Proleukin

• Capillary leak syndrome (CLS), including life threatening or fatal reactions, has occurred in patients treated with Proleukin. Do not administer Proleukin to patients with significant cardiac, pulmonary, renal, and hepatic impairment. Administer Proleukin in a hospital setting with an intensive care facility. Withhold or discontinue Proleukin as recommended
  
  

  [see
  
  

  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. Initiate a new course of treatment no sooner than 7 weeks after signs of hepatic toxicity have resolved and hospital discharge
  	Hepatic failure	Permanently discontinue
  Dermatologic [see Warnings and Precautions (5.5, 5.7)]	Bullous dermatitis or marked worsening of pre-existing skin condition	Withhold until all signs of bullous dermatitis have resolved
  Infectious [see Warnings and Precautions (5.3)]	Sepsis syndrome, patient is clinically unstable	Withhold until sepsis syndrome has resolved, patient is clinically stable, infection is under treatment
  Renal [see Warnings and Precautions (5.1, 5.4)]	Serum creatinine >4.5 mg/dL or a serum creatinine of ≥4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia	Withhold until serum creatinine levels return to normal (<1.5 mg/dL) or baseline and fluid and electrolyte status are stable
  	Persistent oliguria, urine output of <10 mL/hr for 16-24 hours with rising SCr	Withhold until urine output >10 mL/hour with a decrease of serum creatinine >1.5 mg/dL or normalization of serum creatinine
  	Renal failure requiring dialysis >72 hours	Permanently discontinue

  ,
  
  

  4 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.
  • Organ allografts.
  • Significant organ impairment.

  ,
  
  

  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)]

  .

  ]
  
  

  .
  
  
• Neurologic toxicities, which may be life-threatening or result in coma or permanent neurological deficits, have occurred in patients treated with Proleukin. Withhold or discontinue Proleukin as recommended
  
  

  [see
  
  

  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. Initiate a new course of treatment no sooner than 7 weeks after signs of hepatic toxicity have resolved and hospital discharge
  	Hepatic failure	Permanently discontinue
  Dermatologic [see Warnings and Precautions (5.5, 5.7)]	Bullous dermatitis or marked worsening of pre-existing skin condition	Withhold until all signs of bullous dermatitis have resolved
  Infectious [see Warnings and Precautions (5.3)]	Sepsis syndrome, patient is clinically unstable	Withhold until sepsis syndrome has resolved, patient is clinically stable, infection is under treatment
  Renal [see Warnings and Precautions (5.1, 5.4)]	Serum creatinine >4.5 mg/dL or a serum creatinine of ≥4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia	Withhold until serum creatinine levels return to normal (<1.5 mg/dL) or baseline and fluid and electrolyte status are stable
  	Persistent oliguria, urine output of <10 mL/hr for 16-24 hours with rising SCr	Withhold until urine output >10 mL/hour with a decrease of serum creatinine >1.5 mg/dL or normalization of serum creatinine
  	Renal failure requiring dialysis >72 hours	Permanently discontinue

  ,
  
  

  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.

  ]
  
  

  .
  
  
• Serious Infections including sepsis and bacterial endocarditis have occurred in patients treated with Proleukin. Treat pre-existing bacterial infections prior to initiation of Proleukin therapy and withhold Proleukin as recommended
  
  

  [see
  
  

  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. Initiate a new course of treatment no sooner than 7 weeks after signs of hepatic toxicity have resolved and hospital discharge
  	Hepatic failure	Permanently discontinue
  Dermatologic [see Warnings and Precautions (5.5, 5.7)]	Bullous dermatitis or marked worsening of pre-existing skin condition	Withhold until all signs of bullous dermatitis have resolved
  Infectious [see Warnings and Precautions (5.3)]	Sepsis syndrome, patient is clinically unstable	Withhold until sepsis syndrome has resolved, patient is clinically stable, infection is under treatment
  Renal [see Warnings and Precautions (5.1, 5.4)]	Serum creatinine >4.5 mg/dL or a serum creatinine of ≥4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia	Withhold until serum creatinine levels return to normal (<1.5 mg/dL) or baseline and fluid and electrolyte status are stable
  	Persistent oliguria, urine output of <10 mL/hr for 16-24 hours with rising SCr	Withhold until urine output >10 mL/hour with a decrease of serum creatinine >1.5 mg/dL or normalization of serum creatinine
  	Renal failure requiring dialysis >72 hours	Permanently discontinue

  ,
  
  

  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)].

  ]
  
  

  .
  
  

Proleukin is a lymphocyte growth factor indicated for:

• The treatment of adults with metastatic renal cell carcinoma. (
  
  
  1.1 Metastatic Renal Cell Carcinoma

  Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma (RCC).
  )
  
• The treatment of adults with metastatic melanoma. (
  
  
  1.2 Metastatic Melanoma

  Proleukin is indicated for the treatment of adults with metastatic melanoma.
  )
  

Administer Proleukin in an inpatient hospital setting with an intensive care facility.

• Evaluate cardiovascular, pulmonary, neurologic and renal function before beginning Proleukin. (
  
  
  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)].
  )
  
• See Full Prescribing Information for Premedication and Supportive medications. (
  
  
  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)].
  )
  
• 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 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 dosesA 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.
  )
  
• 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 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 dosesA 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.
  )
  
• Dose modification for toxicity should be accomplished by withholding or interrupting a dose. (
  
  
  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. Initiate a new course of treatment no sooner than 7 weeks after signs of hepatic toxicity have resolved and hospital discharge
  	Hepatic failure	Permanently discontinue
  Dermatologic [see Warnings and Precautions (5.5, 5.7)]	Bullous dermatitis or marked worsening of pre-existing skin condition	Withhold until all signs of bullous dermatitis have resolved
  Infectious [see Warnings and Precautions (5.3)]	Sepsis syndrome, patient is clinically unstable	Withhold until sepsis syndrome has resolved, patient is clinically stable, infection is under treatment
  Renal [see Warnings and Precautions (5.1, 5.4)]	Serum creatinine >4.5 mg/dL or a serum creatinine of ≥4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia	Withhold until serum creatinine levels return to normal (<1.5 mg/dL) or baseline and fluid and electrolyte status are stable
  	Persistent oliguria, urine output of <10 mL/hr for 16-24 hours with rising SCr	Withhold until urine output >10 mL/hour with a decrease of serum creatinine >1.5 mg/dL or normalization of serum creatinine
  	Renal failure requiring dialysis >72 hours	Permanently discontinue
  )
  
• Follow reconstitution and dilution procedures. (
  
  
  2.5 Preparation and Administration

  Preparation

  Reconstitute Proleukin using Sterile Water for Injection, USP. Do not reconstitute or dilute Proleukin with Bacteriostatic Water for Injection, or 0.9% Sodium Chloride Injection.

  • Add 1.2 mL of Sterile Water for Injection, USP, by injecting the water along the walls of the vial and not directly on the lyophilized powder. The resulting concentration is 18 million IU (1.1 mg)/mL of Proleukin.
  • The prepared solution is a clear, colorless to slightly yellow liquid.
  • Slowly swirl the vial; do not shake.
  • Withdraw the required dose of Proleukin and discard the vial with any unused portion.
  • Use polyvinyl chloride bags for dilution of Proleukin and dilute using 5% Dextrose Injection to a concentration between 0.03 mg/mL and 0.07 mg/mL based on the required dose as follows:

  Table 3: Recommended Proleukin Dilution

  Dose	5% Dextrose Volume
  ≤25.4 million IU (≤1.5 mg)	25 mL
  >25.4 million IU-60 million IU (>1.5 mg-3.5 mg)	50 mL
  >60 million IU (>3.5 mg)	100 mL

  Storage of Diluted Proleukin Infusion Solution

  • Store under refrigeration at 2° to 8°C (36° to 46°F) for no more than 48 hours from the time of preparation to the end of the infusion.
  • Protect from light.
  • Do not freeze.
  • Allow the diluted solution to come to room temperature prior to administration.

  Administration

  • Do not use in-line filters when administering Proleukin.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  • Do not co-administer Proleukin with other drugs through the same intravenous line.
  • Administer by intravenous infusion over 15 minutes.
  )
  

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.

• Pregnancy: May cause fetal harm. (
  
  
  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.
  )
  
• Lactation: Advise not to breastfeed. (
  
  
  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.
  )