Aldesleukin

Name: Aldesleukin

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

  • seizures
  • fast or irregular heartbeat
  • coma
  • decreased urination
  • swelling of the face, arms, hands, feet, ankles, or lower legs
  • unusual tiredness or weakness
  • stomach pain
  • vomit that is bloody or looks like coffee grounds
  • blood in the stool
  • black and tarry stools

Is aldesleukin safe to take if I'm pregnant or breastfeeding?

It is not known whether aldesleukin can cause harm to the fetus. Because of it known side effects, the manufacturer recommends that it only be given to pregnant women using extreme caution.

It is not known whether aldesleukin is excreted in breast milk. Because of it known side effects, the manufacturer recommends that it only be given to pregnant women using extreme caution.

What else should I know about aldesleukin?

What preparations of aldesleukin are available?

Vials containing 22 million IU (international units) of aldesleukin as a lyophilized (freeze-dried) powder, with diluent.

How should I keep aldesleukin stored?

The vials should be stored in a refrigerator at 2 C to 8 C (36 F to 46 F ) before and after reconstitution with diluent. The vials should not be frozen. The solution should be brought to room temperature prior to infusion and used within 48 hours of reconstitution. Since the vials do not contain a preservative, any unused portion must be discarded.

Other problems associated with capillary leak include congestion in the lungs, difficulty breathing (which can occur in one-half of patients), wheezing, respiratory failure (1 out of every 11 patients), and swelling due to fluid accumulation in various tissues in the body (half of all patients). Abnormal heart rhythms occur in 1 out of every 12 patients, and heart attacks in 1 out of every 50. Bleeding from the stomach, intestines, and kidney or liver damage also can occur. Moreover, between two-thirds and three-fourths of all patients receiving aldesleukin develop kidney damage. Most of the side effects caused by capillary leak begin to resolve a few hours after stopping aldesleukin therapy.

Three-fourths of all patients receiving aldesleukin have mental changes including paranoia and hallucinations. Drowsiness, sleep disturbances, headache, fatigue, weakness, malaise, loss of appetite, visual changes, and alterations or loss of taste sensation also occur.

Between 20% and 50% of patients develop hypothyroidism (low thyroid hormone) which usually requires replacement with thyroid drugs, for example, levothyroxine (Synthroid; Levoxyl). Anemia occurs in 3 out of every 4 patients and may necessitate blood transfusions. A low platelet count (increasing the risk of bleeding) occurs in two-thirds of patients, and low white blood cell count in one-third. Infection may occur in one-quarter of treated patients and possibly lead to death. Itching occurs in half of all patients and rash in one-quarter. Occasionally, rashes can be severe. Generalized pain occurs in one-half of all patients. Gastrointestinal side effects occur frequently. Nausea or vomiting occur in 7 out of every 8 patients, diarrhea in 3 out of every 4, ulcerations of the mouth in 1 out of every 3, and abdominal pain or constipation in less than 1 out of every 10. Liver tests become abnormal in 3 out of every 5 persons who receives aldesleukin and jaundice in 1 out of every 9.

Aldesleukin Drug Class

Aldesleukin is part of the drug class:

  • Interleukins

What is aldesleukin?

Aldesleukin is a cancer medication that interferes with tumor growth.

Aldesleukin is used to treat kidney cancer or skin cancer than has spread to other parts of the body.

Aldesleukin may also be used for purposes not listed in this medication guide.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving aldesleukin?

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Cautions for Aldesleukin

Contraindications

  • Known history of hypersensitivity to IL-2 or any ingredient in the formulation.1

  • Abnormal thallium stress test results.1

  • Abnormal pulmonary function test results.1

  • Organ allografts.1

  • Further therapy contraindicated if certain toxicities developed during previous aldesleukin therapy (i.e., sustained ventricular tachycardia [≥5 beats], uncontrolled cardiac arrhythmias or arrhythmias unresponsive to management, chest pain with ECG changes consistent with angina or MI, cardiac tamponade, intubation for >72 hours, renal failure requiring dialysis for >72 hours, coma or toxic psychosis lasting >48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, or GI bleeding requiring surgery).1 (See Dosage Modification for Toxicity and Contraindications for Retreatment under Dosage and Administration.)

Warnings/Precautions

Warnings

Patient Selection

Careful patient selection mandatory prior to initiation of drug, including assessment of cardiac, renal, hepatic, CNS, and pulmonary functions, blood chemistry, and blood cell counts.1 (See Boxed Warning and also see Toxicity and Adequate Patient Monitoring under Cautions.)

However, even patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience adverse events.1 Adverse effects are frequent, often serious, and sometimes fatal.1 6 15 20 Carefully weigh risks versus benefits of therapy.1 15 6 20 (See Contraindications under Cautions.)

Patients with favorable Eastern Cooperative Oncology Group performance status (ECOG PS 0) at treatment initiation have a higher response rate and lower toxicity; therefore, consider performance status during patient selection for treatment.1 111 112 Experience in patients with ECOG PS >1 extremely limited.1

Autoimmune and Inflammatory Reactions

Possible development or exacerbation of autoimmune disease and inflammatory disorders when used alone or in combination with interferon alfa.1 (See Specific Drugs under Interactions.)

Possible onset of symptomatic hyperglycemia and/or diabetes mellitus.1

Possible hypothyroidism, sometimes preceded by hyperthyroidism, following treatment; may require thyroid hormone replacement therapy.1 Hyperthyroidism also reported.1

Increased risk of allograft rejection in transplant patients because of enhanced cellular immune function.1

Exacerbation of Crohn’s disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, and bullous pemphigoid reported.1

CNS Effects

Thoroughly evaluate and treat all patients for CNS metastases; must have a negative CT scan prior to receiving therapy.1

New neurologic manifestations (e.g., mental status changes, speech difficulties, cortical blindness, limb/gait ataxia, hallucinations, agitation, obtundation, coma) and anatomic lesions reported following aldesleukin therapy in patients without evidence of CNS metastases.1 6 8 9 15 20

Mental status changes (e.g., irritability, confusion, depression, agitation, lethargy, somnolence) may be a direct result of CNS toxicity from aldesleukin or indicative of bacteremia, early bacterial sepsis, hypoperfusion, or occult CNS malignancy.1 Aldesleukin-induced mental status changes generally reverse within several days after discontinuance of the drug,15 although may progress for several days before recovery begins.1 15 101 However, permanent neurologic defects reported.1

Potential for seizures; use with extreme caution if known seizure disorders.1

Sensitivity Reactions

Risk of anaphylaxis in patients receiving various treatment regimens that included aldesleukin.1

Hypersensitivity reactions (e.g., erythema, pruritus, hypotension) reported within hours of administration of therapy in patients receiving combination regimens with sequential administration of high-dose aldesleukin and antineoplastic agents (specifically cisplatin, dacarbazine, tamoxifen, and interferon alfa);1 medical intervention required in some patients.1 (See Specific Drugs under Interactions.)

Potential for nonanaphylactic allergic reactions.140

May predispose individuals to acute, atypical adverse reactions to iodinated radiographic contrast media.1 (See Specific Drugs under Interactions.)

Major Toxicities

Capillary Leak Syndrome

Risk of CLS particularly at usual dosages recommended by the manufacturer; risk of severe, possibly fatal, hypotension and reduced organ perfusion.1 6 8 11 15 101 Begins immediately after treatment initiation; characterized by increased vascular permeability to proteins and fluids and reduced vascular tone.1 6 15 (See Boxed Warning.)

Monitor fluid and organ perfusion status carefully; frequently monitor BP, heart rate, and organ function, including assessment of mental status and urine output.1 Assess hypovolemia by catheterization and central venous pressure monitoring.1

If hypovolemia occurs, administration of IV fluids (e.g., colloid replacement fluids or crystalloids) recommended.1 Use caution when administering large volumes of IV fluids to correct hypovolemia; unrestrained fluid administration may exacerbate complications associated with edema or effusions.1

Use extreme caution when treating patients with fixed requirements for large volumes of fluid (e.g., those with hypercalcemia); flexibility in fluid and vasopressor management is essential for maintaining organ perfusion and BP.1 101

Management of edema and ascites and/or effusions depends on careful balancing of fluid shifts to ensure that the consequences of hypovolemia (e.g., impaired organ perfusion) or fluid accumulation (e.g., pulmonary edema) do not exceed the patient’s tolerance.1

Early administration of IV dopamine with or without IV phenylephrine hydrochloride before onset of hypotension can help maintain organ perfusion, particularly renal perfusion, and preserve urine output.1 Exercise caution; prolonged use of vasopressors, alone or in combination, at relatively high doses may be associated with cardiac rhythm disturbances.1

If adequate organ perfusion not maintained (demonstrated by altered mental status, reduced urine output, decrease in SBP to <90 mm Hg, or onset of cardiac arrhythmias), withhold subsequent aldesleukin doses until organ perfusion recovers and SBP ≥90 mm Hg.1

Recovery from CLS begins within a few hours after discontinuance of aldesleukin therapy.1 If excessive weight gain, edema or pulmonary congestion with shortness of breath occurs, diuretics may hasten recovery once BP normalized.1

Flu-like Syndrome

Flu-like syndrome (e.g., fever [sometimes grade 4 or life-threatening], chills, rigors) possible.1 6 13 15 Other symptoms possible (e.g., pain,1 abdominal pain,1 malaise,1 asthenia, 1 arthralgia and/or myalgia, 15 140 chest pain,140 back pain,140 fatigue).140

General Precautions

Toxicity and Adequate Patient Monitoring

Highly toxic drug; prior to initiation of therapy and daily during therapy, perform hematologic tests (e.g., CBC, differential, platelet counts), blood chemistries (e.g., serum electrolyte concentrations), renal and hepatic function tests, and chest radiographs.1 (See Cardiovascular Effects, Pulmonary Effects, Renal Impairment, and Hepatic Impairment, all under Cautions.)

During therapy, monitor vital signs (i.e., temperature, pulse, BP, respiration rate) at least every 4 hours52 and patient’s weight and fluid intake and output daily.1 52 In hypotensive patients, monitor vital signs hourly.1 If SBP decreases (especially to <90 mm Hg), perform constant cardiac rhythm monitoring.1 (See Cardiovascular Effects under Cautions.)

Cardiovascular Effects

Prior to initiation of therapy, perform a stress thallium study to document normal cardiac ejection fraction and unimpaired myocardial wall motion.1 101 If results suggest minor wall motion abnormalities, test further to exclude CAD.1 (See Boxed Warning.)

During therapy, assess cardiac function daily.1 If signs or symptoms (e.g., chest pain, murmurs, gallops, irregular cardiac rhythm, palpitation), assess with an ECG and cardiac enzymes.1 Evidence of myocardial injury, including findings compatible with MI or myocarditis, reported.1 Ventricular hypokinesia caused by myocarditis may persist for several months.1 If evidence of cardiac ischemia or CHF, withhold therapy and repeat thallium study.1

Pulmonary Effects

Perform baseline pulmonary function tests with arterial blood gases in all patients.1 Must have adequate pulmonary function (FEV1 >2 L or >75% of predicted value based on height and age) prior to initiation of therapy.1

Monitor pulmonary function regularly during therapy.1 If dyspnea or clinical signs of respiratory impairment (i.e., tachypnea or rales), assess with arterial blood gases.1 Repeat as often as clinically indicated.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether aldesleukin is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Response, median number of doses per course, and median number of courses of therapy in patients ≥65 years of age does not appear to differ from that in younger adults; however, possible increased risk of toxicity in patients with renal impairment.1 Possible increased incidence of severe urogenital toxicity and dyspnea compared with younger patients.1

Hepatic Impairment

Aldesleukin therapy impairs hepatic function.1 Normal hepatic function necessary at start of therapy.1 (See Toxicity and Adequate Patient Monitoring under Cautions and also see Hepatotoxic Agents under Interactions.)

Renal Impairment

Contraindicated in patients who develop renal impairment requiring dialysis for >72 hours after a previous course of aldesleukin.1

Aldesleukin therapy impairs renal function.1 Preexisting renal impairment appears to be associated with an increased risk of more severe and prolonged renal dysfunction.10 15 (See Toxicity and Adequate Patient Monitoring under Cautions and also see Nephrotoxic Agents under Interactions.)

Manufacturer states that Scr should be≤1.5 mg/dL prior to initiation of aldesleukin therapy.1

Common Adverse Effects

Hypotension, diarrhea, renal dysfunction with oliguria, chills, vomiting, dyspnea, rash, bilirubinemia, thrombocytopenia, nausea, confusion, increased Scr, anemia, fever, peripheral edema, malaise, lung disorders (e.g., pulmonary congestion, rales, rhonchi), pruritus, asthenia, tachycardia, increased AST, stomatitis, somnolence, anorexia.1

Life-threatening or grade 4 adverse effects: Renal dysfunction with oliguria/anuria, hypotension, respiratory disorder (i.e., ARDS, respiratory failure, intubation), coma, bilirubinemia.1

Interactions for Aldesleukin

Cardiotoxic Agents

Concurrent administration may increase risk of cardiotoxicity.1

CNS-Active Agents

Concurrent administration may increase risk of CNS effects.1

Hepatotoxic Agents

Concurrent administration may increase risk of hepatotoxicity. (See Hepatic Impairment under Cautions.)1

Myelotoxic Agents

Concurrent administration may increase risk of myelotoxicity.1

Nephrotoxic Agents

Concurrent administration may increase risk of nephrotoxicity. (See Renal Impairment under Cautions.)1

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

Possible increase in nephrotoxicity1

Anthracyclines (e.g., doxorubicin)

Possible increase in cardiotoxicity1

Antihypertensive agents (e.g., β-blocking agents)

Possible increase in hypotensive effects1

Antineoplastic agents

Possible increased myelotoxicity1

Safety and efficacy not established1

Asparaginase

Possible increase in hepatotoxicity1

Cisplatin

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

CNS depressants (e.g., analgesics, antiemetics, opiate agonists, sedatives, tranquilizers)

Possible increased risk of CNS effects1

Corticosteroids (glucocorticoids)

Possible reduction of antitumor effectiveness1

Avoid concomitant use1

Dacarbazine

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

Indomethacin

Possible increase in nephrotoxicity1

Interferon alfa

Possible development or exacerbation of autoimmune disease and inflammatory disorders (e.g., thyroiditis,1 inflammatory arthritis,1 oculo-bulbar myasthenia gravis,1 crescentic IgA glomerulonephritis,1 155 Stevens-Johnson syndrome,1 or bullous pemphigoid)1

Possible increased incidence of myocardial injury (MI,1 myocarditis,1 ventricular hypokinesia,1 and severe rhabdomyolysis)1

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

Methotrexate

Possible increase in hepatotoxicity1

Roentgenographic agents

Potential acute, atypical adverse reactions (e.g., fever, chills, nausea, vomiting, diarrhea, pruritus, rash, hypotension, edema, oliguria)1 to iodinated radiographic contrast media 1

May occur when contrast media are administered up to several months after aldesleukin administration1

Tamoxifen

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

Advice to Patients

  • Risk of serious, life-threatening, or fatal adverse effects in patients with normal cardiovascular, pulmonary, hepatic, or CNS function.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular or pulmonary disease).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

How is this medicine (Aldesleukin) best taken?

Use aldesleukin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given into a vein for a period of time.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

Pronunciation

(al des LOO kin)

Dosage Forms

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)

Administration

Aldesleukin doses >12 to 15 million units/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis, 2011).

Administer as IV infusion over 15 minutes (do not administer with an inline filter). Allow solution to reach room temperature prior to administration. Flush before and after with D5W, particularly if maintenance IV line contains sodium chloride. Some off-label uses/doses are infused as a continuous infusion (Legha, 1998; Yu, 2010). Has also been administered by SubQ injection (off-label route).

Pregnancy & Lactation

Pregnancy Category: C

Lactation: excretion in milk unknown/not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

In Summary

Commonly reported side effects of aldesleukin include: supraventricular tachycardia, adult respiratory distress syndrome, congestive heart failure, exfoliative dermatitis, infection, pulmonary congestion, pulmonary infiltrates, respiratory tract disease, cardiac arrhythmia, edema, abdominal pain, acidosis, altered blood pressure, anemia, anxiety, asthenia, asymptomatic ecg changes, cardiovascular disorder, confusion, diarrhea, dizziness, drowsiness, dyspnea, enlargement of abdomen, fever, hyperbilirubinemia, hypocalcemia, hypomagnesemia, hypotension, increased cough, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum creatinine, leukopenia, nausea, oliguria, pain, peripheral edema, pruritus, pulmonary disease, rales, rhinitis, rhonchi, skin rash, stomatitis, tachycardia, thrombocytopenia, vasodilatation, vomiting, weight gain, anorexia, chills, and malaise. See below for a comprehensive list of adverse effects.

Dose Adjustments

No adjustment recommended; however, use caution as the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

For Renal Toxicity:
-Decisions to stop, hold, or restart treatment should be made after performing a global patient assessment; dose reductions are not recommended.
-Life-threatening toxicities may be ameliorated with IV dexamethasone, which may also cause aldesleukin to lose its therapeutic effects.
-Retreatment is contraindicated in patients who have experienced these toxicities.

-HOLD DOSE: Serum creatinine greater than 4.5 mg/dL or 4 mg/dL or greater in the presence of severe volume overload, acidosis, or hyperkalemia; persistent oliguria, urine output of less than 10 mL/hr for 16 to 24 hours with rising SCr.
-RESTART DOSE: SCr less than 4 mg/dL and stable fluid and electrolyte status; urine output greater than 10 mL/hr with a decrease of SCr greater than 1.5 mg/dL or normalization of SCr.

Aldesleukin Pregnancy Warnings

Use is recommended only if the potential benefit justifies the possible fetal risk. US FDA pregnancy category: C Comments: -Sexually active women and men should use effective contraception during treatment. -This drug should not be administered to fertile persons of either gender who are not practicing effective contraception.

Animal studies have revealed evidence of embryolethality at doses 27 to 36 times the human dose, and significant maternal toxicities at doses 2.1 to 36 times the human dose. No teratogenicity has been observed other than that attributed to maternal toxicity. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

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