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Denileukin Diftitox

Pronunciation: (DEN-i-LOO-kin DIF-ti-tox)
Class: Biologic response modifier

Trade Names:
Ontak
- Injection, solution, concentrate 150 mcg/mL

Pharmacology

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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.

Pharmacokinetics

Distribution

Distribution half-life approximately 2 to 5 min. Vd is 0.06 to 0.09 L/kg.

Metabolism

Metabolized by proteolytic degradation.

Elimination

Terminal half-life approximately 70 to 80 min. Cl approximately 0.6 to 2 mL/min/kg.

Indications and Usage

Treatment of persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.

Unlabeled Uses

Treatment of chronic lymphocytic leukemia refractory to fludarabine; non-Hodgkin lymphoma.

Contraindications

Standard considerations.

Dosage and Administration

Cutaneous T-Cell Lymphoma
Adults

IV 1 treatment cycle is 9 or 18 mcg/kg/day administered for 5 consecutive days every 21 days for 8 cycles. Infuse over 30 to 60 min.

Dosage Adjustments Adults

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

General Advice

Administer by IV infusion 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 sodium chloride 0.9% for a final concentration of at least 15 mcg/mL. The denileukin diftitox concentration should not be less than 15 mcg/mL at any time during product preparation. Swirl vial gently to mix the solution. Do not shake vial.
Administer prepared solutions within 6 h, using a syringe pump or IV infusion bag.
Discard unused portions immediately.
Do not use glass containers.
Pretreat with an antihistamine and acetaminophen prior to each treatment.

Storage/Stability

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 h or at room temperature for 1 to 2 h. Do not heat denileukin. Do not refreeze.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (16%); capillary leak syndrome (11%).

CNS

Pyrexia (64%); fatigue (47%); headache (29%); asthenia (18%); dizziness (13%).

Dermatologic

Rash (24%); pruritus (18%).

EENT

Visual changes, including acuity (4%).

GI

Nausea (60%); vomiting (35%); diarrhea (22%); anorexia (20%); dysgeusia (11%).

Hepatic

Increased ALT or AST (84%).

Lab Tests

Evidence of denileukin neutralizing antibodies approached 100% after 3 courses of treatment.

Musculoskeletal

Rigors (47%); myalgia (20%); back pain (18%); arthralgia (16%).

Respiratory

Cough (20%); dyspnea, upper respiratory tract infection (13%).

Miscellaneous

Peripheral edema (26%); chest pain, pain (13%); infusion reactions (8%).

Precautions

Warnings

Infusion reactions

Serious and fatal infusion reactions have been reported. Administer in a facility equipped and staffed for cardiopulmonary resuscitation. If serious infusion reactions occur, immediately stop and permanently discontinue denileukin.

Capillary leak syndrome

Capillary leak syndrome resulting in death has been reported. Monitor weight, edema, BP, and serum albumin levels prior to and during treatment.

Visual acuity

Loss of visual acuity and color vision have been reported.

Monitor

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 weight, edema, and BP prior to and during treatment.

Pregnancy

Category C .

Lactation

Undetermined. Patients receiving denileukin should discontinue breast-feeding.

Children

Safety and efficacy not established.

Elderly

Clinical studies did not include sufficient numbers of subjects 65 yr of age and older to determine whether they respond differently from younger subjects.

Capillary leak syndrome

Occurs within 2 wk after starting therapy. Take special caution in patients with preexisting CV disease.

Overdosage

Symptoms

Chills, fever, moderate to severe nausea, persistent asthenia, vomiting.

Patient Information

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 BP 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: back pain; chest pain or tightness; difficulty breathing; difficulty swallowing; fainting; fever, chills, or other signs of infection; flushing; hives; rash; sores in mouth; swelling; unusual bleeding or bruising; visual loss or loss of color vision.
Advise patient, family, or caregiver to report any of the following to health care provider: pain, redness, or swelling at injection site; persistent nausea, vomiting, diarrhea or appetite loss; persistent or worsening general body weakness.