Proleukin
Aldesleukin · Injection, Powder, Lyophilized, For Solution · Intravenous
Uses
Proleukin is a lymphocyte growth factor indicated for: The treatment of adults with metastatic renal cell carcinoma. ( 1.1 ) The treatment of adults with metastatic melanoma. ( 1.2 ) 1.1 Metastatic Renal Cell Carcinoma Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma (RCC). 1.2 Metastatic Melanoma Proleukin is indicated for the treatment of adults with metastatic melanoma.
Dosage and administration
Administer Proleukin in an inpatient hospital setting with an intensive care facility. Evaluate cardiovascular, pulmonary, neurologic and renal function before beginning Proleukin. ( 2.1 ) See Full Prescribing Information for Premedication and Supportive medications. ( 2.3 ) Recommended dosage: 600,000 IU/kg (0.037 mg/kg) every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Following 9 days of rest, repeat the schedule for a maximum of another 14 doses (total of 28 doses per course, as tolerated). ( 2.2 ) Evaluate patients approximately 4 weeks after completion of a course of therapy and again immediately prior to the start of the next course. ( 2.2 ) Dose modification for toxicity should be accomplished by withholding or interrupting a dose. ( 2.4 ) Follow reconstitution and dilution procedures. ( 2.5 ) 2.1 Recommended Evaluation and Testing Before Initiating Proleukin Conduct baseline hematologic, chemistry, renal and hepatic function tests. Additionally, evaluate cardiac ejection fraction, coronary artery disease as appropriate, pulmonary function with PFTs, and evaluate for renal, hepatic, and CNS impairment prior to initiating treatment with Proleukin [see Contraindications (4) , Warnings and Precautions (5.1 , 5.2) ]. Verify pregnancy status of females of reproductive potential prior to initiating Proleukin [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ]. 2.2 Recommended Dosage Administer Proleukin in an inpatient hospital setting. An intensive care facility with specialists skilled in cardiopulmonary or intensive care medicine must be available [see Warnings and Precautions (5.1) ] . The recommended dosage of Proleukin for metastatic renal cell carcinoma and metastatic melanoma is described in Table 1. Administer Proleukin as an intravenous infusion after dilution [see Dosage and Administration (2.5) ] . Administer pre-infusion medications and supportive treatment, as appropriate, prior to and during each infusion [see Dosage and Administration (2.3) ]. Discontinue Proleukin for unacceptable toxicity [see Dosage and Administration (2.4) ]. Table 1: Recommended Dosage of Proleukin Each course of therapy consists of the following: Cycle 1 Days 1-5 600,000 IU/kg (0.037 mg/kg) every 8 hours; maximum of 14 doses A maximum of 28 doses (2 cycles) per treatment course Rest period Days 6-14 Cycle 2 Days 15-19 600,000 IU/kg (0.037 mg/kg) every 8 hours; maximum of 14 doses Evaluate patients for response approximately 4 weeks after completion of a course of therapy and again immediately prior to the scheduled start of the next treatment course. Additional courses of treatment may be administered to patients if there is a treatment response following the last course, and the patient did not experience any adverse reactions in previous course(s) that led to permanent discontinuation [see Dosage and Administration (2.4) ]. Separate each treatment course by a rest period of at least 7 weeks from the date of hospital discharge. 2.3 Premedication and Supportive Medications Premedicate patients with an antipyretic immediately prior to beginning Proleukin. Continue antipyretics during treatment as needed for fever [see Warnings and Precautions (5.1 , 5.10) ]. Administer prophylactic antibiotics per institutional guidelines prior to beginning Proleukin and throughout the treatment course for patients with indwelling central catheters [see Warnings and Precautions (5.3) ]. Administer prophylactic medication for gastrointestinal irritation and bleeding during each Proleukin treatment course [see Adverse Reactions (6.1) ]. Additional medications may be needed if patients experience hypotension, dyspnea, rigors, nausea, diarrhea, pruritis, or dermatitis [see Warnings and Precautions (5.1 , 5.8 , 5.9) ]. 2.4 Dosage Modifications for Adverse Reactions No dose reduction for Proleukin is recommended for adverse reactions. In general, withhold or interrupt a dose or permanently discontinue Proleukin based on the severity of the adverse reaction as described in Table 2. Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Cardiovascular [see Warnings and Precautions (5.1) ] Atrial fibrillation, Supraventricular tachycardia, or Bradycardia that requires treatment or is recurrent or persistent Decrease in systolic blood pressure to <90 mmHg Withhold until patient is asymptomatic with full recovery to normal sinus rhythm Sustained ventricular tachycardia (≥5 beats) Cardiac rhythm disturbances not controlled or unresponsive to management ECG changes consistent with ischemia or myocardial infarction or angina/chest pain Cardiac tamponade Permanently discontinue Respiratory [see Warnings and Precautions (5.1) ] O2 saturation <90% Withhold until O2 saturation is >90% Intubation for >72 hours Permanently discontinue Neurologic [see Warnings and Precautions (5.2) ] Mental status changes, including moderate confusion or agitation Withhold until completely resolved Coma or toxic psychosis lasting >48 hours Repetitive or difficult to control seizures Permanently discontinue Gastrointestinal [see Warnings and Precautions (5.1) ] Fecal immunochemical test (FIT) or fecal occult blood test (FOBT) positive Withhold until FIT or FOBT negative Bowel ischemia/perforation or GI bleeding requiring surgery Permanently discontinue Hepatic [see Warnings and Precautions (5.1) ] Signs of hepatic toxicity including liver pain or ≥ Grade 3 AST or ALT elevation Withhold all further treatment for that course.
Dosage forms and strengths
For Injection: 22 million International Units (1.3 mg) of aldesleukin available as a white to off-white, lyophilized powder in a single-dose vial for reconstitution. When reconstituted, each mL contains 18 million International Units (1.1 mg) aldesleukin. For Injection: 22 million International Units (1.3 mg) lyophilized powder in a single-dose vial. ( 3 )
Contraindications
Severe Hypersensitivity Reactions Proleukin is contraindicated in patients with a known history of severe hypersensitivity to aldesleukin or any component of the Proleukin formulation [see Adverse Reactions (6.2) ]. Organ Allografts Proleukin is contraindicated in patients with organ allografts [see Warnings and Precautions (5.5) ] . Significant Organ Impairment Proleukin is contraindicated in patients with significant cardiac (including those with an abnormal cardiac ejection fraction, impaired wall motion, or significant coronary artery disease), pulmonary (including those with an FEV1 ≤ 2 liters or < 75% predicted for height and age), renal, hepatic, or CNS impairment [see Warnings and Precautions (5.1 , 5.2 , 5.4) ] . Hypersensitivity to aldesleukin. ( 4 ) Organ allografts. ( 4 ) Significant organ impairment. ( 4 )
Warnings and precautions
Renal Toxicity: Monitor renal function at baseline and throughout treatment. Withhold Proleukin or permanently discontinue, based on severity. ( 2.4 , 5.4 ) Immune-mediated Adverse Reactions: Exacerbation of pre-existing autoimmune disease or initial presentation of autoimmune and inflammatory disorders can occur in any system or tissue. Proleukin may increase the risk of allograft rejection in transplant patients. Monitor patients and treat as indicated. ( 5.5 ) Severe Hypersensitivity Reaction: Permanently discontinue Proleukin for severe hypersensitivity reactions. ( 4 , 5.9 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Capillary Leak Syndrome Severe and life-threatening capillary leak syndrome (CLS) characterized by hypotension, dyspnea, edema, and hypoalbuminemia can occur with Proleukin, and can result in end organ toxicity including cardiac, respiratory, renal, hepatic toxicity, or death. Do not administer Proleukin to patients with significant cardiac, pulmonary, renal, or hepatic impairment. Avoid concomitant use of Proleukin with other products known to cause hypotension including antihypertensive drugs, those that cause renal toxicity, or hepatotoxicity. CLS may begin immediately after Proleukin treatment is initiated. Monitor for signs and symptoms of CLS including assessments of vital signs, weight, fluid intake, albumin levels and urine output. Withhold or discontinue Proleukin for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, oxygen saturation <90%, a fall in the systolic blood pressure below 90 mm Hg, or onset of cardiac arrhythmias. Initiate standard management for CLS, which may include intensive care [see Dosage and Administration (2.4) , Use in Specific Populations (8.1) ] . 5.2 Neurologic Toxicity Proleukin can cause neurologic toxicities including mental status changes, speech difficulties, cortical blindness, limb or gait ataxia, hallucinations, agitation, obtundation, demyelinating polyneuropathy, and coma. Alterations in mental status may progress for several days before recovery begins. Permanent neurologic deficits have occurred. Radiological findings included multiple and, less commonly, single cortical lesions on MRI and evidence of demyelination. One case of possible cerebral vasculitis has been reported. Monitor patients for signs and symptoms of neurological toxicity during Proleukin treatment. Withhold Proleukin in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma. Permanently discontinue Proleukin for coma or toxic psychosis lasting >48 hours or for repetitive or difficult to control seizures [see Dosage and Administration (2.4) ]. Evaluate and treat CNS metastases prior to initiation of Proleukin. If possible, avoid concomitant use of Proleukin with other product(s) with a known potential to cause neurotoxicity, and avoid Proleukin in patients with seizure disorders or abnormal intracranial imaging [see Contraindications (4) , Adverse Reactions (6.1 , 6.2) ] . Concomitant use of Proleukin with other products that cause neurotoxicity may result in a greater risk of severe neurotoxicity. 5.3 Serious Infections Including Sepsis Proleukin can cause impaired neutrophil function (reduced chemotaxis) and an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Treat pre-existing bacterial infections prior to initiating Proleukin. Consider antibiotic prophylaxis in patients with indwelling central lines. Monitor patients for the development of signs and symptoms of infection during treatment and withhold Proleukin based on severity [see Dosage and Administration (2.4) ]. 5.4 Renal Toxicity Serious renal toxicity, including oliguria and renal failure can occur with Proleukin [see Adverse Reactions (6.1 , 6.2) ] . Pre-existing renal impairment or coadministration of Proleukin with other products known to cause renal toxicity may increase this risk. If possible, avoid concomitant use of Proleukin with other product(s) with a known potential to cause renal toxicity. Serum creatinine should be ≤1.5 mg/dL before beginning Proleukin. Monitor serum creatinine at baseline and daily throughout each course of therapy. Withhold Proleukin, or permanently discontinue, based on severity [see Dosage and Administration (2.4) ] . 5.5 Immune-mediated Adverse Reactions Exacerbation of pre-existing autoimmune disease or initial presentation of autoimmune and inflammatory disorders has been reported following treatment with Proleukin. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. These have included exacerbation of Crohn's disease, colitis, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, bullous pemphigoid, myocarditis, myositis, and neuritis including optic neuritis resulting in blindness [see Adverse Reactions (6.2) ] . Proleukin may increase the risk of allograft rejection in transplant patients [see Contraindications (4) ] . Hypothyroidism, sometimes preceded by hyperthyroidism, has been reported following Proleukin treatment. Evaluate thyroid function at baseline and periodically during treatment and initiate thyroid replacement therapy as clinically indicated. Hyperglycemia and/or diabetes mellitus has been reported during Proleukin therapy. Monitor patients for hyperglycemia and initiate treatment with insulin as clinically indicated. 5.6 Embryo-Fetal Toxicity Based on findings in an animal study and its mechanism of action, Proleukin may cause fetal harm or loss of pregnancy when administered to a pregnant woman.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling: Capillary Leak Syndrome [see Warnings and Precautions (5.1) ]. Neurotoxicity [see Warnings and Precautions (5.2) ]. Serious Infections Including Sepsis [see Warnings and Precautions (5.3) ]. Renal Toxicity [see Warnings and Precautions (5.4) ]. Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.5) ]. Serious Manifestations of Eosinophilia [see Warnings and Precautions (5.7) ]. Severe Hypersensitivity Reactions [see Warnings and Precautions (5.9) ]. Infusion-Related Reactions [see Warnings and Precautions (5.10) ] . Most common (≥ 30%) adverse reactions including laboratory abnormalities are hypotension, hyperbilirubinemia, dyspnea, rash, diarrhea, oliguria, chills, vomiting, thrombocytopenia, nausea, confusional state and increased creatinine. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Iovance Biotherapeutics Manufacturing LLC. at 1 844-845-IOVA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Proleukin was evaluated in a series of single and multicenter, controlled studies enrolling a total of 525 patients with metastatic renal cell carcinoma (mRCC studies) or metastatic melanoma (metastatic melanoma studies) [see Clinical Studies (14.1 , 14.2) ] . In patients who received Proleukin in these studies, fatal adverse reactions occurred in 4% (11/255) of the patients with metastatic RCC, and 2% (6/270) of the patients with metastatic melanoma. In these studies, >90% of patients had doses withheld for adverse reactions [see Dosage and Administration (2.4) ]. The most common (≥30%) adverse reactions were hypotension, hyperbilirubinemia, dyspnea, rash, diarrhea, oliguria, chills, vomiting, thrombocytopenia, nausea, confusional state, and increased creatinine. Table 4 summarizes adverse reactions that occurred in these studies. Table 4: Adverse Reactions (≥10% all grades or ≥1% Grade 4) in Patients with Metastatic Renal Cell Carcinoma or Metastatic Melanoma (n=525) receiving Proleukin Adverse Reaction Proleukin N = 525 All Grades (%) Grade 4 (%) General disorders Chills 52 0 Pyrexia 29 1 Edema peripheral 28 0 Malaise 27 0 Asthenia 23 0 Edema 15 0 Pain 12 0 Cardiac disorders Hypotension 71 3 Blood pressure fluctuation Not documented 1 Tachycardia 23 0 Dilated veins 13 0 Supraventricular tachycardia 12 1 Ventricular tachycardia <10 1 Cardiovascular disorder Cardiovascular disorder: Electrocardiogram abnormal, cardiac failure congestive. 11 0 Myocardial infarction <10 1 Arrhythmia 10 0 Cardiac arrest <10 1 Gastrointestinal disorders Diarrhea 67 2 Vomiting 50 0 Nausea 35 0 Stomatitis 22 <1 Decreased appetite 20 0 Abdominal pain 11 0 Abdominal distention 10 0 Blood and lymphatic system disorders Thrombocytopenia 37 1 Anemia 29 0 Leukopenia 16 0 Disseminated intravascular coagulation <10 1 Infections Infections 13 1 Sepsis <10 1 Hepatobiliary disorders Hyperbilirubinemia 40 2 Aspartate aminotransferase increased 23 1 Metabolic and nutritional disorders Weight increased 16 0 Acidosis 12 1 Hypomagnesemia 12 0 Hypocalcemia 11 <1 Blood alkaline phosphatase increased 10 0 Nervous system disorders Confusional state 34 1 Stupor <10 1 Coma <10 2 Psychotic disorder <10 1 Somnolence 22 0 Anxiety 12 0 Dizziness 11 0 Respiratory, thoracic, and mediastinal disorders Dyspnea 43 1 Lung disorder Lung disorder: Pulmonary congestion, rales, rhonchi. 24 0 Respiratory disorder Respiratory disorder: Acute respiratory distress syndrome, lung infiltration, lung disorder, respiratory failure, endotracheal intubation.
Drug interactions
Drug interaction studies with Proleukin have not been conducted. The drug interaction information described below have been observed post-marketing. See Full Prescribing Information for important drug interactions. ( 7 ) 7.1 Effect of Other Drugs on Proleukin Glucocorticoids Avoid concomitant use of glucocorticoids. Coadministration with glucocorticoids may reduce aldesleukin antitumor effectiveness. 7.2 Effect of Proleukin on Other Drugs Radiographic Iodinated Contrast Media Monitor for delayed adverse reactions in patients receiving iodinated contrast media following Proleukin. Administration of radiographic iodinated contrast media following administration of interleukin-2 resulted in acute, atypical adverse reactions that resemble the immediate side effects caused by Proleukin in some patients [see Warnings and Precautions (5.8) ] . Effect on Cytochrome P-450 Substrates For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentration changes of such CYP substrates when co-administered with Proleukin. Aldesleukin causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates.
Use in specific populations
Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in an animal study and its mechanism of action, Proleukin may cause fetal harm or loss of pregnancy when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. Data on the use of Proleukin in pregnant women are limited and insufficient to assess the drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes; however, development of capillary leak syndrome during pregnancy can lead to adverse fetal outcomes (see Clinical Considerations ) . Intravenous administration of aldesleukin to pregnant rats during the period of organogenesis resulted in embryo lethality at doses 27 times and maternal toxicities at doses 2.1 times the human exposure at the recommended clinical dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15–20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Capillary leak syndrome in women who are exposed to Proleukin during pregnancy may result in maternal hypotension and decreased placental perfusion. Severe or prolonged maternal hypotension and decreased placental perfusion can lead to intrauterine growth restriction, perinatal asphyxia, or fetal/neonatal demise. Monitor fetal and neonatal status in pregnant women who develop capillary leak syndrome associated with Proleukin. Data Animal Data Aldesleukin has been shown to have embryolethal effects in rats when given in doses at 27 to 36 times the human dose (scaled by body weight). Significant maternal toxicities were observed in pregnant rats administered aldesleukin by IV injection at doses 2.1 to 36 times higher than the human dose during critical period of organogenesis. 8.2 Lactation Risk Summary There are no data on the presence of aldesleukin in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Maternal cytokines are known to be present in human breast milk. Because of the potential for serious adverse reactions from Proleukin in a breastfed child, such as impaired immune function, advise women not to breastfeed during treatment. 8.3 Females and Males of Reproductive Potential Based on animal data and mechanism of action, Proleukin may cause embryo-fetal harm [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating Proleukin [see Use in Specific Populations (8.1) ]. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Proleukin. 8.4 Pediatric Use The safety and effectiveness of Proleukin have not been established in pediatric patients. 8.5 Geriatric Use Clinical studies of Proleukin did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in an animal study and its mechanism of action, Proleukin may cause fetal harm or loss of pregnancy when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. Data on the use of Proleukin in pregnant women are limited and insufficient to assess the drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes; however, development of capillary leak syndrome during pregnancy can lead to adverse fetal outcomes (see Clinical Considerations ) . Intravenous administration of aldesleukin to pregnant rats during the period of organogenesis resulted in embryo lethality at doses 27 times and maternal toxicities at doses 2.1 times the human exposure at the recommended clinical dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15–20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Capillary leak syndrome in women who are exposed to Proleukin during pregnancy may result in maternal hypotension and decreased placental perfusion. Severe or prolonged maternal hypotension and decreased placental perfusion can lead to intrauterine growth restriction, perinatal asphyxia, or fetal/neonatal demise. Monitor fetal and neonatal status in pregnant women who develop capillary leak syndrome associated with Proleukin. Data Animal Data Aldesleukin has been shown to have embryolethal effects in rats when given in doses at 27 to 36 times the human dose (scaled by body weight). Significant maternal toxicities were observed in pregnant rats administered aldesleukin by IV injection at doses 2.1 to 36 times higher than the human dose during critical period of organogenesis.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Proleukin have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use Clinical studies of Proleukin did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
Overdosage
Exceeding the recommended dose of Proleukin has been associated with a more rapid onset of severe or life-threatening toxicities. Treat toxicities supportively; life-threatening toxicities may be ameliorated by the intravenous administration of dexamethasone.
Description
Aldesleukin is a human interleukin-2 lymphocyte growth factor produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. It is a purified protein with a molecular weight of approximately 15,300 Da. This recombinant form differs from native interleukin-2 in the following ways: a) aldesleukin is not glycosylated; b) the molecule has no N-terminal alanine; c) the molecule has serine substituted for cysteine at amino acid position 125. Proleukin exists as biologically active, non-covalently bound microaggregates with an average size of 27 recombinant interleukin-2 molecules; the aggregation state of aldesleukin may differ compared to native interleukin-2. The manufacturing process for aldesleukin involves fermentation in a defined medium containing tetracycline hydrochloride. The presence of tetracycline hydrochloride is not detectable in the final product. Proleukin (aldesleukin) for injection is a sterile, preservative-free white to off-white, lyophilized powder, which has a cake-like appearance, supplied in single-dose vials for intravenous administration after reconstitution and dilution. When reconstituted with 1.2 mL Sterile Water for Injection, USP, each mL contains 18 million International Units (1.1 mg) aldesleukin, mannitol (50 mg), sodium dodecyl sulfate (0.19 mg), buffered with disodium hydrogen phosphate dihydrate (1.12 mg) and sodium dihydrogen phosphate dihydrate (0.19 mg) to a pH of 7.5 (range 7.2 to 7.8).
Mechanism of action
12.1 Mechanism of Action Aldesleukin is an interleukin-2 lymphocyte growth factor. The antitumor activity of aldesleukin has not been fully characterized. In vitro studies performed on human cell lines show enhancement of lymphocyte mitogenesis and cytotoxicity, induction of killer cell activity [lymphokine-activated killer (LAK) and natural killer (NK) cells] and interferon gamma production, and proliferation of human interleukin-2-dependent cell lines. Administration of aldesleukin in animals and humans produces multiple immunological effects in a dose-dependent manner. These effects include activation of cellular immunity 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.
How supplied
Proleukin ® (aldesleukin) for injection is supplied in single-dose vials. Each vial contains 22 million International Units (1.3 mg) of Proleukin. NDC 73776-022-01 Individually boxed single-dose vial Store unopened vials refrigerated at 2° to 8°C (36° to 46°F) in the original carton to protect from light. Do not use beyond the expiration date printed on the vial. NOTE: This product contains no preservative.
Storage
Store unopened vials refrigerated at 2° to 8°C (36° to 46°F) in the original carton to protect from light. Do not use beyond the expiration date printed on the vial. NOTE: This product contains no preservative.
Patient information
Inform patients or caregivers of the following risks of Proleukin: Capillary Leak Syndrome Advise patients about the risk of capillary leak syndrome and to inform their healthcare provider immediately if they develop new or worsening symptoms of hypotension, dyspnea, or edema [see Warnings and Precautions (5.1) ]. Neurotoxicity Advise the patient to inform their healthcare provider immediately if they develop mental status changes, speech difficulties, blindness, ataxia, hallucinations, agitation, or experienced a seizure [see Warnings and Precautions (5.2) ]. Serious Infections Including Sepsis Advise patients to inform their healthcare provider immediately if they develop signs of infection or sepsis including fever, chills, weakness, dyspnea [see Warnings and Precautions (5.3) ]. Immune-mediated Adverse Reactions Advise patients that Proleukin can cause immune-mediated adverse reactions and can exacerbate pre-existing autoimmune disease. These immune-mediated adverse reactions can occur in any organ system or tissue. Proleukin may also increase the risk of allograft rejection in transplant patients. Advise patients to contact their healthcare provider for any new or worsening signs or symptoms [see Warnings and Precautions (5.5) ] . Hypothyroidism, sometimes preceded by hyperthyroidism, has been reported following Proleukin treatment. Evaluate thyroid function at baseline and periodically during treatment and initiate thyroid replacement therapy as clinically indicated. Hyperglycemia and/or diabetes mellitus has been reported during Proleukin therapy. Monitor patients for hyperglycemia and initiate treatment with insulin as clinically indicated. Serious Manifestations of Eosinophilia Advise patients to inform their healthcare provider immediately if they develop serious symptoms of eosinophilia including new severe rash or dyspnea [see Warnings and Precautions (5.7) ]. Delayed Adverse Reactions to Iodinated Contrast Media Advise patients to inform their health care provider that they received Proleukin prior to undergoing imaging that requires iodinated contrast material [see Warnings and Precautions (5.8) ]. Embryo-Fetal Toxicity Advise females of reproductive potential to use effective contraception during treatment with Proleukin [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ] . Proleukin may cause fetal harm. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ] . Lactation Advise females not to breastfeed during treatment with Proleukin [see Use in Specific Populations (8.2) ] . Hypersensitivity Advise patients to inform their healthcare provider if they develop signs and symptoms of hypersensitivity reactions [see Warnings and Precautions (5.9) ].
Label text from the FDA structured product label by Iovance Biotherapeutics, Inc (revised Dec 20, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Aldesleukin in 1 product
Proleukin NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 73776-022 | Aldesleukin 1.1 mg/mL Injection, Powder, Lyophilized, For Solution | Iovance Biotherapeutics, Inc | BLA |
Frequently asked questions
What is Proleukin used for?
Proleukin is a lymphocyte growth factor indicated for: The treatment of adults with metastatic renal cell carcinoma. ( 1.1 ) The treatment of adults with metastatic melanoma. ( 1.2 ) 1.1 Metastatic Renal Cell Carcinoma Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma (RCC). 1.2 Metastatic Melanoma Proleukin is indicated for the treatment of adults with…
What are the side effects of Proleukin?
The following clinically significant adverse reactions are described elsewhere in the labeling: Capillary Leak Syndrome [see Warnings and Precautions (5.1) ]. Neurotoxicity [see Warnings and Precautions (5.2) ]. Serious Infections Including Sepsis [see Warnings and Precautions (5.3) ]. Renal Toxicity [see Warnings and Precautions (5.4) ]. Immune-Mediated Adverse Reactions [see Warnings and… See the full label for the complete list.
Who makes Proleukin?
Proleukin is listed by 1 labeler in the FDA NDC directory, including Iovance Biotherapeutics, Inc.