Version May 2024
Capillary leak syndrome, including life-threatening or fatal reactions, has occurred in patients treated with aldesleukin. Do not administer aldesleukin to patients with significant cardiac, pulmonary, renal, and hepatic impairment. Administer aldesleukin in a hospital setting with an intensive care facility. Withhold or discontinue aldesleukin as recommended.
Neurologic toxicity, which may be life-threatening or result in coma or permanent neurological deficits, has occurred in patients treated with aldesleukin. Withhold or discontinue aldesleukin as recommended.
Serious infections including sepsis and bacterial endocarditis have occurred in patients treated with aldesleukin. Treat preexisting bacterial infections prior to initiation of aldesleukin therapy and withhold aldesleukin as recommended.
Do not administer aldesleukin in patients with significant cardiac, pulmonary, kidney, or hepatic impairment. Evaluate and treat CNS metastases prior to aldesleukin treatment initiation; avoid use in patients with seizure disorder or abnormal CNS imaging. Treat preexisting bacterial infections prior to aldesleukin treatment initiation. Serum creatinine should be <1.5 mg/dL prior to aldesleukin treatment initiation.
Premedication: Premedicate patients with an antipyretic immediately prior to treatment initiation and continue as needed to reduce fever. Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Prophylaxis: Consider antibiotic prophylaxis (per institutional guidance) prior to and during treatment with aldesleukin in patients with indwelling central lines. Administer GI prophylaxis (for GI irritation/bleeding) during treatment with aldesleukin.
Melanoma, metastatic: IV: 600,000 units/kg every 8 hours for a maximum of 14 doses (days 1 to 5); after 9 days off have elapsed (days 6 to 14), repeat with a second cycle (on days 15 to 19) for a maximum of 28 doses per course (Ref); evaluate for response ~4 weeks after completion of course and again immediately prior to next treatment cycle; additional courses may be administered at least 7 weeks after hospital discharge date, if treatment response observed without adverse events leading to treatment discontinuation.
Off-label dosing: 720,000 units/kg every 8 hours for 14 doses; repeat cycle after a 6- to 9-day rest period. Additional courses of treatment were administered if tumor regression occurred or for stable disease (up to maximum of 5 treatment courses); each course of therapy was typically separated by a 6- to 12-week interval (Ref) or 720,000 units/kg every 8 hours for 12 to 15 doses; repeat with a second cycle ~14 days after the first dose of the initial cycle (Ref).
Renal cell carcinoma, metastatic: Note: May be an option in patients with progression following treatment with PD-1/PD-L1 inhibitors (Ref).
IV: 600,000 units/kg every 8 hours for a maximum of 14 doses (days 1 to 5); after 9 days off have elapsed (days 6 to 14), repeat with a second cycle (on days 15 to 19) for a maximum of 28 doses per course (Ref); evaluate for response ~4 weeks after completion of course and again immediately prior to next treatment cycle; additional courses may be administered at least 7 weeks after hospital discharge date, if treatment response observed without adverse events leading to treatment discontinuation.
Off-label dosing: IV: 720,000 units/kg every 8 hours for up to 12 doses; then after 10 to 15 days have elapsed, repeat with a second cycle for a total of 24 doses per course; may repeat course if tumor regression observed or stable disease (and if no contraindications) at least 2 months after hospital discharge date (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation:
Serum creatinine ≤1.5 mg/dL: There are no dosage adjustments provided in the manufacturer's labeling.
Serum creatinine >1.5 mg/dL: Do not initiate aldesleukin; treatment is contraindicated in significant kidney impairment.
Acute kidney toxicity during treatment:
Serum creatinine >4.5 mg/dL (or ≥4 mg/dL with severe volume overload, acidosis, or hyperkalemia): Withhold aldesleukin; may resume when serum creatinine <1.5 mg/dL or baseline and with stable fluid and electrolyte status.
Persistent oliguria or urine output <10 mL/hour for 16 to 24 hours with rising serum creatinine: Withhold aldesleukin; may resume when urine output is >10 mL/hour with serum creatinine decrease of >1.5 mg/dL or normalization.
Kidney failure requiring hemodialysis for >72 hours: Permanently discontinue aldesleukin.
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; however, aldesleukin is contraindicated in significant hepatic impairment.
Acute hepatotoxicity during treatment:
Liver pain or ≥ grade 3 AST or ALT elevation: Withhold aldesleukin and discontinue balance of cycle; may initiate a new course of treatment (if indicated) no sooner than 7 weeks following resolution of signs of hepatic toxicity and hospital discharge.
Hepatic failure: Permanently discontinue aldesleukin.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Withhold or interrupt a dose, or permanently discontinue aldesleukin for toxicity; do not reduce the dose.
|
Adverse reaction |
Severity |
Aldesleukin dosage modification |
|---|---|---|
|
a CLS = capillary leak syndrome; FIT = fecal immunochemical test; FOBT = fecal occult blood test. | ||
|
Cardiovascular toxicity |
Atrial fibrillation, supraventricular tachycardia, bradycardia (requiring treatment, or is recurrent or persistent) |
Withhold aldesleukin until patient is asymptomatic with full recovery to normal sinus rhythm. Initiate standard management for CLSa, including intensive care, as necessary. |
|
Decrease in systolic BP to <90 mm Hg (with increasing requirements for pressors) |
Withhold aldesleukin; may resume when systolic BP ≥90 mm Hg and stable or pressor requirements improve. | |
|
Sustained ventricular tachycardia (≥5 beats), cardiac rhythm disturbances not controlled or unresponsive to treatment, ECG changes consistent with myocardial infarction, ischemia, angina/chest pain, or cardiac tamponade |
Permanently discontinue aldesleukin. Initiate standard management for CLS, including intensive care, as necessary. | |
|
CNS toxicity |
Mental status changes, including moderate confusion, moderate to severe lethargy or somnolence, or agitation |
Withhold aldesleukin until complete resolution. Initiate standard management for CLS, including intensive care, as necessary. |
|
Coma or toxic psychosis lasting >48 hours, seizures (repetitive or difficult to control) |
Permanently discontinue aldesleukin. Initiate standard management for CLS, including intensive care, as necessary. | |
|
Dermatologic toxicity |
Bullous dermatitis or marked worsening of preexisting skin condition |
Withhold aldesleukin until resolution of all signs of bullous dermatitis. |
|
GI toxicity |
FITa or FOBTa positive |
Withhold aldesleukin until FIT or FOBT negative. |
|
Bowel ischemia/perforation or GI bleeding (requiring surgery) |
Permanently discontinue aldesleukin. | |
|
Hyperglycemia and/or diabetes mellitus |
Any (clinically significant) |
Initiate treatment with insulin as clinically indicated. |
|
Hypersensitivity reaction |
Severe |
Permanently discontinue aldesleukin. |
|
Hypothyroidism |
Any (clinically significant) |
Initiate thyroid replacement therapy as clinically indicated. |
|
Infection |
Sepsis, hemodynamic instability |
Withhold aldesleukin until resolution of sepsis syndrome, infection is being treated, and patient is clinically stable. |
|
Infusion-related reaction |
Any (clinically significant) |
Continue antipyretic therapy during treatment as needed for fever. |
|
Respiratory toxicity |
Oxygen saturation <90% |
Withhold aldesleukin until oxygen saturation is >90%. Initiate standard management for CLS, including intensive care, as necessary. |
|
Intubation for >72 hours |
Permanently discontinue aldesleukin. Initiate standard management for CLS, including intensive care, as necessary. | |
Refer to adult dosing.
(For additional information see "Aldesleukin: Pediatric drug information")
Dosage guidance:
Clinical considerations: Dosing and frequency may vary by indication, protocol, and/or treatment phase and hematologic response; refer to specific protocols. Consider premedication with an antipyretic to reduce fever, an H2 antagonist for prophylaxis of gastrointestinal irritation/bleeding, antiemetics, and antidiarrheals; continue for 12 hours after the last aldesleukin dose. Antibiotic prophylaxis is recommended to reduce the incidence of infection. Recommendations for antiemetics use may vary: Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref); however, aldesleukin is not included in the most updated pediatric classification of acute emetogenicity clinical practice guideline (Ref).
Neuroblastoma: Limited data available: Note: Although aldesleukin was used in earlier protocols, it is no longer considered as standard of care in combination with isotretinoin, dinutuximab, and sargramostim due to increased adverse effects and no additional efficacy benefit (Ref).
Children and Adolescents: IV: 3 million units/m2/day continuous infusion over 24 hours for 4 consecutive days during week 1 and 4.5 million units/m2/day continuous infusion over 24 hours for 4 consecutive days during week 2 of cycles 2 and 4 (regimen also includes isotretinoin, dinutuximab [an anti-GD2 antibody], and sargramostim) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: There are no pediatric-specific recommendations; the presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.
Adult:
Withhold or interrupt a dose for toxicity; do not reduce the dose.
Cardiovascular toxicity:
Atrial fibrillation, supraventricular tachycardia, or bradycardia that is persistent, recurrent, or requires treatment: Withhold dose; may resume when asymptomatic with full recovery to normal sinus rhythm.
Systolic BP <90 mm Hg (with increasing pressor requirements): Withhold dose; may resume treatment when systolic BP ≥90 mm Hg and stable or pressor requirements improve.
Any ECG change consistent with myocardial infarction (MI), ischemia or myocarditis (with or without chest pain), or suspected cardiac ischemia: Withhold dose; may resume when asymptomatic, MI/myocarditis have been ruled out, suspicion of angina is low, or there is no evidence of ventricular hypokinesia.
CNS toxicity: Mental status change, including moderate confusion or agitation. Withhold dose; may resume when resolved completely.
Dermatologic toxicity: Bullous dermatitis or marked worsening of preexisting skin condition: Withhold dose; may treat with antihistamines or topical products (do not use topical steroids); may resume with resolution of all signs of bullous dermatitis.
Gastrointestinal: Stool guaiac repeatedly >3 to 4+: Withhold dose; may resume with negative stool guaiac.
Infection: Sepsis syndrome, clinically unstable: Withhold dose; may resume when sepsis syndrome has resolved, patient is clinically stable, and infection is under treatment.
Respiratory toxicity: Oxygen saturation <90%: Withhold dose; may resume when >90%.
Retreatment with aldesleukin is contraindicated with the following toxicities: Sustained ventricular tachycardia (≥5 beats), uncontrolled or unresponsive cardiac arrhythmias, chest pain with ECG changes consistent with angina or MI, cardiac tamponade, intubation >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or refractory seizures, bowel ischemia/perforation, or GI bleeding requiring surgery.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Cardiac disorder (11%; including ECG abnormality, heart failure), edema (15%), hypotension (71%), peripheral edema (28%), supraventricular tachycardia (12%), tachycardia (23%), vasodilation (13%)
Dermatologic: Exfoliative dermatitis (18%), pruritus (24%), skin rash (42%)
Endocrine & metabolic: Acidosis (12%), hypocalcemia (11%), hypomagnesemia (12%), weight gain (16%)
Gastrointestinal: Abdominal pain (11%), decreased appetite (20%), diarrhea (67%; grade 4: 2%), nausea (35%), stomatitis (22%; grade 4: <1%), vomiting (50%)
Genitourinary: Oliguria (63%)
Hematologic & oncologic: Anemia (29%), leukopenia (16%), thrombocytopenia (37%; grade 4: 1%)
Hepatic: Hyperbilirubinemia (40%), increased serum aspartate aminotransferase (23%)
Immunologic: Antibody development (66% to 74%; neutralizing: <1%)
Infection: Infection (13%, including sepsis [<10%], serious infection)
Nervous system: Anxiety (12%), asthenia (23%), chills (52%), confusion (34%), dizziness (11%), drowsiness (22%), malaise (27%), pain (12%)
Renal: Increased serum creatinine (33%)
Respiratory: Cough (11%), dyspnea (43%), pulmonary disease (24%, including pulmonary congestion, rales, rhonchi), respiratory system disorder (11%, including acute respiratory distress syndrome, pulmonary infiltrates, respiratory failure)
Miscellaneous: Fever (29%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (<10%), cardiac arrhythmia (10%), ventricular tachycardia (<10%)
Gastrointestinal: Abdominal distention (10%)
Genitourinary: Anuria (<10%)
Hematologic & oncologic: Disseminated intravascular coagulation (<10%; grade 4: 1%)
Hepatic: Increased serum alkaline phosphatase (10%)
Nervous system: Coma (<10%), psychosis (<10%), stupor (<10%)
Renal: Acute kidney injury (<10%)
Respiratory: Apnea (<10%), rhinitis (10%)
<1%:
Cardiovascular: Bradycardia (grade 4), coronary artery disease (grade 4), endocarditis (grade 4), ischemic heart disease (grade 4), pericardial effusion (grade 4), phlebitis (grade 4), premature ventricular contractions (grade 4), second-degree atrioventricular block (grade 4), shock (grade 4), supraventricular cardiac arrhythmia (grade 4), syncope (grade 4), thrombosis (grade 4)
Dermatologic: Gangrene of skin and/or subcutaneous tissues (grade 4)
Endocrine & metabolic: Hyperuricemia (grade 4), respiratory acidosis (grade 4)
Gastrointestinal: Bloody diarrhea (grade 4), gastrointestinal hemorrhage (grade 4), hematemesis (grade 4), intestinal perforation (grade 4), pancreatitis (grade 4)
Hematologic & oncologic: Hemorrhage (grade 4)
Nervous system: Agitation (grade 4), hypothermia (grade 4), paranoid ideation (grade 4), peripheral neuropathy (grade 4), seizure (grade 4, including tonic-clonic seizure)
Ophthalmic: Mydriasis (grade 4), pupillary disease (grade 4)
Renal: Increased blood urea nitrogen (grade 4), kidney failure (grade 4), renal tubular necrosis (grade 4)
Respiratory: Asthma (grade 4), hemoptysis (grade 4), hyperventilation (grade 4), hypoventilation (grade 4), hypoxia (grade 4), pneumothorax (grade 4), pulmonary edema (grade 4)
Frequency not defined:
Cardiovascular: Bacterial endocarditis, capillary leak syndrome
Nervous system: Neurotoxicity
Postmarketing:
Cardiovascular: Cardiac tamponade, cardiomyopathy, hypertension, myocarditis
Dermatologic: Bullous pemphigoid, cellulitis, Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Diabetes mellitus, hyperglycemia, hyperthyroidism, hyponatremia, hypophosphatemia, hypothyroidism, thyroiditis
Gastrointestinal: Cholecystitis, colitis, exacerbation of Crohn disease, gastritis, intestinal obstruction
Hematologic & oncologic: Eosinophilia, febrile neutropenia, lymphocytopenia, neutropenia, retroperitoneal hemorrhage
Hepatic: Hepatitis, hepatosplenomegaly
Hypersensitivity: Anaphylaxis, angioedema
Local: Tissue necrosis at injection site
Nervous system: Cerebral hemorrhage, cerebral vasculitis, encephalopathy, extrapyramidal reaction, insomnia, myasthenia gravis (oculo-bulbar), neuralgia, neuritis, subarachnoid hemorrhage, subdural hematoma
Neuromuscular & skeletal: Arthritis (inflammatory), myopathy, myositis, rhabdomyolysis, systemic sclerosis
Ophthalmic: Optic neuritis
Renal: Glomerulonephritis (crescentic IgA)
Respiratory: Pneumonia
Known history of severe hypersensitivity to aldesleukin or any component of the formulation; patients with organ allografts; patients with significant cardiac (including abnormal 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), kidney, hepatic, or CNS impairment.
Concerns related to adverse effects:
• Capillary leak syndrome: Severe and life-threatening capillary leak syndrome (CLS) may occur with aldesleukin treatment and result in cardiac, pulmonary, kidney, or hepatic impairment, including fatal cases. Signs and symptoms of CLS include (but are not limited to) hypotension, dyspnea, edema, and hypoalbuminemia. CLS may begin immediately after treatment initiation. Do not administer aldesleukin to patients with significant cardiac, pulmonary, kidney, or hepatic impairment. Avoid concomitant administration of medications that may contribute to additive hypotension, kidney toxicity, or hepatic toxicity.
• Cardiopulmonary toxicity: Eosinophilic infiltration of cardiac and pulmonary tissue may occur with aldesleukin. In a scientific statement from the American Heart Association, interleukin-2 has been determined to be an agent that may either cause direct myocardial toxicity (rare) or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
• CNS toxicity: Treatment with aldesleukin may result in CNS toxicity (may be life-threatening); clinical manifestations may include altered mental status, speech difficulties, cortical blindness, limb or gait ataxia, hallucinations, agitation, obtundation, demyelinating polyneuropathy, and coma. Mental status may worsen for several days prior to recovery; permanent deficits have been reported. Radiological findings may include multiple and occasionally single cortical lesions on MRI (with evidence of demyelination). Aldesleukin may cause seizure; avoid use in patients with seizure disorder or abnormal CNS imaging. Patients should be evaluated and treated for CNS metastases prior to treatment.
• Hyperglycemia: Hyperglycemia and/or diabetes mellitus have been reported with aldesleukin.
• Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis, have occurred with aldesleukin treatment. Treatment with aldesleukin may result in infusion reactions; signs/symptoms include fever, chills, and/or rigors.
• Immune-mediated adverse reactions: Aldesleukin has been associated with exacerbation or new onset of autoimmune disease or inflammatory disorders; may be severe or fatal. Exacerbation of Crohn disease, colitis, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, bullous pemphigoid, myocarditis, myositis, and neuritis (including optic neuritis leading to blindness) have been reported following treatment with aldesleukin. Thyroid disease (hypothyroidism, biphasic thyroiditis, and thyrotoxicosis) may occur with aldesleukin treatment; the onset of hypothyroidism is usually 4 to 17 weeks after treatment initiation; may be reversible upon treatment discontinuation (Hamnvik 2011). Hypothyroidism may sometimes be preceded by hyperthyroidism.
• Infections: Aldesleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and an increased risk of disseminated infection, including sepsis and bacterial endocarditis.
• Kidney toxicity: Aldesleukin may cause serious kidney toxicity, including oliguria and kidney failure; preexisting kidney impairment and concomitant nephrotoxic agents may increase the risk of kidney toxicity.
Special populations:
• Transplant recipients: Aldesleukin may increase the risk of allograft rejection.
Other warnings/precautions:
• Contrast media: An acute/atypical array of symptoms resembling aldesleukin adverse reactions (fever, chills, nausea, vomiting, rash, pruritus, diarrhea, hypotension, edema, and oliguria) were observed within 1 to 4 hours after iodinated contrast media administration, usually when given within 4 weeks after aldesleukin treatment, although symptoms have also been reported several months after aldesleukin treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Proleukin: 22,000,000 units (1 ea)
No
Solution (reconstituted) (Proleukin Intravenous)
22000000 unit (per each): $6,661.76
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Proleukin: 22,000,000 units (1 ea)
IV: Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.
Administer aldesleukin in an inpatient hospital setting with access to an intensive care facility and specialists in cardiopulmonary and intensive care medicine.
Administer as IV infusion over 15 minutes. If diluted solution is refrigerated, allow solution to reach room temperature prior to administration. Do not administer using an in-line filter or coadminister with other medications through the same IV line.
Note: Recommendations for antiemetics use may vary: Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref). Aldesleukin is not included in the most updated pediatric classification of acute emetogenicity clinical practice guideline (Ref).
Parenteral: IV: Allow solution to reach room temperature prior to administration; infuse over 15 minutes; flush line before and after with D5W, particularly if maintenance IV line contains sodium chloride. Some protocols infuse as a continuous infusion (Ref).
Melanoma, metastatic: Treatment of metastatic melanoma in adults.
Renal cell carcinoma, metastatic: Treatment of metastatic renal cell carcinoma in adults.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Aldesleukin. Risk X: Avoid combination
CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Aldesleukin may increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Management: Consider using lower doses to minimize toxicity of this combination. Only coadminister aldesleukin and interferons (alfa) in patients in whom potential benefits outweigh the risk of severe toxicity. Monitor renal and cardiac function closely if combined. Risk D: Consider therapy modification
Iodinated Contrast Agents: Aldesleukin may enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Verify the patient is not pregnant prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to aldesleukin may cause fetal harm.
Capillary leak syndrome may occur in any patient. If this occurs during pregnancy, hypotension and decreased placental perfusion may result; monitor fetus and neonate.
It is not known if aldesleukin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant (including impaired immune function), breastfeeding is not recommended by the manufacturer.
Baseline: CBC with differential; blood chemistries, including electrolytes, kidney, and hepatic function tests; baseline cardiac ejection fraction; pulmonary function tests; thyroid function. Evaluate for baseline coronary artery disease and CNS impairment prior to treatment initiation. Verify pregnancy status in patients that could become pregnant.
Monitoring during therapy: CBC with differential, blood chemistries, including electrolytes, kidney and hepatic function (daily); thyroid function (thyroid-stimulating hormone every 2 to 3 months during aldesleukin treatment [Hamnvik 2011]); assessment of capillary leak syndrome (vital signs [temperature, pulse, BP, and respiration rate], weight, fluid intake, serum albumin, urine output). Monitor for signs/symptoms of capillary leak syndrome (hypotension, dyspnea, edema, and hypoalbuminemia), cardiopulmonary toxicity; CNS toxicity (mental status changes, speech difficulty, cortical blindness, limb or gait ataxia, hallucination, agitation, obtundation, demyelinating polyneuropathy, and coma), dermatologic toxicity, GI toxicity, hyperglycemia/diabetes mellitus, hypersensitivity/infusion related reaction, and infection.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Aldesleukin is a human recombinant interleukin-2 product which 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.
Distribution: Primarily into plasma, lymphocytes, lungs, liver, kidney, and spleen; Vd: 6.3 to 7.9 L (Whittington 1993)
Metabolism: Renal (metabolized to amino acids in the cells lining the proximal convoluted tubules of the kidney)
Half-life elimination: IV:
Children: Distribution: 14 ± 6 minutes; Elimination: 51 ± 11 minutes
Adults: Distribution: 13 minutes; Terminal: 85 minutes
Excretion: Urine (primarily as metabolites); Clearance: 268 mL/minute
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