Denileukin Diftitox

Actions Denileukin, a recombinant DNA-derived cytotoxic protein fused to diphtheria toxin fragments A and B, is designed to direct the cytocidal action of diphtheria toxin to cells that express the IL-2 receptor. Following the first IV dose in lymphoma patients, denileukin displayed 2-compartment behavior with a distribution half-life of about 2 to 5 min and a terminal phase half-life of about 70 to 80 min. Volume of distribution was similar to that of circulating blood (0.06 to 0.08 L/kg). Systemic exposure was variable but proportional to dose. Denileukin is metabolized by proteolytic degradation.

 Indications Cutaneous T-cell lymphoma.

 Contraindications Standard considerations.

 Route/Dosage

Cutaneous T-Cell lLymphoma

ADULTS: IV 1 treatment cycle is 9 or 18 mcg/kg/day administered for 5 consecutive days q 21 days. Infuse over at least 15 min.

Pretreatment Regimen

ADULTS: Give acetaminophen 650 mg (PO or rectal) and diphenhydramine 25 to 50 mg (PO or IV) 30 to 60 min before administering denileukin diftitox.

Dosage Adjustments

ADULTS: Delay therapy in patients with serum albumin below 3 g/dL.

Interactions

Beta blockers, other antihypertensive

May exacerbate denileukin diftitox-induced hypotension.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Capillary leak syndrome; hypotension; edema; chest pain; tachycardia; thrombotic events; MI. CNS: Asthenia; headache; dizziness; paresthesia; nervousness; confusion; insomnia. DERMATOLOGIC: Rash; pruritus; injection site irritation. ENDOCRINE: Hypoalbuminemia; infection; impaired immune function; hypocalcemia; albuminuria. GI: Nausea; vomiting; elevated LFTs; anorexia; diarrhea; constipation; weight loss; dysphagia. GU: Hematuria; pyuria. HEMATOLOGIC: Anemia; thrombocytopenia; leukopenia. HYPERSENSITIVITY: Hypotension; dyspnea; vasodilation; rash; pruritis; anaphylaxis. METABOLIC: Dehydration. MUSCULOSKELETAL: Myalgia; arthralgia; pain. RENAL: Hematuria; pyuria; increased serum creatinine. RESPIRATORY: Dyspnea; cough increase; pharyngitis; rhinitis. OTHER: Chills; fever.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Patients receiving denileukin should discontinue nursing. Children: Safety and efficacy not established. Elderly: Anorexia, hypotension, anemia, confusion, rash, nausea, or vomiting tended to be more frequent or severe in patients at least 65 yr. Hypersensitivity: Acute hypersensitivity reactions were reported in 69% of patients during or within 24 hr of infusion; about 50% of the events occurred on the first day of dosing regardless of the treatment cycle. Vascular leak syndrome: Occurs within 2 wk after starting therapy. Take special caution in patients with preexisting cardiovascular disease.

 Administration/Storage

• Administer by IV use only. Do not administer as a bolus injection. Do not physically mix with other drugs. Do not administer through an in-line filter.
• Dilute the desired dose with 0.9% Sodium Chloride for a final concentration of at least 15 mcg/mL. The denileukin diftitox concentration should not be under 15 mcg/mL at any time during prouct preparation. Swirl vial gently to mix the solution. Do not shake vial.
• Administer prepared solutions within 6 hr, using a syringe pump or IV infusion bag.
• Discard unused portions immediately.
• Store frozen at no more than -10°C (14°F). Must be brought to room temperature, at no more than 25°C (77°F), before preparing the dose. The vials may be thawed in the refrigerator at 2° to 8°C (36° to 46°F) for no more than 24 hr or at room temperature for 1 to 2 hr. Do not heat denileukin. Do not refreeze.
• Do not use glass IV containers.

 Assessment/Interventions

• Denileukin diftitox should be used only by health care providers experienced in the use of antineoplatic therapy and management of patients with cancer. Manage patients treated with denileukin diftitox in a facility equipped and staffed for cardiopulmonary resuscitation and where the patient can be closely monitored for an appropriate period based on his or her health status.
• Prior to administration of this product, test the patient's malignant cells for CD25 expression.
• Perform a CBC and a blood chemistry panel, including liver and renal function and serum albumin levels, prior to initiation of treatment and weekly during therapy.
• Monitor serum albumin levels prior to the initiation of each treatment course. Delay administration until serum albumin levels are at least 3 g/dL.
• Carefully monitor weight, edema, BP, urine output, and serum albumin levels on an outpatient basis.
• Carefully monitor patients for infections.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver that home blood pressure measurements and weighing may be necessary. Instruct patient, family, or caregiver in proper technique if necessary.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; flushing; difficulty breathing; chest pain or tightness; back pain; difficulty swallowing; fainting; swelling; fever, chills, or other signs of infection; sores in mouth; unusual bleeding or bruising.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea or appetite loss; persistent or worsening general body weakness; pain, redness, or swelling at injection site.
• Instruct patient to not take any prescription or otc medications or dietary supplements unless advised to do so by health care provider.
• Instruct women of childbearing potential to notify health care provider if becoming pregnant, planning on becoming pregnant, or are breastfeeding.
• Advise patient that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.