MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Showing posts with label Aldesleukin. Show all posts
Showing posts with label Aldesleukin. Show all posts
Monday, May 24, 2010
Aldesleukin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Sunday, March 2, 2008
Aldesleukin
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma: I.V.: Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course. In combination with cytotoxic agents: 24 million int. units/m2 days 12-16 and 19-23 SubQ: Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks In combination with interferon: 5 million int. units/m2 3 times/week 1.8 million int. units/m2 twice daily 5 days/week for 6 weeks Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes; may be administered by SubQ injection
Management of symptoms related to vascular leak syndrome: If actual body weight increases >10% above baseline, or rales or rhonchi are audible: Administer furosemide at dosage determined by patient response Administer dopamine hydrochloride 2-4 mcg/kg/minute to maintain renal blood flow and urine output If patient has dyspnea at rest: Administer supplemental oxygen by face mask If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, melanoma
USE - UNLABELED / INVESTIGATIONAL — Investigational: Multiple myeloma, HIV infection, and AIDS; may be used in conjunction with lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocyte (TIL) cells, interleukin-1, and interferons; colorectal cancer; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Sensory dysfunction, sinus tachycardia, arrhythmia, pulmonary congestion; hypotension (dose-limiting toxicity) which may require vasopressor support and hemodynamic changes resembling those seen in septic shock can be seen within 2 hours of administration; chest pain, acute MI, SVT with hypotension has been reported, edema Central nervous system: Dizziness, pain, fever, chills, cognitive changes, fatigue, malaise, disorientation, somnolence, paranoid delusion, and other behavioral changes; reversible and dose related; however, may continue to worsen for several days even after the infusion is stopped Dermatologic: Pruritus, erythema, rash, dry skin, exfoliative dermatitis, macular erythema Gastrointestinal: Nausea, vomiting, weight gain, diarrhea, stomatitis, anorexia, GI bleeding Hematologic: Anemia, thrombocytopenia, leukopenia, eosinophilia, coagulation disorders Hepatic: Transaminases increased, alkaline phosphatase increased, jaundice Neuromuscular & skeletal: Weakness, rigors which can be decreased or ameliorated with acetaminophen or a nonsteroidal agent and meperidine Renal: Oliguria, anuria, proteinuria; renal failure (dose-limiting toxicity) manifested as oliguria noted within 24-48 hours of initiation of therapy; marked fluid retention, azotemia, and increased serum creatinine seen, which may return to baseline within 7 days of discontinuation of therapy; hypophosphatemia Respiratory: Dyspnea, pulmonary edema
1% to 10%: Cardiovascular: Increase in vascular permeability: Capillary-leak syndrome manifested by severe peripheral edema, ascites, pulmonary infiltration, and pleural effusion; occurs in 2% to 4% of patients and is resolved after therapy ends
<1% (Limited to important or life-threatening): Alopecia, coma, CHF, pancreatitis, polyuria, seizure
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation 72 hours, pericardial tamponade, renal dialysis for 72 hours, coma or toxic psychosis lasting 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS Box warnings: Capillary leak syndrome (CLS): See "Concerns related to adverse effects" below. Experienced physician: See "Other warnings/precautions" below. Infection: See "Concerns related to adverse effects" below. Lethargy/somnolence: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS Beta-blockers and other antihypertensives may potentiate the hypotension seen with aldesleukin.
Corticosteroids: Have been shown to decrease toxicity of aldesleukin, but may decrease the efficacy of the lymphokine.
Increased toxicity: Concomitant administration of drugs possessing nephrotoxic (eg, aminoglycosides, indomethacin), myelotoxic (eg, cytotoxic chemotherapy), cardiotoxic (eg, doxorubicin), or hepatotoxic effects with aldesleukin may increase toxicity in these organ systems.
Iodinated contrast media: Acute reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria have occurred within hours of contrast infusion; this reaction may occur within 4 weeks or up to several months after aldesleukin administration.
Psychotropic agents: Aldesleukin may affect central nervous function; therefore, interactions could occur following concomitant administration of psychotropic drugs (eg, narcotics, analgesics, antiemetics, sedatives, tranquilizers).
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)Injection (reconstituted) (Proleukin) 22000000 unit (1): $855.71
MONITORING PARAMETERS The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration: Standard hematologic tests including CBC, differential, and platelet counts; blood chemistries including electrolytes, renal and hepatic function tests Chest x-rays Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked. During treatment, pulmonary function should be monitored on a regular basis.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Side effects following the use of aldesleukin are dose related. Administration of more than the recommended dose has been associated with a more rapid onset of expected dose-limiting toxicities. Adverse reactions generally will reverse when the drug is stopped, particularly because of its short serum half-life. Provide supportive treatment of any continuing symptoms. Life-threatening toxicities have been ameliorated by the I.V. administration of dexamethasone, which may decrease the therapeutic effect of aldesleukin.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CL); Proleukin (AR, AT, BE, BR, CA, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IT, KR, MX, NL, NZ, PE, PL, SG, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Bioavailability: I.M.: 37%
Half-life elimination: Initial: 6-13 minutes; Terminal: 80-120 minutes
PHARMACOLOGIC CATEGORY Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma: I.V.: Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course. In combination with cytotoxic agents: 24 million int. units/m2 days 12-16 and 19-23 SubQ: Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks In combination with interferon: 5 million int. units/m2 3 times/week 1.8 million int. units/m2 twice daily 5 days/week for 6 weeks Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes; may be administered by SubQ injection
Management of symptoms related to vascular leak syndrome: If actual body weight increases >10% above baseline, or rales or rhonchi are audible: Administer furosemide at dosage determined by patient response Administer dopamine hydrochloride 2-4 mcg/kg/minute to maintain renal blood flow and urine output If patient has dyspnea at rest: Administer supplemental oxygen by face mask If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, melanoma
USE - UNLABELED / INVESTIGATIONAL — Investigational: Multiple myeloma, HIV infection, and AIDS; may be used in conjunction with lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocyte (TIL) cells, interleukin-1, and interferons; colorectal cancer; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Sensory dysfunction, sinus tachycardia, arrhythmia, pulmonary congestion; hypotension (dose-limiting toxicity) which may require vasopressor support and hemodynamic changes resembling those seen in septic shock can be seen within 2 hours of administration; chest pain, acute MI, SVT with hypotension has been reported, edema Central nervous system: Dizziness, pain, fever, chills, cognitive changes, fatigue, malaise, disorientation, somnolence, paranoid delusion, and other behavioral changes; reversible and dose related; however, may continue to worsen for several days even after the infusion is stopped Dermatologic: Pruritus, erythema, rash, dry skin, exfoliative dermatitis, macular erythema Gastrointestinal: Nausea, vomiting, weight gain, diarrhea, stomatitis, anorexia, GI bleeding Hematologic: Anemia, thrombocytopenia, leukopenia, eosinophilia, coagulation disorders Hepatic: Transaminases increased, alkaline phosphatase increased, jaundice Neuromuscular & skeletal: Weakness, rigors which can be decreased or ameliorated with acetaminophen or a nonsteroidal agent and meperidine Renal: Oliguria, anuria, proteinuria; renal failure (dose-limiting toxicity) manifested as oliguria noted within 24-48 hours of initiation of therapy; marked fluid retention, azotemia, and increased serum creatinine seen, which may return to baseline within 7 days of discontinuation of therapy; hypophosphatemia Respiratory: Dyspnea, pulmonary edema
1% to 10%: Cardiovascular: Increase in vascular permeability: Capillary-leak syndrome manifested by severe peripheral edema, ascites, pulmonary infiltration, and pleural effusion; occurs in 2% to 4% of patients and is resolved after therapy ends
<1% (Limited to important or life-threatening): Alopecia, coma, CHF, pancreatitis, polyuria, seizure
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation 72 hours, pericardial tamponade, renal dialysis for 72 hours, coma or toxic psychosis lasting 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS Box warnings: Capillary leak syndrome (CLS): See "Concerns related to adverse effects" below. Experienced physician: See "Other warnings/precautions" below. Infection: See "Concerns related to adverse effects" below. Lethargy/somnolence: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS Beta-blockers and other antihypertensives may potentiate the hypotension seen with aldesleukin.
Corticosteroids: Have been shown to decrease toxicity of aldesleukin, but may decrease the efficacy of the lymphokine.
Increased toxicity: Concomitant administration of drugs possessing nephrotoxic (eg, aminoglycosides, indomethacin), myelotoxic (eg, cytotoxic chemotherapy), cardiotoxic (eg, doxorubicin), or hepatotoxic effects with aldesleukin may increase toxicity in these organ systems.
Iodinated contrast media: Acute reactions including fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria have occurred within hours of contrast infusion; this reaction may occur within 4 weeks or up to several months after aldesleukin administration.
Psychotropic agents: Aldesleukin may affect central nervous function; therefore, interactions could occur following concomitant administration of psychotropic drugs (eg, narcotics, analgesics, antiemetics, sedatives, tranquilizers).
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)Injection (reconstituted) (Proleukin) 22000000 unit (1): $855.71
MONITORING PARAMETERS The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration: Standard hematologic tests including CBC, differential, and platelet counts; blood chemistries including electrolytes, renal and hepatic function tests Chest x-rays Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked. During treatment, pulmonary function should be monitored on a regular basis.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Side effects following the use of aldesleukin are dose related. Administration of more than the recommended dose has been associated with a more rapid onset of expected dose-limiting toxicities. Adverse reactions generally will reverse when the drug is stopped, particularly because of its short serum half-life. Provide supportive treatment of any continuing symptoms. Life-threatening toxicities have been ameliorated by the I.V. administration of dexamethasone, which may decrease the therapeutic effect of aldesleukin.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CL); Proleukin (AR, AT, BE, BR, CA, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IT, KR, MX, NL, NZ, PE, PL, SG, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Bioavailability: I.M.: 37%
Half-life elimination: Initial: 6-13 minutes; Terminal: 80-120 minutes
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