aldesleukin

Contraindicated in:

Hypersensitivity to aldesleukin or mannitol;
Cross-sensitivity to
Escherichia coli—
derived proteins may occur;
History of cardiac or pulmonary disease as assessed by abnormal thallium stress testing or abnormal pulmonary function testing;
Patients who have experienced any of the following toxicities during previous courses of aldesleukin—sustained ventricular tachycardia (≥5 beats), angina pectoris or MI as indicated by ECG changes, respiratory problems requiring more than 72 hr of intubation, pericardial tamponade, renal toxicity requiring more than 72 hr of dialysis, CNS dysfunction consisting of more than 48 hr of coma or psychosis, intractable seizures, bowel perforation or ischemia, GI bleeding requiring surgical intervention;
Patients who have had allograft organ transplantation (↑ risk of rejection).

Use Cautiously in:

History of cardiovascular, respiratory, hepatic, or renal disease;
History of seizures or suspected CNS metastases (symptoms may be exaggerated and seizures may occur);
Patients with child-bearing potential;
OB: Safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, hypotension, tachycardia, HF, MI, CARDIAC ARREST, myocardial ischemia, pericardial effusion, STROKE, thrombosis

Derm: pruritus, EXFOLIATATIVE DERMATITIS

F and E: acidosis, hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hyperuricemia, hyponatremia, metabolic alkalosis

GI: diarrhea, jaundice, nausea, stomatitis, vomiting, ascites, BOWEL PERFORATION, hepatomegaly

GU: oliguria/anuria, proteinuria, dysuria, hematuria, renal failure

Hemat: anemia, coagulation disorders, leukopenia, thrombocytopenia, eosinophilia, leukocytosis

Resp: dyspnea, pulmonary congestion, pulmonary edema, APNEA, hemoptysis, pleural effusion, pneumothorax, RESPIRATORY FAILURE, tachypnea, wheezing

Misc: chills, fever, CAPILLARY LEAK SYNDROME, weight gain, weight loss

Interactions ⬆ ⬇

Drug-drug:

Corticosteroids decrease antineoplastic effectiveness. Avoid concurrent use with aldesleukin.
Additive hypotension may occur with antihypertensives.
Concurrent cardiotoxic, hepatotoxic, myelotoxic, or nephrotoxic drug therapy↑ the risk of toxicity in these organs.

Route/Dosage ⬆ ⬇

IV (Adults ): 600,000 IU/kg (0.037 mg/kg) every 8 hr for 14 doses. Cycle is repeated once after a 9-day rest period to a total of 28 doses. After a rest period of 7 wk, patients who have had a beneficial response may be evaluated for additional courses.

Availability ⬆ ⬇

Powder for injection (requires reconstitution): 22 million units/vial

Assessment ⬆ ⬇

Monitor ECG continuously during infusion. Cardiac function, including thallium stress testing, should be determined prior to initiation of therapy. Supraventricular arrhythmias may respond to digoxin or verapamil and usually resolve after completion of therapy.
Monitor vital signs at least daily throughout therapy. Fever, chills, rigors, and malaise usually occur within hours of administration. Acetaminophen and an NSAID, such as indomethacin, should be administered prior to initiation of aldesleukin therapy to reduce fever. Meperidine may be given to control rigors associated with fever.
Assess patient for the development of capillary leak syndrome (hypotension, hypovolemia, edema, ascites, pleural effusions). This initially manifests as a drop in arterial BP beginning 2–12 hr from start of administration. If BP decreases to <90 mmHg, constant ECG monitoring, hourly vital signs, and CVP monitoring are recommended.
Monitor respiratory status and pulse oximetry frequently. Pulmonary function tests, including arterial blood gases, and chest x-ray should be monitored prior to and periodically throughout therapy. Pulmonary toxicity (respiratory failure, tachypnea, wheezing) and pulmonary infiltration may become apparent by the 4th day of therapy and usually resolve within a few wk after therapy. Respiratory failure may require intubation.
Monitor weight daily. Weight gain during therapy may be more than 10% of pretreatment weight. Reversal of weight gain, via diuresis of fluid, may take up to 1–2 wk after therapy.
Monitor for changes in mental status. Hold administration if patient develops moderate-to-severe lethargy or somnolence. Low doses of haloperidol have been used for debilitating mental status changes.
Assess frequently for signs of infection, particularly sepsis and bacterial endocarditis. Antibiotic prophylaxis directed against
Staphylococcus aureus
may be used for patients with central lines. Any intercurrent infections should be managed aggressively. Aldesleukin impairs the function of WBCs.
Assess for signs of anemia (increased fatigue, dyspnea, orthostatic hypotension) and bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis). Cimetidine may be given for prophylaxis of GI irritation and bleeding. Transfusions of RBCs and/or platelets may be required.
Assess nutrition and bowel status. Stomatitis may require a liquid diet or initiation of parenteral nutrition. Nausea, vomiting, and diarrhea occur in most patients and may lead to hypokalemia and acidosis. Antiemetics and antidiarrheals may be given as needed and are usually discontinued 12 hr after last dose.
Assess skin daily for rash or blisters on skin. Notify health care professional if these occur; exfoliative dermatitis can be fatal.

Lab Test Considerations:

Monitor CBC, differential, platelet count, blood chemistries including electrolytes, and renal and hepatic function prior to and daily throughout therapy. May cause elevated bilirubin, BUN, serum creatinine, transaminase, and alkaline phosphatase levels. May cause anemia, thrombocytopenia, hypomagnesemia, acidosis, hypocalcemia, hypophosphatemia, hypokalemia, hyperuricemia, hypoalbuminemia, and hypoproteinemia.
- Monitor thyroid function periodically during therapy.

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings.
- Aldesleukin should be administered only in a hospital setting with intensive care facilities.

IV Administration:

Intermittent Infusion: Reconstitute each vial with 1.2 mL of sterile water for injection. Concentration: 18 million IU (1.1 mg)/mL. Direct the sterile water at the side of the vial during reconstitution and swirl contents gently to prevent excessive foaming. Do not shake. Solution should be clear and colorless to slightly yellow. Administer within 48 hr of reconstitution. Discard unused portion.
- Diluent: Dilute reconstituted dose in 50 mL of D5W. Do not reconstitute or dilute with bacteriostatic water for injection, 0.9% NaCl, or albumin.
- Do not use an in-line filter during administration of aldesleukin.
Rate: Infuse each dose over 15 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to notify health care professional if dyspnea, sore throat, fever, chills, yellow skin, unusual bleeding or bruising, or fatigue occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use a soft toothbrush and electric razor and to be especially careful to avoid falls. Patients should be cautioned not to drink alcohol or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
Inform patient that visual problems usually begin shortly after aldesleukin administration and may persist for several wk but are reversible.
Advise patient to use a nonhormonal method of contraception throughout therapy.

ROUTE	ONSET	PEAK	DURATION
IV	4 wk	unknown	12 mo

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇