Aldesleukin is an interleukin-2 lymphocyte growth factor. It is FDA approved for the treatment of metastatic malignant melanoma and metastatic renal cell cancer. Treat any pre-existing bacterial infections prior to initiating therapy. Aldesleukin can cause serious and life-threatening Capillary Leak Syndrome (CLS) and should be administered in a hospital setting with an intensive care unit. Serious and potentially permanent neurotoxicity has also been reported with treatment.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Emetic Risk
-Moderate
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Premedicate patients with an antipyretic immediately prior to administration of aldesleukin. Continue antipyretics as needed during treatment for fever.
-Administer prophylactic antibiotics according to institutional guidelines.
-Administer prophylactic medication for GI irritation and bleeding during each aldesleukin treatment course.
-Severe hypersensitivity reactions may occur. Additional medications may be needed if patients experience hypotension, dyspnea, rigors, nausea, diarrhea, pruritus, or dermatitis. Administer aldesleukin in an inpatient hospital setting with an intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine available.
Reconstitution:
-Add 1.2 mL of Sterile Water for Injection to the side of the vial and then gently swirl to avoid excess foaming; do not shake. Do not reconstitute using Bacteriostatic Water for Injection or 0.9% Sodium Chloride Injection.
-The resulting final vial concentration after reconstitution is 18 million International Units (1.1 mg)/mL.
Dilution:
-Use a polyvinyl chloride bag to dilute reconstituted aldesleukin to a concentration between 0.03 mg/mL and 0.07 mg/mL.
-Dilute doses of 25.4 million International Units (1.5 mg)/mL or less in 25 mL of 5% Dextrose Injection.
-Dilute doses greater than 25.4 million International Units (1.5 mg)/mL to 60 million International Units (3.5 mg)/mL in 50 mL of 5% Dextrose Injection.
-Dilute doses greater than 60 million International Units (3.5 mg)/mL in 100 mL of 5% Dextrose Injection.
-Storage following dilution: Diluted aldesleukin may be stored in the refrigerator at 2 to 8 degrees Celsius (36 to 46 degrees Farenheit) for up to 48 hours from the time of preparation to the end of the infusion; do not freeze. Protect from light.
Intravenous infusion:
-Allow the diluted solution to come to room temperature prior to administration.
-Do not use an in-line filter when administering aldesleukin.
-Do not administer other drugs through the same IV line.
-Administer by IV infusion over 15 minutes.
Aldesleukin administration can result in capillary leak syndrome (CLS), a severe and life-threatening syndrome characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. CLS can begin immediately after aldesleukin treatment is initiated, and may cause hypotension, reduced organ perfusion, cardiac arrhythmias, angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes. Aldesleukin is contraindicated in patients with significant cardiac disease (including those with an abnormal ejection fraction, impaired wall motion, or significant coronary artery disease), pulmonary disease (including those with an FEV1 of 2 liters or less, or less than 75% predicted for height and age), or hepatic disease. Aldesleukin administration requires a specialized care setting, such as a hospital or intensive care facility, under the supervision of a qualified clinician. Monitor for signs and symptoms of CLS including vital signs, weight, fluid intake, albumin levels, and urine output. An interruption or discontinuation of therapy is necessary for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, oxygen saturation less than 90%, a fall in systolic blood pressure below 90 mmHg, or onset of cardiac arrhythmias; initiate standard CLS management, which may include intensive care.
Immune-mediated inflammatory arthritis and myositis have been reported with the use of aldesleukin. Myopathy and rhabdomyolysis have also been reported in post-marketing experience.
Cardiovascular disorders including abnormal EKG and congestive heart failure occurred in 11% of patients treated with aldesleukin in a series of single and multicenter controlled studies. Additionally, sinus tachycardia (23%), supraventricular tachycardia (SVT) (12%; grade 4, 1%), ventricular tachycardia (less than 10%; grade 4, 1%), myocardial infarction (less than 10%; grade 4, 1%), arrhythmia (10%), and cardiac arrest (less than 10%; grade 4, 1%) occurred in these trials; grade 4 bradycardia, pericardial effusion, ventricular extrasystoles, acute myocardial ischemia, supraventricular arrhythmia, coronary artery disease, and second degree AV block were reported in fewer than 1% of these patients. Pericarditis occurred in patients treated with aldesleukin-based regimens using doses other than the recommended dose. Immune-mediated myocarditis has also occurred. Cardiomyopathy and cardiac tamponade have been reported in postmarketing experience with aldesleukin. The use of aldesleukin is contraindicated in patients with significant cardiac disease (including those with an abnormal ejection fraction, impaired wall motion, or significant coronary artery disease). An interruption or discontinuation of therapy may be necessary for different arrhythmias, depending on the severity.
Confusion (34%; grade 4, 1%), psychotic disorder (less than 10%; grade 4, 1%), and anxiety (12%) occurred in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 agitation and paranoia were each reported in less than 1% of patients. Severe depression leading to suicidal death occurred in fewer than 1% of patients treated with aldesleukin-based regimens using doses other than the recommended dose. Insomnia has been reported in postmarketing experience with aldesleukin; hallucinations and agitation have also occurred. Permanently discontinue aldesleukin for cases of toxic psychosis lasting more than 48 hours.
Aldesleukin can cause or exacerbate immune-mediated thyroid disorders including thyroiditis. Hypothyroidism, which is sometimes preceded by hyperthyroidism, has also been reported. Evaluate thyroid function at baseline and monitor periodically during treatment. Begin hormone replacement for hypothyroidism or medical management of hyperthyroidism as clinically indicated. Aldesleukin may need to be interrupted or discontinued depending on severity.
Aldesleukin may cause nephrotoxicity. In a series of single and multicenter controlled studies, oliguria (63%; grade 4, 6%), increased serum creatinine (33%; grade 4, 1%), anuria (less than 10%; grade 4, 5%), and acute kidney injury (less than 10%; grade 4, 1%) were reported in patients treated with aldesleukin; grade 4 cases of renal failure and renal tubular necrosis were each reported in less than 1% of patients. Serious cases of allergic nephritis were also reported in patients treated with aldesleukin-based regimens using doses other than the recommended dose. Immune-mediated crescentic IgA glomerulonephritis has also occurred in patients who received aldesleukin. Aldesleukin is contraindicated in patients with significant renal disease; use aldesleukin with caution in patients with pre-existing renal impairment, as treatment can cause serious nephrotoxicity including oliguria and renal failure. The serum creatinine should be 1.5 mg/dL before beginning treatment with aldesleukin. Monitor serum creatinine at baseline and daily throughout each course of therapy. An interruption or discontinuation of therapy is necessary for reduced urine output.
Thrombocytopenia (37%; grade 4, 1%), anemia (29%), and leukopenia (16%) occurred in patients treated with aldesleukin in a series of single and multicenter controlled studies. Aldesleukin can cause impaired neutrophil function (reduced chemotaxis). Additionally, neutropenia, eosinophilia, and lymphopenia were reported in postmarketing experience with aldesleukin. Serious manifestations of eosinophilia involving eosinophilic infiltration of cardiac and pulmonary tissues can also occur after aldesleukin administration.
Diarrhea (67%; grade 4, 2%), vomiting (50%), nausea (35%), stomatitis (22%; grade 4, less than 1%), abdominal pain (11%), and abdominal distention (10%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 GI perforation occurred in fewer than 1% of patients. Serious cases of duodenal ulcer and bowel necrosis were reported in patients treated with aldesleukin-based regimens using doses other than the recommended dose. Immune-mediated colitis and Crohn's disease have also been reported after aldesleukin treatment. Gastritis and GI obstruction have been reported in postmarketing experience with aldesleukin.
Asthenia (23%), malaise (27%), and pain (12%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies.
Hyperbilirubinemia (40%; grade 4, 2%), elevated hepatic enzymes (AST) (23%; grade 4, 1%), and increased alkaline phosphatase (10%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies. Grade 4 abnormal liver function tests and fatal cases of hepatic failure were each reported in less than 1% of patients. Hepatitis, hepatosplenomegaly, and cholecystitis were reported in postmarketing experience with aldesleukin. Treatment with aldesleukin is contraindicated in patients with significant hepatic disease. An interruption or discontinuation of therapy may be necessary depending on the severity of hepatic impairment.
Dyspnea (43%; grade 4, 1%), lung disorders including pulmonary congestion, rales, and rhonchi (24%), respiratory disorders including acute respiratory distress syndrome (ARDS), lung infiltration, respiratory failure, and endotracheal intubation (11%; grade 4, 3%), apnea (less than 10%; grade 4, 1%), cough (11%), and rhinitis (10%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 cases of respiratory acidosis, asthma, hyperventilation, hypoxia, hypoventilation, and pneumothorax were each reported in fewer than 1% of patients. Fatal respiratory arrest and respiratory failure were also reported in fewer than 1% of patients who received aldesleukin. The use of aldesleukin is contraindicated in patients with significant pulmonary disease (including those with an FEV1 of 2 liters or less, or less than 75% predicted for height and age). An interruption or discontinuation of therapy is necessary for oxygen saturation less than 90%.
Rash (42%), pruritus (24%), and exfoliative dermatitis (18%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies. Immune-mediated scleroderma, Stevens-Johnson Syndrome (SJS), and bullous pemphigoid (bullous rash) may occur in patients treated with aldesleukin. Monitor patients for suspected severe skin reactions and exclude other causes. Aldesleukin therapy may need to be interrupted or discontinued depending on the severity of rash.
Hyperglycemia and diabetes mellitus have been reported with aldesleukin therapy. Monitor patients for hyperglycemia and administer insulin as clinically indicated.
Aldesleukin can cause infusion-related reactions including fevers, chills, or rigors, as well as severe hypersensitivity that includes anaphylactoid reactions. Tissue necrosis at the injection site, angioedema, and urticaria were also reported in patients treated with aldesleukin-based regimens using doses other than the recommended dose. Premedicate all patients with an antipyretic during treatment and continue as needed for fever. Permanently discontinue aldesleukin in patients who experience a severe hypersensitivity reaction.
Treatment with aldesleukin is associated with an increased risk of infection. In a series of single and multicenter controlled studies, infection was reported in 13% of patients (grade 4, 1%); sepsis occurred in 1% and grade 4 gangrene and endocarditis each in fewer than 1% of patients. Meningitis was additionally reported in patients treated with aldesleukin-based regimens using doses other than the recommended dose. Pneumonia, endocarditis, and cellulitis were additionally reported in postmarketing experience with aldesleukin. Treat pre-existing infections prior to initiation of aldesleukin therapy. Monitor patients for signs and symptoms of infection; an interruption or discontinuation of therapy may be necessary.
Metabolic acidosis (12%; grade 4, 1%), hypomagnesemia (12%), and hypocalcemia (11%; grade 4, less than 1%) occurred in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 hyperuricemia was reported in less than 1% of patients. Hyponatremia and hypophosphatemia were additionally reported in postmarketing experience with aldesleukin.
Antibody formation has been reported in patients receiving aldesleukin. In clinical trials, low titers of anti-aldesleukin antibodies have been reported in 66% and 74% of metastatic melanoma and renal cell carcinoma patients, respectively. In one study, 11 of 13 patients developed anti-aldesleukin antibodies by day 15 after the first cycle of aldesleukin therapy. One patient developed neutralizing antibodies. The clinical significance of antibody formation is not known, but the mean systemic exposure (AUC) was increased by 68% among the patients who had anti-aldesleukin antibodies as compared with no change in AUC among the 2 antibody-negative patients.
Grade 4 cases of pneumothorax occurred in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Grade 4 cases of pulmonary edema occurred in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Grade 4 cases of bleeding, hematemesis, hemorrhagic diarrhea, hemoptysis, and GI bleeding were each reported in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies. Retroperitoneal bleeding and intracranial bleeding including subdural hemorrhage, subarachnoid hemorrhage and cerebral hemorrhage have been reported in postmarketing experience with aldesleukin.
Disseminated intravascular coagulation (DIC) occurred in fewer than 10% of patients treated with aldesleukin in a series of single and multicenter controlled studies (grade 4, 1%); grade 4 cases of thrombosis occurred in fewer than 1% of patients. Fatal pulmonary embolism occurred in fewer than 1% of patients who received aldesleukin-based regimens using does other than the recommended dose.
Decreased appetite or anorexia was reported in 20% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Weight gain occurred in 16% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Grade 4 pancreatitis was reported in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Tracheoesophageal fistula was reported in patients treated with aldesleukin-based regimens using doses other than the recommended dose.
Chills (52%) and fever (29%; grade 4, 1%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 hypothermia was reported in less than 1% of patients. Fatal cases of malignant hyperthermia occurred in fewer than 1% of patients who received aldesleukin-based regimens using doses other than the recommended dose. Neutropenic fever has been reported in postmarketing experience with aldesleukin.
Peripheral edema (28%) and generalized edema (15%) were reported in patients treated with aldesleukin in a series of single and multicenter controlled studies.
Hypotension (71%; grade 4, 3%) and peripheral vasodilation (13%) occurred in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 blood pressure fluctuations were reported in 1% and grade 4 hypertension in fewer than 1% of patients. An interruption or discontinuation of therapy is necessary for a fall in systolic blood pressure below 90 mmHg.
Grade 4 cases of phlebitis were reported in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies.
Aldesleukin can cause neurotoxicity which may be permanent, including mental status changes, speech difficulties, limb or gait ataxia, obtundation, demyelinating polyneuropathy, and coma; alterations in mental status may progress for several days before recovery begins. Multiple and, less commonly, single cortical lesions have been observed on MRI along with evidence of demyelination; once case of possible cerebral vasculitis has been reported. Stupor (less than 10%; grade 4, 1%), coma (less than 10%; grade 4, 2%), somnolence (22%), and dizziness (11%) occurred in patients treated with aldesleukin in a series of single and multicenter controlled studies; grade 4 cerebral edema, peripheral neuropathy, seizures, and syncope occurred in less than 1% of patients. Encephalopathy, extrapyramidal disorder, and neuralgia have been reported in postmarketing experience with aldesleukin. Immune-mediated neuritis has also been reported. Aldesleukin is contraindicated in patients with significant CNS impairment; avoid the use of aldesleukin in patients with seizure disorder or a history of seizures, or abnormal intracranial imaging. Use aldesleukin with caution in patients who have a history of neurological disease. Evaluate and treat CNS metastases prior to initiation of aldesleukin therapy. Monitor patients for signs and symptoms of neurotoxicity during aldesleukin treatment. An interruption of therapy is necessary for patients who develop moderate to severe lethargy or somnolence as continued administration may result in coma. Permanently discontinue aldesleukin for coma lasting more than 48 hours or for repetitive or difficult to control seizures.
Mydriasis and a pupillary disorder were each reported in fewer than 1% of patients treated with aldesleukin in a series of single and multicenter controlled studies. Immune-mediated oculo-bulbar myasthenia gravis and optic neuritis resulting in blindness has also been reported with aldesleukin treatment.
Treatment with aldesleukin may increase the risk of organ transplant rejection; aldesleukin is contraindicated in patients with organ allografts.
Immune-mediated reactions which may be severe or fatal can occur in any organ system or tissue during treatment with aldesleukin. Exacerbation of pre-existing autoimmune disease or newly diagnosed autoimmune disease including cerebral vasculitis, cholecystitis, crescentic IgA glomerulonephritis, inflammatory arthritis, myocarditis, myositis, and scleroderma have been reported. Aldesleukin therapy may need to be interrupted or discontinued depending on severity of the reaction.
Patients with known or suspected bacterial infection should be adequately treated before initiating treatment with aldesleukin. Consider antibiotic prophylaxis in patients with indwelling central lines (central venous catheter placement). Aldesleukin can cause impaired neutrophil function and an increased risk of disseminated infection including sepsis and endocarditis. Monitor patients for signs and symptoms of infection; an interruption or discontinuation of therapy may be necessary.
Aldesleukin is contraindicated in patients with significant cardiac disease (including those with an abnormal ejection fraction, impaired wall motion, or significant coronary artery disease), pulmonary disease (including those with an FEV1 of 2 liters or less, or less than 75% predicted for height and age), or hepatic disease. Aldesleukin administration requires a specialized care setting, such as a hospital or intensive care facility, under the supervision of a qualified clinician. Aldesleukin therapy requires an experienced clinician knowledgeable in the use of anticancer agents and specialists skilled in cardiopulmonary or intensive care medicine must be available. 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. The potentially fatal syndrome may cause hypotension, reduced organ perfusion, cardiac arrhythmias, angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes. Avoid concomitant use of aldesleukin with other products known to cause hypotension including antihypertensive drugs, nephrotoxic drugs, and hepatotoxic drugs. Monitor for signs and symptoms of CLS including vital signs, weight, fluid intake, albumin levels, and urine output. An interruption or discontinuation of therapy is necessary for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, oxygen saturation less than 90%, a fall in systolic blood pressure below 90 mmHg, or onset of cardiac arrhythmias; initiate standard CLS management, which may include intensive care.
Immune-mediated colitis has been reported with aldesleukin therapy. Use aldesleukin with caution in patients with pre-existing inflammatory bowel disease such as ulcerative colitis or Crohn's disease. Monitor patients for symptoms of colitis (e.g., diarrhea, severe abdominal pain). Aldesleukin therapy may need to be interrupted or discontinued depending on severity.
Immune-mediated serious rash including Stevens-Johnson Syndrome (SJS) and bullous pemphigoid may occur in patients treated with aldesleukin. Monitor patients for suspected severe skin reactions and exclude other causes. Aldesleukin therapy may need to be interrupted or discontinued depending on the severity of rash.
Aldesleukin can cause immune-mediated thyroid disorders. Evaluate thyroid function at baseline and monitor periodically during treatment. Begin hormone replacement for hypothyroidism or medical management of hyperthyroidism as clinically indicated. Aldesleukin may need to be interrupted or discontinued depending on severity.
Aldesleukin is contraindicated in patients with organ transplant allografts. Aldesleukin may increase the risk of allograft rejection in transplant patients.
Hyperglycemia and diabetes mellitus have been reported with aldesleukin therapy. Monitor patients for hyperglycemia and administer insulin as clinically indicated.
Aldesleukin is contraindicated in patients with significant CNS impairment; avoid the use of aldesleukin in patients with seizure disorder or a history of seizures, or abnormal intracranial imaging. Use aldesleukin with caution in patients who have a history of neurological disease. Evaluate and treat CNS metastases prior to initiation of aldesleukin therapy. Avoid the use of aldesleukin with other potential neurotoxic agents if possible. Aldesleukin can cause neurotoxicity which may be permanent, including mental status changes, speech difficulties, cortical blindness, limb or gait ataxia, hallucinations, agitation, obtundation, demyelinating polyneuropathy, and coma. Immune-mediated oculo-bulbar myasthenia gravis and neuritis, including optic neuritis resulting in blindness, has been reported with aldesleukin treatment. Monitor patients for signs and symptoms of neurotoxicity during aldesleukin treatment. An interruption of therapy is necessary for patients who develop moderate to severe lethargy or somnolence as continued administration may result in coma. Permanently discontinue aldesleukin for coma or toxic psychosis lasting more than 48 hours or for repetitive or difficult to control seizures.
Aldesleukin is contraindicated in patients with significant renal disease; use aldesleukin with caution in patients with pre-existing renal impairment, as treatment can cause serious nephrotoxicity including oliguria and renal failure. The serum creatinine (SCr) should be 1.5 mg/dL or less prior to beginning therapy. Avoid concomitant use of other nephrotoxic agents during treatment if possible. Monitor SCr at baseline and daily throughout each course of therapy; an interruption or discontinuation of therapy may be necessary depending on the severity of renal impairment.
Radiographic contrast administration may result in delayed reactions in patients who are receiving or have received treatment with aldesleukin. These reactions typically occur within 1 to 4 hours after administration of iodinated contrast media and are most likely when iodinated contrast media is given within 4 weeks after the last dose of aldesleukin; however, delayed reactions have also been reported to occur when contrast media was given several months after aldesleukin treatment.
Aldesleukin can cause infusion-related reactions including fevers, chills, or rigors, as well as severe hypersensitivity reactions that include anaphylaxis. Premedicate all patients with an antipyretic during treatment and continue as needed for fever. Permanently discontinue aldesleukin in patients who experience a severe hypersensitivity reaction.
Pregnancy should be avoided by females of reproductive potential during aldesleukin treatment. Although there are no adequately controlled studies in pregnant women, aldesleukin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Intravenous administration of aldesleukin to pregnant rats during organogenesis resulted in embryo-lethality at exposures 27 times that in humans at the recommended dose; maternal toxicities were observed at exposures 2.1 times the human exposure at the recommended dose. Additionally, capillary leak syndrome in females who are exposed to aldesleukin during pregnancy may result in maternal hypotension and decreased placental perfusion, which can lead to intrauterine growth restriction, perinatal asphyxia, or fetal/neonatal demise. Women who are pregnant or who become pregnant while receiving aldesleukin should be apprised of the potential hazard to the fetus. Monitor fetal and neonatal status in pregnant women who develop aldesleukin-associated capillary leak syndrome.
Counsel patients about the reproductive risk and contraception requirements during aldesleukin treatment. Aldesleukin can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during treatment with aldesleukin. Females of reproductive potential should undergo pregnancy testing prior to initiation of aldesleukin. Women who become pregnant while receiving aldesleukin should be apprised of the potential hazard to the fetus.
Due to the potential for serious adverse reactions in nursing infants from aldesleukin including impaired immune function, advise women to discontinue breast-feeding during treatment. It is not known whether aldesleukin is present in human milk, although maternal cytokines are known to be present in human milk.
For the treatment of malignant melanoma:
-for the treatment of metastatic malignant melanoma:
NOTE: Aldesleukin has been designated an orphan drug by the FDA for the treatment of metastatic melanoma.
Intravenous dosage:
Adults: 600,000 International Units/kg (0.037 mg/kg) IV every 8 hours on days 1 through 5 (maximum, 14 doses) and days 15 through 19 (maximum, 14 doses); in all, there are a maximum of 28 doses per treatment course. Premedicate patients with an antipyretic. Evaluate patients for response approximately 4 weeks after completion of this cycle and again immediately prior to the scheduled start of the next cycle; each cycle should be separated by a rest period of at least 7 weeks from the date of hospital discharge. Treatment with aldesleukin resulted in an objective response rate of 16% (complete response, 6%) for a median of 9 months in patients with metastatic melanoma across 8 clinical trials (n = 270); not all patients in these studies received the recommended aldesleukin dosing regimen.
For the treatment of acute myelogenous leukemia (AML)*:
NOTE: Aldesleukin has been designated an orphan drug by the FDA for this indication.
-for consolidation treatment in patients with AML following chemotherapy or autologous bone marrow transplantation*:
Intravenous dosage:
Adults: At time of review, evidence does not support the use of aldesleukin for this indication. As consolidation therapy, patients who achieved second remission following standard induction chemotherapy or autologous BMT received aldesleukin (IL-2) 9 million International Units/m2 per day IV over 1 hour on days 1 through 5 and days 8 through 12 every 6 weeks, up to a maximum of 4 cycles. The median duration of disease-free survival was 11 (4 to 49+) months. In 24% of patients treated with IL-2, the duration of the second remission is greater than that of the first. Another study using different doses of IL-2 has been reported in AML and acute lymphocytic leukemia (ALL) patients following autologous BMT in first remission. In this study, the aldesleukin dosage was given at doses of 12, 16, 20, and 24 million International Units/m2 per day as a continuous IV infusion for 5 cycles (cycle 1: 5 days, then cycles 2 through 5: 2 days starting on days 15, 29, 43, 57). Although aldesleukin therapy increased immune stimulation, it was not associated with increases in disease-free survival in these patients.
Children: At time of review, evidence does not support the use of aldesleukin for this indication. In a phase 3 clinical trial, 289 patients (ages 1 day to 20 years of age) with AML were randomized to receive a single course of aldesleukin, IL-2 (9 million International Units/m2 per day continuous IV infusion on days 0 through 3 and 1.6 million International Units/m2 per day continuous IV infusion on days 8 through 17) or no additional therapy after treatment that included induction, consolidation, and further chemotherapy intensification. The primary endpoint, disease-free survival, and overall survival were not significantly different between the 2 treatment arms.
-for treatment of relapsed or refractory AML*:
Intravenous dosage:
Adults: 8 million International Units/m2 IV via bolus infusion was given every 8 hours during cycle 1 (days 1 through 5) and every 12 hours during cycles 2 (days 15 through 19) and 3 (days 29 through 33) in a phase 2 study of 49 patients with relapsed or refractory acute leukemia (30 AML, 19 ALL). Although immune activation was observed (increased circulating T-cells and NK-cells; increased LAK cytotoxic activity), tumor response was only 7% among patients with AML. Grade 4 neutropenia occurred in 46% of patients and grade 4 thrombocytopenia occurred in 84% of patients during therapy.
For the treatment of cutaneous T-cell lymphoma (CTCL)* including mycosis fungoides* and Sezary Syndrome*:
Intravenous dosage:
Adults: 20 million International Units/m2 per day continuous IV infusion for 3 courses of 5, 4, and 3 days on weeks 1, 3, and 5, respectively, has been studied. After evaluation, a monthly maintenance treatment of IL-2 20 million International Units/m2 per day continuous IV infusion for 5 days was optional. If the patient developed grade 3 toxicity, the infusion was held until parameters returned to baseline or grade 1 toxicity, and then treatment was resumed at the same dose. The dose was reduced to 10 million International Units/m2 per day in case of subsequent grade 3 toxicity. Treatment was stopped if the patient developed grade IV toxicity. Of the patients with mycosis fungoides and/or Sezary syndrome, 5 of 7 patients responded, including one CR, and one patient had stable disease.
Subcutaneous dosage:
Adults: 20 million International Units/m2 per day subcutaneously on days 1 through 5 (week 1), days 1 through 4 (week 3), and days 1 through 3 (week 5); after evaluation, maintenance doses of 20 million International Units/m2 per day subcutaneously on days 1 through 5 once monthly were optional. In a phase II clinical trial of 22 patients with relapsed or refractory mycosis fungoides and/or Sezary syndrome, interleukin-2 (IL-2) produced an overall response rate of 18% (all partial responses). The median time to response was 4 months.
For the treatment of leprosy (Hansen's disease)*:
Intradermal dosage*:
Adults: 180,000 International Units via intradermal injection into each lesion twice daily for 8 days.
For the treatment of steroid-refractory chronic graft-versus-host disease (GVHD)*:
Subcutaneous dosage:
Adults: 1 million International Units/m2 subcutaneously once daily.
Children and Adolescents 2 to 17 years: 1 million International Units/m2 subcutaneously once daily.
For the treatment of renal cell cancer:
-for the treatment of metastatic renal cell cancer:
NOTE: Aldesleukin has been designated an orphan drug by the FDA for the treatment of metastatic renal cell cancer.
Intravenous dosage:
Adults: 600,000 International Units/kg (0.037 mg/kg) IV every 8 hours on days 1 through 5 (maximum, 14 doses) and days 15 through 19 (maximum, 14 doses); in all, there are a maximum of 28 doses per treatment course. Premedicate patients with an antipyretic. Evaluate patients for response approximately 4 weeks after completion of this cycle and again immediately prior to the scheduled start of the next cycle; each cycle should be separated by a rest period of at least 7 weeks from the date of hospital discharge. Treatment with aldesleukin resulted in an objective response rate of 15% (complete response, 7%) for a median of 54 months in patients with metastatic renal cell cancer across 7 clinical trials (n = 255); not all patients in these studies received the recommended aldesleukin dosing regimen.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities:
-In general, dosage adjustments are not recommended for adverse reactions; an interruption or discontinuation of therapy is recommended based on the severity of the adverse reaction.
Cardiovascular
-Atrial fibrillation, supraventricular tachycardia, bradycardia that requires treatment or is recurrent/persistent, or a decrease in systolic blood pressure below 90 mmHg: Interrupt aldesleukin therapy. When the patient is asymptomatic with full recovery to normal sinus rhythm, therapy may be resumed.
-Sustained ventricular tachycardia (5 beats or more), cardiac rhythm disturbances that are not controlled or are unresponsive to management, ECG changes consistent with ischemia or myocardial infarction or angina/chest pain, cardiac tamponade: Permanently discontinue therapy.
Dermatologic
-Bullous dermatitis or marked worsening of pre-existing skin condition: Interrupt aldesleukin therapy. When all signs of bullous dermatitis have resolved, therapy may be resumed.
Gastrointestinal
-Fecal immunochemical test (FIT) or fecal occult blood test (FOBT) positive: Interrupt aldesleukin therapy. When FIT or FOBT is negative, therapy may be resumed.
-Bowel ischemia/perforation or GI bleeding requiring surgery: Permanently discontinue therapy.
Infection
-Sepsis syndrome, patient is clinically unstable: Interrupt aldesleukin therapy. When sepsis syndrome has resolved, the patient is clinically stable, and the infection is under treatment, therapy may be resumed.
Neurologic
-Mental status changes, including moderate confusion or agitation: Interrupt aldesleukin therapy. When symptoms are completely resolved, therapy may be resumed.
-Coma or toxic psychosis lasting more than 48 hours, or repetitive or difficult to control seizures: Permanently discontinue therapy.
Respiratory
-O2 saturation less than 90%: Interrupt aldesleukin therapy. When O2 saturation is greater than 90%, therapy may be resumed.
-Intubation for more than 72 hours: Permanently discontinue therapy.
Maximum Dosage Limits:
-Adults
600,000 International Units/kg (0.037 mg/kg) IV every 8 hours.
-Geriatric
600,000 International Units/kg (0.037 mg/kg) IV every 8 hours.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Hepatotoxicity
-Signs of hepatotoxicity including liver pain or grade 3 or higher AST or ALT elevation: Hold all further aldesleukin doses for that course. A new course of treatment may be initiated no sooner than 7 weeks after signs of hepatotoxicity have resolved and the patient has been discharged from the hospital.
-Hepatic failure: Permanently discontinue therapy.
Patients with Renal Impairment Dosing
Nephrotoxicity
-Serum creatinine (SCr) greater than 4.5 mg/dL, or SCr of 4 mg/dL or more in the presence of severe volume overload, acidosis, or hyperkalemia: Interrupt aldesleukin therapy. When the SCr returns to less than 1.5 mg/dL or baseline, and fluid and electrolyte status is stable, therapy may be resumed.
-Persistent oliguria, urine output less than 10 mL/hour for 16 to 24 hours with rising SCr: Interrupt aldesleukin therapy. When urine output is greater than 10 mL/hour with a decrease in SCr greater than 1.5 mg/dL or normalization of SCr, therapy may be resumed.
-Renal failure requiring dialysis for more than 72 hours: Permanently discontinue therapy.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Acyclovir: (Major) Avoid concomitant use of acyclovir and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Adefovir: (Major) Avoid concomitant use of adefovir dipivoxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Albuterol; Budesonide: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Amikacin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aminoglycosides: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amlodipine; Celecoxib: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Amphotericin B lipid complex (ABLC): (Major) Avoid concomitant use of amphotericin B and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amphotericin B liposomal (LAmB): (Major) Avoid concomitant use of amphotericin B and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amphotericin B: (Major) Avoid concomitant use of amphotericin B and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Azelastine; Fluticasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Beclomethasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Betamethasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Budesonide: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Budesonide; Formoterol: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Bupivacaine; Meloxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Capecitabine: (Major) Avoid concomitant use of capecitabine and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Carboplatin: (Major) Avoid concomitant use of carboplatin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Celecoxib: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Celecoxib; Tramadol: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ciclesonide: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Cidofovir: (Contraindicated) Concomitant use of cidofovir and aldesleukin is contraindicated due to the increased risk of nephrotoxicity.
Cisplatin: (Major) Avoid concomitant use of cisplatin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clindamycin: (Major) Avoid concomitant use of clindamycin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Corticosteroids: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Cortisone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Cyclosporine: (Major) Avoid concomitant use of cyclosporine and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Deferasirox: (Major) Avoid concomitant use of deferasirox and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Deflazacort: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Dexamethasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Dichlorphenamide: (Moderate) Use dichlorphenamide and aldesleukin, IL-2 together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diclofenac; Misoprostol: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diflunisal: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diphenhydramine; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diphenhydramine; Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ethiodized Oil: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Etodolac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fenoprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fludrocortisone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Flunisolide: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Flurbiprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fluticasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Fluticasone; Salmeterol: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Fluticasone; Umeclidinium; Vilanterol: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Fluticasone; Vilanterol: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Formoterol; Mometasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Foscarnet: (Major) Avoid concomitant use of foscarnet and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ganciclovir: (Major) Avoid concomitant use of ganciclovir and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Gentamicin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Hydrocodone; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Hydrocortisone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ibuprofen; Famotidine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ibuprofen; Oxycodone: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ibuprofen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Indinavir: (Moderate) In HIV-positive patients treated with aldesleukin, IL-2, and indinavir, the plasma AUC levels of indinavir increased 88% in 8 of 9 patients. The clearance of indinavir was decreased by 56% by day 5 of concurrent therapy. Treatment with IL-2 increased plasma levels of interleukin-6, which is an inhibitor of cytochrome P450 3A4, by 20-fold in these patients. Increased IL-6 levels may have inhibited CYP3A4, resulting in decreased clearance and increased serum levels of indinavir.
Indomethacin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Iodixanol: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Iohexol: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Iomeprol: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Ionic Contrast Media: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Iopamidol: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Iopromide: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Ioversol: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Isosulfan Blue: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Ketoprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ketorolac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Mannitol: (Major) Avoid concomitant use of mannitol and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Meclofenamate Sodium: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Mefenamic Acid: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Meloxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Mesalamine, 5-ASA: (Major) Avoid concomitant use of mesalamine and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Methotrexate: (Moderate) The safety and efficacy of aldesleukin, IL-2 in combination with chemotherapy agents have not been established; however, concurrent or sequential use of these agents is common but results in various pharmacodynamic drug interaction risks. Aldesleukin is associated with serious adverse reactions affecting many organ systems. Concurrent administration of antineoplastic agents possessing nephrotoxic, myelotoxic, or hepatotoxic effects (e.g., methotrexate), may increase toxicity in these organ systems.
Methylprednisolone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Mometasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Nabumetone: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Naproxen; Esomeprazole: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Naproxen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Nefazodone: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing hepatotoxic effects with Aldesleukin, such as nefazodone, may increase the risk of liver dysfunction. In addition, reduced liver function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Neomycin: (Major) Avoid concomitant use of neomycin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Non-Ionic Contrast Media: (Moderate) Monitor patients for delayed aldesleukin "recall" reactions in patients receiving iodinated contrast media after aldesleukin therapy. Symptom onset is typically from 1 to 4 hours after administration of iodinated contrast media and may resemble aldesleukin-related infusion reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. While most common when contrast media is given within 4 weeks of the last dose of aldesleukin, reports have also occurred when contrast media was administered several months after aldesleukin treatment.
Nonsteroidal antiinflammatory drugs: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Olopatadine; Mometasone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Oxaprozin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Pamidronate: (Major) Avoid concomitant use of pamidronate and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Paromomycin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Pentamidine: (Major) Avoid concomitant use of pentamidine and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Piroxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Plazomicin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Prednisolone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Prednisone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Streptomycin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Streptozocin: (Major) Avoid concomitant use of streptozocin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Sulindac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Sumatriptan; Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Tacrolimus: (Major) Avoid concomitant use of tacrolimus and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Telavancin: (Major) Avoid concomitant use of telavancin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tenofovir Alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tenofovir Alafenamide: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tobramycin: (Major) Avoid concomitant use of aminoglycosides and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tolmetin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Triamcinolone: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valacyclovir: (Major) Avoid concomitant use of valacyclovir and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Valganciclovir: (Major) Avoid concomitant use of valganciclovir and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Vancomycin: (Major) Avoid concomitant use of vancomycin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Voclosporin: (Major) Avoid concomitant use of voclosporin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Zoledronic Acid: (Major) Avoid concomitant use of zoledronic acid and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aldesleukin is an interleukin-2 (IL-2) lymphocyte growth factor. Its antitumor activity has not been fully characterized, although in vitro studies on human cell lines have shown enhancement of lymphocyte mitogenesis and cytotoxicity, induction of killer cell activity (lymphokine-activated killer [LAK] and natural killer [NK] cells); interferon gamma production; and proliferation of human IL-2-dependent cell lines. Administration in animals and humans results in many dose-dependent immunologic effects including activation of cellular immunity with lymphocytosis, eosinophilia, thrombocytopenia, 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.
Aldesleukin is administered parenterally. After administration, it is rapidly distributed into the extravascular space with a distribution half-life of 13 minutes. The serum elimination half-life in patients with cancer is 85 minutes when administered as a 5-minute IV infusion; the mean clearance is 268 mL/minute. Aldesleukin is primarily renally excreted by both glomerular filtration and peritubular extraction; it is metabolized in the kidney and excreted into the urine with little to no unchanged drug.
Affected cytochrome P450 isoenzymes: CYP3A
Aldesleukin is metabolized to amino acids in the proximal convoluted tubules of the kidney. It is an inhibitor of the CYP3A isoenzyme subfamily.
-Route-Specific Pharmacokinetics
Intravenous Route
Aldesleukin serum concentrations change proportionally with dose.
-Special Populations
Other
Antibody Formation
Following the first cycle of aldesleukin therapy, the geometric mean exposure (AUC) at day 15 was increased by an average of 68% compared with the day 1 AUC in 11 patients who developed anti-aldesleukin antibodies; no AUC value change was observed between day 1 and day 15 in 2 antibody-negative patients.