac arrest (grade 4: 1%), myocardial infarction (grade 4: 1%), ventricular tachycardia (grade 4: 1%)

Central nervous system: Coma (grade 4: 2%), psychosis (grade 4: 1%), stupor (grade 4: 1%)

Gastrointestinal: Enlargement of abdomen (10%)

Genitourinary: Anuria (grade 4: 5%)

Hematologic & oncologic: Blood coagulation disorder (grade 4: 1%; includes intravascular coagulopathy)

Hepatic: Increased serum alkaline phosphatase (10%)

Infection: Sepsis (grade 4: 1%)

Renal: Acute renal failure (grade 4: 1%)

Respiratory: Rhinitis (10%), apnea (grade 4: 1%)

<1%, postmarketing, and/or case reports: Agitation, allergic interstitial nephritis, anaphylaxis, angioedema, asthma, atrial arrhythmia, atrioventricular block, blindness (transient or permanent), bowel infarction, bradycardia, brain disease, bullous pemphigoid, capillary leak syndrome, cardiomyopathy, cellulitis, cerebral edema, cerebral lesion, cerebral vasculitis, cerebrovascular accident, cholecystitis, colitis, delirium, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, endocarditis, eosinophilia, exacerbation of Crohn's disease, extrapyramidal reaction, gastritis, hematemesis, hemoptysis, hemorrhage (including cerebral, gastrointestinal, retroperitoneal, subarachnoid, subdural), hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperthyroidism, hyperuricemia, hyperventilation, hypothermia, hypoventilation, hypoxia, IgA glomerulonephritis (crescentic), increased blood urea nitrogen, increased nonprotein nitrogen, inflammatory arthritis, insomnia, intestinal necrosis, intestinal obstruction, intestinal perforation, ischemic heart disease, leukocytosis, lymphocytopenia, malignant hyperthermia, meningitis, myasthenia gravis (oculo-bulbar), mydriasis, myocarditis, myopathy, myositis, neuralgia, neuritis, neuropathy, neutropenia, optic neuritis, pancreatitis, paranoia, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolism, renal tubular necrosis, respiratory acidosis, respiratory arrest, respiratory failure, restricted systemic blood flow, rhabdomyolysis, scleroderma, seizure, shock, Stevens-Johnson syndrome, syncope, thrombosis, thyroiditis, tissue necrosis at injection site, tracheoesophageal fistula, transient ischemic attacks, urticaria, ventricular premature contractions

ALERT: U.S. Boxed Warning

Cardiopulmonary disease:

Restrict therapy with aldesleukin to patients with normal cardiac and pulmonary functions as defined by thallium stress testing and formal pulmonary function testing. Use extreme caution in patients with a normal thallium stress test and a normal pulmonary function test who have a history of cardiac or pulmonary disease.

Experienced physician:

Administer aldesleukin in a hospital setting under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available.

CNS toxicity:

Withhold aldesleukin administration in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma.

Capillary leak syndrome:

Aldesleukin administration has been associated with capillary leak syndrome (CLS) which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. CLS results in hypotension and reduced organ perfusion which may be severe and can result in death. CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes.

Infections:

Aldesleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and with an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting bacterial infections should be adequately treated prior to initiation of aldesleukin therapy. Patients with indwelling central lines are particularly at risk for infection with gram-positive microorganisms. Antibiotic prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin has been associated with a reduced incidence of staphylococcal infections.

Warnings/Precautions

Concerns related to adverse effects:

• Capillary leak syndrome: [US Boxed Warning]: Aldesleukin therapy is associated with capillary leak syndrome (CLS), characterized by vascular tone loss and extravasation of plasma proteins and fluid into extravascular space. CLS results in hypotension and reduced organ perfusion, which may be severe and can result in death. Cardiac arrhythmia (supraventricular and ventricular), angina, myocardial infarction, respiratory insufficiency (requiring intubation), GI bleeding or infarction, renal insufficiency, edema, and mental status changes may also be associated with CLS. CLS onset is immediately after treatment initiation with a concomitant decrease in mean arterial pressure in most patients within 2 to 12 hours after aldesleukin initiation. Monitor BP and heart rate frequently. Monitor fluid status and organ perfusion status carefully; consider fluids and/or pressor agents to maintain organ perfusion. Withhold treatment for signs of organ hypoperfusion, including altered mental status, reduced urine output, systolic BP <90 mm Hg, or cardiac arrhythmia. Once BP is normalized, may consider diuretics for excessive weight gain/edema (particularly if associated with dyspnea due to pulmonary congestion). Recovery from CLS generally begins soon after treatment cessation.

• CNS toxicity: [US Boxed Warning]: Withhold aldesleukin for patients developing moderate to severe lethargy or somnolence; continued treatment may result in coma. Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, sepsis, hypoperfusion, CNS malignancy, and/or CNS toxicity. Aldesleukin may cause seizure; use with extreme caution in patients with seizure disorder. Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment. New neurologic symptoms and lesions have been reported in patients without preexisting evidence of CNS metastases; clinical manifestations may include altered mental status, speech difficulties, cortical blindness, limb or gait ataxia, hallucinations, agitation, obtundation, and coma. Radiological findings may include multiple and occasionally single cortical lesions on MRI (with evidence of demyelination). Symptoms generally improve upon discontinuation; however, cases with permanent damage have been reported.

• GI toxicity: Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011).

• Hyperglycemia: Symptomatic hyperglycemia and/or diabetes mellitus have been reported with aldesleukin.

• Infections: [US Boxed Warning]: Aldesleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting bacterial infections should be adequately treated prior to aldesleukin initiation. Patients with indwelling central lines are particularly at risk for infection with gram-positive microorganisms. Antibiotic prophylaxis has been associated with a reduced incidence of staphylococcal infections. Monitor for signs of infection or sepsis during treatment.

• Thyroid disorders: Thyroid disease (hypothyroidism, biphasic thyroiditis, and thyrotoxicosis) may occur; the onset of hypothyroidism is usually 4 to 17 weeks after treatment initiation; may be reversible upon treatment discontinuation (Hamnvik 2011). Hypothyroidism may sometimes be preceded by hyperthyroidism. Some cases of hypothyroidism required thyroid replacement therapy.

Disease-related concerns:

• Autoimmune/inflammatory disorders: Aldesleukin has been associated with exacerbation or new onset of autoimmune disease or inflammatory disorders. Exacerbation of Crohn disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, and bullous pemphigoid have been reported following aldesleukin monotherapy or combination therapy with interferon.

• Cardiopulmonary disease: [US Boxed Warning]: Treatment with aldesleukin should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease and in patients who are fluid-restricted or where edema may be poorly tolerated. Eosinophilic infiltration of cardiac and pulmonary tissue may occur with aldesleukin. In a scientific statement from the American Heart Association, interleukin-2 has been determined to be an agent that may either cause direct myocardial toxicity (rare) or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hepatic function: Aldesleukin may impair hepatic function; concomitant hepatotoxic agents may increase the risk of hepatotoxicity.

• Renal function: Patients must have a serum creatinine ≤1.5 mg/dL prior to treatment. Aldesleukin may impair renal function; concomitant nephrotoxic agents may increase the risk of renal toxicity.

Special populations:

• Elderly: The incidence of dyspnea and severe urogenital toxicities may be increased in elderly patients.

• Transplant recipients: Enhancement of cellular immune function due to aldesleukin may increase the risk of allograft rejection.

Other warnings/precautions:

• Contrast media: An acute array of symptoms resembling aldesleukin adverse reactions (fever, chills, nausea, rash, pruritus, diarrhea, hypotension, edema, and oliguria) were observed within 1 to 4 hours after iodinated contrast media administration, usually when given within 4 weeks after aldesleukin treatment, although symptoms have been reported several months after aldesleukin treatment.

• Experienced physician: [US Boxed Warning]: Aldesleukin should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.

Monitoring Parameters

Baseline and periodic: CBC with differential and platelets (daily during treatment); blood chemistries, including electrolytes (daily during treatment), renal and hepatic function tests, and chest x-ray (daily during treatment); pulmonary function tests and arterial blood gases (baseline), thallium stress test (prior to treatment). Monitor thyroid function tests (thyroid-stimulating hormone at baseline then every 2 to 3 months during aldesleukin treatment [Hamnvik 2011]).

Monitoring during therapy should include daily (hourly if hypotensive) vital signs (temperature, pulse, BP, and respiration rate), weight, and fluid intake and output; in a patient with a decreased BP, especially systolic BP <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotensive patients should be taken hourly and central venous pressure checked; monitor for change in mental status, and for signs of infection.

Reproductive Considerations

Effective contraception is recommended for males and/or females of reproductive potential using this medication.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat kidney cancer.

• It is used to treat a type of skin cancer (melanoma).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Nausea

• Vomiting

• Anxiety

• Lack of appetite

• Diarrhea

• Weight gain

• Runny nose

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Thyroid problems like change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, trouble focusing, inability handling heat or cold, menstrual changes, tremors, or sweating

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills

• Acidosis like confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Capillary leak syndrome like abnormal heartbeat; chest pain; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; unable to pass urine or change in amount of urine passed; or blood in the urine

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Feeling sluggish

• Severe fatigue

• Severe dizziness

• Passing out

• Mouth sores

• Mouth irritation

• Sensing things that seem real but are not

• Trouble speaking

• Abnormal gait

• Change in balance

• Blindness

• Behavioral changes

• Mood changes

• Seizures

• Bruising

• Bleeding

• Severe loss of strength and energy

• Swelling

• Shortness of breath

• Skin changes

• Skin breakdown

• Blisters

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.