denileukin diftitox

den-i-LOOK-inDIF -ti-tox

Therapeutic Classification: antineoplastics

Pharmacologic Classification: cytotoxic proteins

High Alert

Relapsed or refractory stage I–III cutaneous T-cell lymphoma in patients who have received ≥1 prior systemic therapy.

A fusion protein that contains parts of diphtheria toxin fused to interleukin (IL)-2. Directs cytocidal action of diphtheria toxin to cells/tumors with IL-2 receptors.

Therapeutic effects:

Regression of cutaneous T-cell lymphoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Not extensively distributed to tissues.

Metabolism/Excretion: Metabolized by proteolytic breakdown.

Half-Life: 70–80 min.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

CV: capillary leak syndrome, edema

Derm: pruritus, rash, skin infection

EENT: blurred vision, loss of color vision

GI: ↑liver enzymes, constipation, diarrhea, HEPATOTOXICITY, nausea, vomiting

GU: ↓fertility (males), renal impairment

Hemat: anemia, lymphopenia

Metab: ↓appetite, hypoalbuminemia, weight gain

MS: ↑creatinine kinase, arthralgia, myalgia

Neuro: dizziness, fatigue, headache, insomnia, mental status changes

Misc: chills, fever, infusion-related reactions

Drug-drug:

None reported.

IV (Adults ): 9 mcg/kg/day for 5 consecutive days every 21 days; continue until disease progression or unacceptable toxicity.

Lyophilized powder for injection: 300 mcg/vial

Monitor for infusion-related reaction (nausea, fatigue, chills, fever, arthralgia). For Grade 2 or 3, interrupt infusion and manage clinically; premedicate with dexamethasone 4 mg (or equivalent) slow IV push for at least the next 3 cycles. For recurrent Grade 3 or Grade 4, permanently discontinue denileukin.
Monitor weight and BP for signs of capillary leak syndrome (hypotension, edema) routinely within 2 wk of infusion and after therapy stops as indicated. For Grade 2, hold denileukin until resolved to Grade 1. For Grade 3, hold and provide supportive care until resolved to Grade 1. Resume by ↓ dose by 50% and consider premedication with corticosteroid. For recurrent Grade 3 or Grade 4, permanently discontinue denileukin.
Provide for baseline ophthalmic exam and monitor visual acuity, color vision, and blurred vision as indicated throughout therapy. For Grade 1 or 2, hold or discontinue denileukin and refer for ophthalmic exam. For Grade 3 or 4, hold until resolved to ≤Grade 1, refer for ophthalmic exam, and permanently discontinue denileukin if does not resolve to ≤Grade 1.
Monitor bowel function and fluid status. May cause diarrhea, vomiting, and anorexia, leading to dehydration.
Assess for rash throughout therapy. May require antihistamines or topical or oral corticosteroids.

Lab Test Considerations:

Before administration, test malignant cells for CD25 expression. Verify negative pregnancy test prior to initiation of therapy.
- Monitor hepatic enzymes and bilirubin at baseline and as indicated during therapy for signs of hepatotoxicity. If ALT/AST 3–5 times upper limit of normal (ULN), maintain dose; monitor at least weekly until <3 times ULN. If ALT/AST >5–20 times ULN, hold until <3 times ULN; then resume at same dose or ↓ dose by 50% for subsequent occurrence. If ALT/AST >20 times ULN, permanently discontinue denileukin.
- Monitor CBC as indicated. May cause anemia and lymphopenia.
- Monitor serum albumin levels before initiation of each course and as clinically indicated. May cause hypoalbuminemia, with nadir occurring 1–2 wk after administration. Delay therapy until serum albumin ≥3 g/dL.

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. Administer only in settings equipped to provide cardiopulmonary resuscitation and close monitoring of patients.
Premedication: ≥30 min prior to infusion for Cycles 1–3 and as clinically indicated, administer acetaminophen, diphenhydramine, and antiemetic per institutional dosing guidelines, and hydrate with 0.9% NaCl 250–500 mL (or clinically appropriate volume) IV.

IV Administration:

Intermittent Infusion: Reconstitution: Bring vial(s) to room temperature over 30 min. Inject 2.1 mL sterile water for injection into each vial. Use separate syringe and needle for each vial if needed. Gently swirl; do not shake vial. Discard if solution is not clear and colorless or contains particulates. Dilute solution immediately.Diluent: Withdraw calculated dose from reconstituted vial(s) with plastic sterile syringe and inject into empty soft plastic (do not use glass) IV bag. Dilute with 0.9% NaCl to final concentration. Do not use if solution is cloudy or contains particulates. Use immediately or store diluted at room temperature for 4 hr. Protect from light.Concentration: 15 mcg/mL during all steps of preparation for infusion. Do not use in-line filter; discard any unused portion.
Rate: Infuse over 60 min.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Advise patient to perform daily weights and notify health care professional immediately if capillary leak syndrome (edema, ↑ BP, weight gain) occur.
Advise patient to notify health care professional promptly of visual changes, infusion reaction symptoms, easy bruising or bleeding, or signs of hepatotoxicity (fatigue, anorexia, jaundice, dark urine, right abdominal pain).
Caution patient to avoid crowds and use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during treatment and for 7 days following the last dose and to not breastfeed during therapy.

Regression of cutaneous T-cell lymphoma.

Lymphir

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Action ⬆ ⬇

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Assessment ⬆ ⬇

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US Brand Names ⬆