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Denileukin diftitox Side Effects

Not all side effects for denileukin diftitox may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to denileukin diftitox: intravenous injectable, intravenous solution

In addition to its needed effects, some unwanted effects may be caused by denileukin diftitox. In the event that any of these side effects do occur, they may require medical attention.

If any of the following side effects occur while taking denileukin diftitox, check with your doctor or nurse immediately:

More common
  • Back pain
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blurred vision
  • body aches or pain
  • chest pain
  • confusion
  • cough
  • difficulty with breathing
  • difficulty with moving
  • difficulty with swallowing
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • ear congestion
  • fast or irregular heartbeat
  • feeling unusually cold
  • fever or chills
  • headache
  • loss of appetite
  • loss of strength or energy
  • loss of voice
  • muscle aching or cramping
  • muscle pains or stiffness
  • nasal congestion
  • nausea
  • pain in the joints and muscles
  • rapid weight gain
  • rash
  • runny nose
  • shivering
  • shortness of breath
  • sneezing
  • sore throat
  • sweating
  • swollen joints
  • tightness in the chest
  • tingling of the hands or feet
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
  • warmth and flushing of the skin
  • wheezing
Less common
  • Abdominal pain, severe
  • black, tarry stools
  • blood in the urine or stools
  • cloudy urine
  • cough or hoarseness accompanied by fever or chills
  • headache, severe
  • loss of coordination
  • lower back or side pain accompanied by fever or chills
  • pain in the groin or leg
  • painful or difficult urination accompanied by fever or chills
  • pinpoint red spots on the skin
  • slurring of speech
  • sudden vision changes
  • swelling or pain at the injection site
  • unusual bleeding or bruising
  • weakness of the arm and leg
  • Dry, puffy skin
  • increased heart rate
  • weight gain

Some of the side effects that can occur with denileukin diftitox may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Change in taste
  • diarrhea
  • itching
  • loss of taste
Less common
  • Constipation
  • indigestion
  • numbness or tingling of the fingers, toes, or face
  • runny nose
  • trouble with sleeping

For Healthcare Professionals

Applies to denileukin diftitox: intravenous solution


Cardiovascular side effects including hypotension (36%), vasodilation (22%), tachycardia (12%), thrombotic events (7%), hypertension (6%), and arrhythmia (6%) have been reported.[Ref]

Two patients with preexisting coronary artery disease experienced acute myocardial infarctions while receiving denileukin diftitox. In addition, ten patients (7%) experienced thrombotic events. Six other patients experienced less severe superficial thrombophlebitis.[Ref]


Gastrointestinal side effects including nausea/vomiting (64%), anorexia (up to 36%), diarrhea (up to 29%), constipation (9%), dyspepsia (7%), and dysphagia (6%) have been reported.[Ref]

Onset of diarrhea may be delayed and the duration may be prolonged after taking denileukin diftitox. Dehydration, occurring with vomiting or anorexia, has been reported in 9% of patients.[Ref]


Hematologic side effects including anemia (18%), thrombocytopenia (8%), and leukopenia (6%) have been the major hematologic adverse effects reported in patients receiving denileukin diftitox.[Ref]


Musculoskeletal side effects including myalgias (up to 20%) and arthralgias (up to 15.6%) have been reported.[Ref]

Nervous system

Nervous system side effects have included dizziness (22%), paresthesia (13%), nervousness (11%), confusion (8%), and insomnia (9%).[Ref]


Respiratory side effects have included dyspnea (up to 29%), increased cough (up to 26%), pharyngitis (17%), upper respiratory tract infection (13.3%), rhinitis (13%), and lung disorder (8%).[Ref]


Various rashes have been reported including maculopapular, petechial, vesicular bullous, urticaria with or without eczematous with both an acute and delayed onset. Treatment of the minor rashes includes antihistamines, and, for more severe rashes, topical and/or oral steroids may be required.[Ref]

Dermatologic side effects including rash (up to 34%), pruritus (up to 20%), and sweating (10%) have been reported.[Ref]


Genitourinary side effects including hematuria (10%), albuminuria (10%), pyuria (10%), and increased creatinine (7%) have been reported.[Ref]


The flu-like syndrome has been reported in 91% of patients several hours to days after infusion of denileukin diftitox. Symptoms consisted of the following, fever, and/or chills (81%), asthenia (66%), digestive (64%), myalgias (18%), and arthralgias (8%). These symptoms were mild to moderate in the majority of patients and responded to treatment with antipyretics and/or antiemetics.[Ref]

General side effects have included chills/fever (81%), asthenia (up to 66%), pyrexia (63.6%), infection (48%), pain (up to 48%), rigors (47.3%), fatigue (46.7%), headache (up to 28.9%), peripheral edema (25.5%), chest pain (up to 24%), flu-like syndrome (8%).[Ref]


Hypersensitivity side effects including acute hypersensitivity reactions have been reported in 69% of patients during or within 24 hours of infusion with denileukin diftitox.[Ref]

Symptoms associated with the hypersensitivity reaction include, hypotension in 50%, back pain in 30%, dyspnea in 28%, vasodilation in 28%, rash in 25%, chest pain/tightness in 24%, tachycardia in 12%, dysphagia in 5%, syncope in 3% and/or anaphylaxis in 1% of reported patients. Management of this condition consists of decrease or discontinuation of the denileukin diftitox infusion and administration of IV antihistamines, corticosteroids and/or epinephrine.[Ref]


Hypoalbuminemia has been reported in 83% of patients receiving denileukin diftitox and has been considered moderate to severe in 17% of patients. In the majority of patients, the nadir was seen 1 to 2 weeks after drug administration. The manufacturer recommends monitoring albumin levels before each course of denileukin diftitox and delaying treatment until levels are at least 3 g/dL.[Ref]

Metabolic side effects reported in patients receiving denileukin diftitox have included hypoalbuminemia (83%), increased transaminases (61%), edema (47%), hypocalcemia (17%), decreased weight (14%), dehydration (9%), and hypokalemia (6%).[Ref]


The vascular leak syndrome was delayed and occurred within the first two weeks of therapy. Symptoms included hypotension, edema and/or hypoalbuminemia. Careful monitoring of weight, edema, blood pressure and albumin levels is recommended with treatment dependent on whether edema or hypotension is the primary problem.[Ref]

Other side effects have included vascular leak syndrome (27%) and dysgeusia (10.9%).[Ref]


Immunologic side effects have included various types of infections (48%) as well as decreased lymphocyte counts (34%).[Ref]

The lymphocyte count, generally, dropped during the dosing period and returned to normal by day 15. With subsequent courses, smaller changes with more rapid recoveries were seen.[Ref]


Ocular side effects including loss of visual acuity usually with loss of color vision with or without retinal pigment mottling has been reported.[Ref]

Recovery was reported in some of the affected patients. However, most patients reported persistent visual impairment.[Ref]


Hepatic side effects including an increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) from baseline has been reported in 84% of subjects treated with denileukin diftitox.[Ref]

In the majority of subjects, these enzyme elevations occurred during either the first or the second cycle. Enzyme elevation resolved without medical intervention and did not require discontinuation of denileukin diftitox.[Ref]


Local side effects including injection site reaction (8%) have been reported.


1. "Product Information. Ontak (denileukin diftitox)." Ligand Pharmaceuticals, San Diego, CA.

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