PROLEUKIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROLEUKIN (PROLEUKIN).

How it works

Recombinant interleukin-2 (IL-2) that activates cellular immunity by promoting proliferation and differentiation of T cells, natural killer cells, and lymphokine-activated killer cells; stimulates cytokine release including TNF, IL-1, and IFN-gamma.

What the body does with it

Metabolism	Not extensively metabolized; primarily eliminated by renal catabolism (proximal tubular cells) and minimal hepatic metabolism.
Excretion	Renal (primarily via glomerular filtration and tubular reabsorption with subsequent metabolism; <1% excreted unchanged in urine); fecal/biliary elimination is negligible.
Half-life	Terminal elimination half-life is approximately 85 minutes (range 25-195 minutes) after intravenous infusion; clinical context: short half-life necessitates continuous infusion for sustained immunomodulatory effect.
Protein binding	~30% bound to serum proteins (primarily albumin).
Volume of Distribution	Vd approximately 0.15-0.25 L/kg; indicates distribution primarily within the vascular space and interstitial fluid, with limited extravascular penetration.
Bioavailability	Intravenous: 100% (only route of administration due to degradation in gastrointestinal tract and poor absorption via other routes).
Onset of Action	Intravenous: Clinical effects (lymphocyte activation, cytokine release) begin within 15-30 minutes after infusion initiation.
Duration of Action	Duration of immunologic effects (e.g., lymphocytosis, cytokine elevation) persists for 4-8 hours after infusion; clinical antitumor response may require multiple cycles over weeks.

Classification & Brands

Dosing & administration

600,000 IU/kg (0.037 mg/kg) intravenously every 8 hours for 14 doses, repeated after 9 days for a maximum of 28 doses per course.

Dosage form	VIAL
Renal impairment	No specific dose adjustment provided; use with caution in renal impairment. Discontinue if serum creatinine >4.5 mg/dL or if oliguria persists despite fluid resuscitation.
Liver impairment	No specific dose adjustment provided; use with caution in hepatic impairment. Discontinue if bilirubin >4 mg/dL or if signs of hepatic failure occur.
Pediatric use	Safety and efficacy not established in children under 18 years. Limited data available; use not recommended.
Geriatric use	No specific dose adjustment; clinical studies did not include sufficient numbers of patients aged 65 and over to determine differences in response. Use with caution due to increased risk of renal, hepatic, and cardiac toxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROLEUKIN (PROLEUKIN).

Breastfeeding	No human data; aldesleukin likely present in breast milk due to molecular weight (~15 kDa). M/P ratio unknown. Risk of immune suppression and adverse effects in infant. Discontinue breastfeeding or drug.
Teratogenic Risk	Pregnancy Category C. First trimester: Potential for embryolethality and teratogenicity based on animal studies; no adequate human data. Second and third trimesters: Risk of fetal harm due to cytokine storm, capillary leak syndrome, and maternal hypotension compromising placental perfusion.

Warnings & precautions

■ FDA Black Box Warning

PROLEUKIN is associated with severe, life-threatening adverse events including capillary leak syndrome (CLS) with hypotension, pulmonary edema, renal impairment, and arrhythmias. Treatment should be restricted to patients with normal cardiac and pulmonary function, and only administered in a hospital setting with intensive care unit support.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of hypersensitivity to interleukin-2 or any component of PROLEUKIN","Abnormal cardiac or pulmonary function tests (stress test, PFTs)","Organ allografts (risk of graft rejection)","Concurrent use of immunosuppressive agents"]

Clinical Precautions

Precautions

["Capillary leak syndrome (hypotension, pulmonary edema, renal failure)","Cardiac toxicity (arrhythmias, myocardial ischemia)","Neurologic toxicity (disorientation, seizures)","Pulmonary toxicity (respiratory failure)","Renal toxicity (oliguria, increased serum creatinine)","Infections (sepsis, catheter-related infections)","Hypersensitivity reactions"]

Clinical Tips & Counseling

Drug interactions

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PROLEUKIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROLEUKIN (PROLEUKIN).

How it works

What the body does with it

Metabolism	Not extensively metabolized; primarily eliminated by renal catabolism (proximal tubular cells) and minimal hepatic metabolism.
Excretion	Renal (primarily via glomerular filtration and tubular reabsorption with subsequent metabolism; <1% excreted unchanged in urine); fecal/biliary elimination is negligible.
Half-life	Terminal elimination half-life is approximately 85 minutes (range 25-195 minutes) after intravenous infusion; clinical context: short half-life necessitates continuous infusion for sustained immunomodulatory effect.
Protein binding	~30% bound to serum proteins (primarily albumin).
Volume of Distribution	Vd approximately 0.15-0.25 L/kg; indicates distribution primarily within the vascular space and interstitial fluid, with limited extravascular penetration.
Bioavailability	Intravenous: 100% (only route of administration due to degradation in gastrointestinal tract and poor absorption via other routes).
Onset of Action	Intravenous: Clinical effects (lymphocyte activation, cytokine release) begin within 15-30 minutes after infusion initiation.
Duration of Action	Duration of immunologic effects (e.g., lymphocytosis, cytokine elevation) persists for 4-8 hours after infusion; clinical antitumor response may require multiple cycles over weeks.

Classification & Brands

Dosing & administration

600,000 IU/kg (0.037 mg/kg) intravenously every 8 hours for 14 doses, repeated after 9 days for a maximum of 28 doses per course.

Dosage form	VIAL
Renal impairment	No specific dose adjustment provided; use with caution in renal impairment. Discontinue if serum creatinine >4.5 mg/dL or if oliguria persists despite fluid resuscitation.
Liver impairment	No specific dose adjustment provided; use with caution in hepatic impairment. Discontinue if bilirubin >4 mg/dL or if signs of hepatic failure occur.
Pediatric use	Safety and efficacy not established in children under 18 years. Limited data available; use not recommended.
Geriatric use	No specific dose adjustment; clinical studies did not include sufficient numbers of patients aged 65 and over to determine differences in response. Use with caution due to increased risk of renal, hepatic, and cardiac toxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROLEUKIN (PROLEUKIN).

Breastfeeding	No human data; aldesleukin likely present in breast milk due to molecular weight (~15 kDa). M/P ratio unknown. Risk of immune suppression and adverse effects in infant. Discontinue breastfeeding or drug.
Teratogenic Risk	Pregnancy Category C. First trimester: Potential for embryolethality and teratogenicity based on animal studies; no adequate human data. Second and third trimesters: Risk of fetal harm due to cytokine storm, capillary leak syndrome, and maternal hypotension compromising placental perfusion.