PROLEUKIN Dailymed

1 Indications And Usage

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)

1.1Metastatic Renal Cell Carcinoma

Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma (RCC).

1.2Metastatic Melanoma

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

2 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)

2.1Recommended 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)].

2.2Recommended Dosage

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

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. 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

2.5Preparation 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.

• 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)