DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Proleukin (Aldesleukin) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The rate of drug-related deaths in the 255 metastatic RCC patients who received single-agent PROLEUKIN® (aldesleukin) was 4% (11/255); the rate of drug-related deaths in the 270 metastatic melanoma patients who received single-agent PROLEUKIN was 2% (6/270).

The following data on common adverse events (reported in greater than 10% of patients, any grade), presented by body system, decreasing frequency and by preferred term (COSTART) are based on 525 patients (255 with renal cell cancer and 270 with metastatic melanoma) treated with the recommended infusion dosing regimen.

TABLE III: ADVERSE EVENTS OCCURRING IN >/=10% OF PATIENTS (n=525)
Body System % Patients Body System % Patients
Body as a Whole Metabolic and Nutritional Disorders
   Chills 52    Bilirubinemia 40
   Fever 29    Creatinine increase 33
   Malaise 27    Peripheral edema 28
   Asthenia 23    SGOT increase 23
   Infection 13    Weight gain 16
   Pain 12    Edema 15
   Abdominal pain 11    Acidosis 12
   Abdomen enlarged 10    Hypomagnesium 12
Cardiovascular    Hypocalcemia 11
   Hypotension 71    Alkaline phosphatase increase 10
   Tachycardia 23 Nervous
   Vasodilation 13    Confusion 34
   Supraventricular tachycardia 12    Somnolence 22
   Cardiovascular disorder a 11    Anxiety 12
   Arrhythmia 10    Dizziness 11
Digestive Respiratory
   Diarrhea 67    Dyspnea 43
   Vomiting 50    Lung disorder b 24
   Nausea 35    Respiratory disorder c 11
   Stomatitis 22    Cough increase 11
   Anorexia 20    Rhinitis 10
   Nausea and vomiting 19 Skin and Appendages
Hemic and Lymphatic    Rash 42
   Thrombocytopenia 37    Pruritus 24
   Anemia 29    Exfoliative dermatitis 18
   Leukopenia 16 Urogenital
   Oliguria 63
a Cardiovascular disorder: fluctuations in blood pressure, asymptomatic ECG changes, CHF.
b Lung disorder: physical findings associated with pulmonary congestion, rales, rhonchi.
c Respiratory disorder: ARDS, CXR infiltrates, unspecified pulmonary changes.

The following data on life-threatening adverse events (reported in greater than 1% of patients, grade 4), presented by body system, and by preferred term (COSTART) are based on 525 patients (255 with renal cell cancer and 270 with metastatic melanoma) treated with the recommended infusion dosing regimen.

TABLE IV: LIFE-THREATENING (GRADE 4) ADVERSE EVENTS (n=525)
Body System # (%)
Patients
Body System # (%)
Patients
Body as a Whole Metabolic and Nutritional Disorders
   Fever 5 (1%)    Bilirubinemia 13 (2%)
   Infection 7 (1%)    Creatinine increase 5 (1%)
   Sepsis 6 (1%)    SGOT increase 3 (1%)
Cardiovascular    Acidosis 4 (1%)
   Hypotension 15 (3%) Nervous
   Supraventricular tachycardia 3 (1%)    Confusion 5 (1%)
   Cardiovascular disorder a 7 (1%)    Stupor 3 (1%)
   Myocardial infarct 7 (1%)    Coma 8 (2%)
   Ventricular tachycardia 5 (1%)    Psychosis 7 (1%)
   Heart arrest 4 (1%) Respiratory
Digestive    Dyspnea 5 (1%)
   Diarrhea 10 (2%)    Respiratory disorder c 14 (3%)
   Vomiting 7 (1%)    Apnea 5 (1%)
Hemic and Lymphatic Urogenital
   Thrombocytopenia 5 (1%)    Oliguria 33 (6%)
   Coagulation disorder b 4 (1%)    Anuria 25 (5%)
   Acute kidney failure 3 (1%)
a Cardiovascular disorder: fluctuations in blood pressure.
b Coagulation disorder: intravascular coagulopathy.
c Respiratory disorder: ARDS, respiratory failure, intubation.

The following life-threatening (grade 4) events were reported by <1% of the 525 patients: hypothermia; shock; bradycardia; ventricular extrasystoles; myocardial ischemia; syncope; hemorrhage; atrial arrhythmia; phlebitis; AV block second degree; endocarditis; pericardial effusion; peripheral gangrene; thrombosis; coronary artery disorder; stomatitis; nausea and vomiting; liver function tests abnormal; gastrointestinal hemorrhage; hematemesis; bloody diarrhea; gastrointestinal disorder; intestinal perforation; pancreatitis; anemia; leukopenia; leukocytosis; hypocalcemia; alkaline phosphatase increase; BUN increase; hyperuricemia; NPN increase; respiratory acidosis; somnolence; agitation; neuropathy; paranoid reaction; convulsion; grand mal convulsion; delirium; asthma, lung edema; hyperventilation; hypoxia; hemoptysis; hypoventilation; pneumothorax; mydriasis; pupillary disorder; kidney function abnormal; kidney failure; acute tubular necrosis.

In an additional population of greater than 1,800 patients treated with PROLEUKIN-based regimens using a variety of doses and schedules (e.g., subcutaneous, continuous infusion, administration with LAK cells) the following serious adverse events were reported: duodenal ulceration; bowel necrosis; myocarditis; supraventricular tachycardia; permanent or transient blindness secondary to optic neuritis; transient ischemic attacks; meningitis; cerebral edema; pericarditis; allergic interstitial nephritis; tracheo-esophageal fistula.

In the same clinical population, the following fatal events each occurred with a frequency of <1%: malignant hyperthermia; cardiac arrest; myocardial infarction; pulmonary emboli; stroke; intestinal perforation; liver or renal failure; severe depression leading to suicide; pulmonary edema; respiratory arrest; respiratory failure.

In patients with both metastatic RCC and metastatic melanoma, those with ECOG PS of 1 or higher had a higher treatment-related mortality, and serious adverse events.

Most adverse reactions are self-limiting and, usually, but not invariably, reverse or improve within 2 or 3 days of discontinuation of therapy. Examples of adverse reactions with permanent sequelae include: myocardial infarction, bowel perforation/infarction, and gangrene.

In post marketing experience, the following serious adverse events have been reported in a variety of treatment regimens that include interleukin-2: anaphylaxis; cellulitis; injection site necrosis; retroperitoneal hemorrhage; cardiomyopathy; cerebral hemorrhage; fatal endocarditis; hypertension; cholecystitis; colitis; gastritis; hepatitis; hepatosplenomegaly; intestinal obstruction; hyperthyroidism, neutropenia; myopathy; myositis; rhabdomyolysis; cerebral lesions; encephalopathy; extrapyramidal syndrome; insomnia; neuralgia; neuritis; neuropathy (demyelination); urticaria; pneumonia (bacterial, fungal, viral).

Exacerbation or initial presentation of a number of autoimmune and inflammatory disorders have been reported (See " WARNINGS " section, " PRECAUTIONS " section, " Drug Interactions " subsection). Persistent but nonprogressive vitiligo has been observed in malignant melanoma patients treated with interleukin-2. Synergistic, additive and novel toxicities have been reported with PROLEUKIN used in combination with other drugs. Novel toxicities include delayed adverse reactions to iodinated contrast media and hypersensitivity reactions to antineoplastic agents (See " PRECAUTIONS " section, " Drug Interactions " subsection).

Experience has shown the following concomitant medications to be useful in the management of patients on PROLEUKIN therapy: a) standard antipyretic therapy, including nonsteroidal anti-inflammatories (NSAIDs), started immediately prior to PROLEUKIN to reduce fever. Renal function should be monitored as some NSAIDs may cause synergistic nephrotoxicity; b) meperidine used to control the rigors associated with fever; c) H2 antagonists given for prophylaxis of gastrointestinal irritation and bleeding; d) antiemetics and antidiarrheals used as needed to treat other gastrointestinal side effects. Generally these medications were discontinued 12 hours after the last dose of PROLEUKIN.

Patients with indwelling central lines have a higher risk of infection with gram positive organisms. 9-11 A reduced incidence of staphylococcal infections in PROLEUKIN studies has been associated with the use of antibiotic prophylaxis which includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Hydroxyzine or diphenhydramine has been used to control symptoms from pruritic rashes and continued until resolution of pruritus. Topical creams and ointments should be applied as needed for skin manifestations. Preparations containing a steroid (e.g., hydrocortisone) should be avoided. NOTE:  Prior to the use of any product mentioned, the physician should refer to the package insert for the respective product.



REPORTS OF SUSPECTED PROLEUKIN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Proleukin. The information is not vetted and should not be considered as verified clinical evidence.

Possible Proleukin side effects / adverse reactions in 48 year old male

Reported by a pharmacist from United States on 2011-10-05

Patient: 48 year old male weighing 110.0 kg (242.0 pounds)

Reactions: Metastatic Malignant Melanoma, Cardio-Respiratory Arrest, Drug Intolerance, Neoplasm Progression

Adverse event resulted in: death

Suspect drug(s):
Proleukin



Possible Proleukin side effects / adverse reactions in 59 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-11

Patient: 59 year old male

Reactions: Blood Osmolarity Decreased, Blood Potassium Decreased, Urine Osmolarity Increased, Tachycardia, Hypotension, Inappropriate Antidiuretic Hormone Secretion, Hyponatraemia

Suspect drug(s):
Proleukin
    Indication: Metastases TO Liver

Proleukin
    Dosage: 600000 iu/kg, q8h
    Indication: Malignant Melanoma

Proleukin
    Indication: Metastases TO Lung

Other drugs received by patient: Sodium Chloride



Possible Proleukin side effects / adverse reactions in 59 year old male

Reported by a pharmacist from United States on 2011-10-18

Patient: 59 year old male

Reactions: Inappropriate Antidiuretic Hormone Secretion

Suspect drug(s):
Proleukin
    Dosage: 600000 iu/kg' q8h; iv
    Indication: Malignant Melanoma

Proleukin
    Dosage: 600000 iu/kg' q8h; iv
    Indication: Metastases TO Liver

Proleukin
    Dosage: 600000 iu/kg' q8h; iv
    Indication: Metastases TO Lung

Other drugs received by patient: Sodium Chloride



See index of all Proleukin side effect reports >>

Drug label data at the top of this Page last updated: 2006-10-10

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2014