Proleukin

Metastatic Renal Cell Carcinoma

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

Metastatic Melanoma

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

 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 , Warnings and Precautions ].

Verify pregnancy status of females of reproductive potential prior to initiating Proleukin [see Warnings and Precautions , Use in Specific Populations ].

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 ].

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 ]. Discontinue Proleukin for unacceptable toxicity [see Dosage and Administration ].

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 ].

Separate each treatment course by a rest period of at least 7 weeks from the date of hospital discharge.

 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 ].

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 ].

Administer prophylactic medication for gastrointestinal irritation and bleeding during each Proleukin treatment course [see Adverse Reactions ].

Additional medications may be needed if patients experience hypotension, dyspnea, rigors, nausea, diarrhea, pruritis, or dermatitis [see Warnings and Precautions ].

 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.

 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:

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.

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 ]. 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

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.

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 ].

Pregnancy Testing

Verify pregnancy status of females of reproductive potential prior to initiating Proleukin [see Use in Specific Populations ].

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with Proleukin.

Pediatric Use

The safety and effectiveness of Proleukin have not been established in pediatric patients.

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.