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 >72 hr of intubation, pericardial tamponade, renal toxicity requiring >72 hr of dialysis, CNS dysfunction consisting of >48 hr of coma or psychosis, intractable seizures, bowel perforation or ischemia, or GI bleeding requiring surgical intervention;
Allograft organ transplantation (↑ risk of rejection).
OB: Pregnancy;
Lactation: Lactation.

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);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, hypotension, tachycardia, CAPILLARY LEAK SYNDROME, CARDIAC ARREST, HF, MI, myocardial ischemia, pericardial effusion, thrombosis

Derm: pruritus, EXFOLIATIVE DERMATITIS

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

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

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

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

Metab: hyperuricemia, weight gain

Neuro: STROKE

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

Misc: chills, fever

Interactions ⬆ ⬇

Drug-drug:

Corticosteroids may ↓ effectiveness; avoid concurrent use.
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 units/kg (0.037 mg/kg) every 8 hr for 14 doses. Cycle is repeated once after a 9-day rest period for 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: 22 million units/vial

Assessment ⬆ ⬇

Monitor vital signs, weight, and intake and output frequently throughout therapy.
Assess baseline ejection fraction and coronary artery disease status. Monitor ECG and BP continuously during infusion. If atrial fibrillation, supraventricular tachycardia, bradycardia requiring treatment or is recurrent or persistent, or ↓ systolic BP to <90 mmHg occurs, hold therapy until recovery to sinus rhythm and asymptomatic. If sustained ventricular tachycardia ≥5 beats, uncontrolled or unresponsive arrhythmia, ECG changes consistent with ischemia, MI, or angina occurs, permanently discontinue aldesleukin.
Assess for signs/symptoms of capillary leak syndrome (hypotension, hypovolemia, edema, ascites, pleural effusions, ↓ urine output) immediately upon initiation and throughout therapy. If failure to maintain organ perfusion occurs, treat as indicated.
Assess baseline pulmonary function tests and monitor respiratory status and pulse oximetry frequently during and for a few weeks after last dose. If oxygen saturation <90% occurs, hold therapy until oxygen saturation >90%. If therapy-related intubation >72 hr occurs, permanently discontinue aldesleukin.
Assess baseline mental status and monitor for CNS impairment during therapy. If confusion, agitation or lethargy occurs, hold therapy until resolved. If coma or toxic psychosis >48 hr, or repeat or difficult to control seizure occurs, permanently discontinue aldesleukin.
Assess frequently for signs/symptoms of infection, including sepsis. Consider antibiotic prophylaxis for patients with central lines. If sepsis occurs, hold therapy until resolved, patient is clinically stable and infection is being treated.
Monitor for symptoms of stomatitis, and persistent nausea, vomiting or diarrhea. If fecal immunochemical or fecal occult blood tests positive, hold therapy until negative. If bowel ischemia/perforation or GI bleed requiring surgery occurs, permanently discontinue aldesleukin.
Monitor for immune-mediated adverse reactions (new onset or exacerbation of pre-existing autoimmune or inflammatory disease), including exfoliative dermatitis. Treat specific reactions, as indicated. If bullous dermatitis or marked worsening of pre-existing skin condition occurs, hold therapy until all signs of condition resolved.

Lab Test Considerations:

Verify negative pregnancy status prior to initiating therapy.
Monitor renal function. Assess serum creatinine at baseline and daily during therapy. If serum creatinine >4.5 mg/dL or ≥4 mg/dL with severe volume overload, acidosis, or hyperkalemia occurs, hold therapy until <1.5 mg/dL or baseline and fluid and electrolyte status stable. If persistent oliguria, urine output <10 mL/hr for 16–24 hr with ↑ serum creatinine occurs, hold therapy until urine output >10 mL/hr with ↓ of serum creatinine >1.5 mg/dL or serum creatinine normalization. If renal failure requiring dialysis >72 hr occurs, permanently discontinue aldesleukin.
Monitor CBC with differential and electrolytes at baseline and daily during therapy. May cause anemia, thrombocytopenia, hypomagnesemia, acidosis, hypocalcemia, hypophosphatemia, hypokalemia, hyperglycemia, hyperuricemia, hypoalbuminemia, and hypoproteinemia.
- Assess hepatic function at baseline and daily during therapy. May ↑ bilirubin, AST, ALT, and alkaline phosphatase. If liver pain or Grade ≥3 AST or ALT ↑ occurs, hold therapy for that course; resume new course ≥7 wk after signs of hepatotoxicity resolved and hospital discharge.
- Monitor thyroid function periodically during therapy.

Implementation ⬆ ⬇

High Alert: 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.
- Premedicate with an antipyretic, antibiotic and medication for GI irritation/bleeding per institutional guidelines. Additional premedications may be needed for hypotension, dyspnea, rigors, diarrhea, pruritus and dermatitis.
- Evaluate response 4 wk after treatment course completion and again immediately prior to scheduled start of the next course.

IV Administration:

Intermittent Infusion:
Reconstitution: Reconstituted each vial with 1.2 mL sterile water for injection. Direct sterile water at the side of the vial 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. Concentration: 18 million units (1.1 mg)/mL. Diluent: Dilute reconstituted solution in 50 mL of D5W.
- .
Rate: Infuse each dose over 15 min. Do not use an in-line filter during administration
Y-Site Compatibility:
- amikacin
- amphotericin B deoxycholate
- calcium gluconate
- diphenhydramine
- fluconazole
- foscarnet
- gentamicin
- magnesium sulfate
- metoclopramide
- morphine
- ondansetron
- tobramycin
- trimethoprim/sulfamethoxazole
- vancomycin
Y-Site Incompatibility:
- fluorouracil
- ganciclovir
- lorazepam
- pentamidine
- prochlorperazine
- promethazine
- rituximab
- trastuzumab

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications. Caution patient not to drink alcohol or take aspirin or NSAIDs during therapy.
Advise patient of risk of capillary leak syndrome and to notify healthcare professional immediately if new or worsening hypotension, dyspnea, or edema occurs.
Advise patient of risk of neurotoxicity and to notify healthcare professional immediately if mental status change, speech difficulties, blindness, ataxia, hallucination, agitation, or seizure occurs.
Advise patient of risk for immune-mediated reactions and exacerbation of pre-existing autoimmune disease affecting any organ or tissue, and to notify health care professional for new or worsening signs and symptoms.
Instruct patient to notify health care professional if rash, 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, electric razor and to avoid falls.
Advise patient to notify health care professional if stomatitis (sores along GI tract) or persistent diarrhea or vomiting occurs.
Inform patient that eye disorders may begin shortly after administration, persisting for several weeks, but are reversible.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Advise women of reproductive potential to use an effective 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 ⬆ ⬇