Ontak

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Other drugs may interact with denileukin diftitox, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

• Eisai Oncology

• Eisai, Inc

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of this medication, there are no specific foods that you must exclude from your diet.

Before taking Ontak,

• tell your doctor and pharmacist if you are allergic to Ontak or any of the ingredients in Ontak. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended dose is 9 or 18 mcg/kg/day by injection over 30-60 minutes for 5 consecutive days every 21 days for 8 cycles.

Antineoplastic agent; recombinant DNA-derived cytotoxic protein.1

Contraindications

• Known hypersensitivity to denileukin diftitox, diphtheria toxin, aldesleukin (interleukin-2), or any other ingredient in the formulation.1

Warnings/Precautions

Warnings

Administer only under supervision of qualified clinicians experienced in use of cytotoxic therapy.1

Closely monitor patients in a setting equipped and staffed by health-care personnel appropriately trained in CPR.1

Risk of severe and/or fatal capillary leak syndrome (e.g., hypotension, edema, hypoalbuminemia).1 3 4

Syndrome usually occurs within the first 2 weeks of the infusion and may persist or worsen after completion of the treatment cycle.1 6

Use with caution in patients with preexisting cardiovascular disease and/or low serum albumin concentrations, since they appear to be at increased risk of developing this syndrome.1 3 6

Monitor weight, edema, BP, and serum albumin concentrations.1 Usually self-limiting; initiate treatment only if clinically indicated.1 6

Loss of visual acuity, usually with loss of color vision, reported; occurred with or without retinal pigment mottling.a b Although recovery was reported in some affected patients, most patients reported persistent visual impairment.a b

Sensitivity Reactions

Potentially fatal, acute hypersensitivity reactions (e.g., hypotension, dyspnea, anaphylaxis) reported in about 69% of patients during or within 24 hours of infusion; about 50% of cases occurred on the first day of dosing, regardless of the treatment cycle.1 3 4 8

If hypersensitivity reaction occurs, discontinue immediately and/or institute appropriate therapy as indicated (e.g., IV antihistamine, epinephrine, corticosteroids).1 Have these drugs and resuscitative equipment immediately available during denileukin diftitox therapy.1

General Precautions

Perform CBCs, blood chemistries, and renal and hepatic function tests prior to initiation of therapy and at weekly intervals during therapy.1 8

Possible development of antibodies to denileukin diftitox; may inhibit functional activity of denileukin diftitox.1

Systemic exposure to denileukin diftitox also may be decreased.1 3 (See Special Populations under Pharmacokinetics.)

Manufacturer states that presence or absence of antibodies does not correlate with the risk of immediate hypersensitivity reactions associated with IV infusion of the drug.1

May impair immune function; monitor carefully for development of possibly severe infections.1 3

Patients with CTCL may be predisposed to cutaneous infection.1

Possible moderate to severe hypoalbuminemia, usually occurring 1 or 2 weeks after administration of denileukin diftitox.1

Monitor serum albumin concentrations prior to initiating each course of therapy.1 Delay administration of the drug until serum albumin concentrations are at least 3 g/dL.1

Flu-like syndrome (e.g., fever and/or chills, asthenia, GI effects, myalgia, arthralgia) frequently reported within several hours to days after denileukin diftitox infusion.1 3 8

Mild to moderate symptoms generally responsive to antipyretics, antiemetics, or antidiarrhea agents.1 3

Specific Populations

Category C.1

Not known whether denileukin diftitox is distributed into milk.1 Discontinue nursing because of potential risk to nursing infants.1

Safety and efficacy not established.1

No substantial differences in efficacy relative to younger adults.1

Higher incidence and greater severity of anorexia, hypotension, anemia, confusion, rash, nausea, and/or vomiting observed in patients ≥65 years of age than in younger adults.1

Common Adverse Effects

Hypoalbuminemia, chills/fever, asthenia, infection, chest pain, hypotension, vasodilation, edema, dyspnea, nausea/vomiting, anorexia, diarrhea, anemia, increase in serum aminotransferase concentrations, dizziness, pain, headache, cough, rash, pruritus.1 3 4

Distribution

Extent

Distributed into liver and kidneys in rats.1

Elimination

Metabolism

Metabolized by proteolytic degradation.1

Half-life

Biphasic; terminal half-life is approximately 70–80 minutes.1

Special Populations

In patients with denileukin diftitox antibodies, clearance may be increased twofold to threefold.1 3

Ontak is supplied as 150 mcg/ml, sterile, frozen solution (300 mcg in 2 mL) in a sterile single-use vial.
NDC 62856-603-01, 6 vials in a package.

Store frozen at or below -10°C (14°F).

Applies to denileukin diftitox: intravenous solution

Other

Very common (10% or more): Infusion reactions (up to 70.5%), pyrexia (up to 63.6%), rigors (up to 47.3%), fatigue (up to 46.7%), peripheral edema (up to 25.5%), asthenia (up to 18.2%), pain (up to 12.7%), chest pain (up to 12.7%)[Ref]

Cardiovascular

Very common (10% or more): Capillary leak syndrome (up to 32.5%), hypotension (up to 16.4%)[Ref]

Ocular

Common (1% to 10%): Visual changes (e.g., visual acuity loss)[Ref]

Dermatologic

Very common (10% or more): Rash (up to 24.4%), pruritus (up to 18.2%)[Ref]

Endocrine

Postmarketing reports: Thyroid conditions (hyperthyroidism, thyroiditis, thyrotoxicosis, and hypothyroidism)

Gastrointestinal

Very common (10% or more): Nausea (up to 60%), vomiting (up to 34.5%), diarrhea (up to 22.2%)[Ref]

Hepatic

Very common (10% or more): Increased ALT or increased AST (up to 84%)[Ref]

Metabolic

Very common (10% or more): Anorexia (up to 20%)[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (up to 20%), back pain (up to 18.2%), arthralgia (up to 15.6%)[Ref]

Nervous system

Very common (10% or more): Headache (up to 28.9%), dizziness (up to 12.7%), dysgeusia (up to 10.9%)[Ref]

Respiratory

Very common (10% or more): Cough (up to 20%), upper respiratory tract infection (up to 13.3%), dyspnea (up to 13.3%)[Ref]

Some side effects of Ontak may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.