Proleukin

Proleukin can cause serious side effects. See "Black Box Warning" and "Drug Precautions".

Common side effects of Proleukin are:

• nausea
• vomiting
• loss of appetite
• drowsiness
• weakness
• general feeling of being unwell (malaise)
• headache
• diarrhea
• dry skin

This is not a complete list of Proleukin side effects. Ask your doctor for more information.

Proleukin may make you drowsy. Do not drive a vehicle or operate machinery until you know how this medicine affects you.

Proleukin may lower blood cells required for your body to fight infection. Avoid people with known infection. Keep your hands away from your face and wash your hands often.

Proleukin may lower blood cells that are needed for blood clotting. Tell your doctor if you have unusual bruising, bleeding, or blood in stool.

Talk to your doctor before receiving any vaccination. Avoid vaccinations containing live viruses.

Do not take this medication if you are allergic to any of its active or inactive ingredients.

Do not take Proleukin if you have:

• hear arrhythmias (irregular rate or rhythm)
• chest pain or have had a heart attack
• kidney failure requiring dialysis (process of filtering your blood)
• had a coma or toxic psychosis
• seizures
• bowel ischemia (lack of oxygen to the intestines)
• bowel perforation (holes in the intestines)
• GI (stomach or intestinal) bleeding requiring surgery

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if Proleukin is excreted in human breast milk or if it will harm your nursing baby.

If Proleukin is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Keep all infusion and laboratory appointments. It is important to receive all scheduled Proleukin doses. Laboratory and medical test will be performed to monitor your response to the medicine.

Aldesleukin is injected into a vein through an IV. A healthcare provider will give you this injection.

Your breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be watched closely while you are receiving aldesleukin. Your blood will also need to be tested daily during treatment, and you may also need chest X-rays.

After 4 weeks off the medication, your doctor will examine you to determine if you need to be treated again with aldesleukin.

If you need to have any type of X-ray or CT scan using a dye that is injected into your veins, be sure the doctor knows ahead of time if you have recently received aldesleukin. Some people treated with aldesleukin or similar medication have had unusual allergic reactions to contrast agents used within weeks to several months later.

Call your doctor for instructions if you miss an appointment for your aldesleukin injection.

In the U.S.

• Proleukin

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Interleukin

Aldesleukin injection is anticancer medicine that is used to treat metastatic kidney cancer (cancer that has already spread to the body) and metastatic skin cancer.

Aldesleukin is a man-made version of a substance called interleukin-2. Interleukins are produced naturally by cells in the body to help white blood cells work.

Aldesleukin causes very serious side effects in addition to its helpful effects. Some effects can be fatal. For that reason, aldesleukin injection is given only in the hospital. If severe side effects occur, which is common, treatment in an intensive care unit (ICU) may be necessary. Other effects may not be serious but may cause concern. Before you begin treatment with aldesleukin, you and your doctor should talk about the benefits this medicine will do as well as the risks of using it.

This medicine is to be administered only by or under the immediate supervision of your doctor.

Medicines used to treat cancer are very strong and can have many side effects. Before receiving this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

You will receive this medicine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins.

• It is used to treat kidney cancer.
• It is used to treat a type of skin cancer (melanoma).
• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of thyroid problems like a change in weight without trying, feeling nervous and excitable, feeling restless, feeling very weak, hair thinning, low mood (depression), neck swelling, not able to focus, not able to handle heat or cold, period (menstrual) changes, shakiness, or sweating.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of gallbladder problems like pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or very upset stomach or throwing up.
• Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat the does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Very bad dizziness or passing out.
• Mouth irritation or mouth sores.
• Hallucinations (seeing or hearing things that are not there).
• Trouble speaking.
• Trouble walking.
• Change in balance.
• Loss of eyesight.
• Low mood (depression).
• Any unexplained bruising or bleeding.
• Any skin change.
• Feeling very tired or weak.
• Swelling.
• Shortness of breath.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Proleukin® (aldesleukin), a human recombinant interleukin-2 product, is a highly purified protein with a molecular weight of approximately 15,300 daltons. The chemical name is des-alanyl-1, serine-125 human interleukin-2. Proleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human interleukin-2. This recombinant form differs from native interleukin-2 in the following ways: a) Proleukin is not glycosylated because it is derived from E. coli ; b) the molecule has no N-terminal alanine; the codon for this amino acid was deleted during the genetic engineering procedure; c) the molecule has serine substituted for cysteine at amino acid position 125; this was accomplished by site specific manipulation during the genetic engineering procedure; and d) the aggregation state of Proleukin is likely to be different from that of native interleukin-2.

The in vitro biological activities of the native nonrecombinant molecule have been reproduced with Proleukin.1,2

Proleukin is supplied as a sterile, white to off-white, lyophilized cake in single-use vials intended for intravenous administration. When reconstituted with 1.2 mL Sterile Water for Injection, USP, each mL contains 18 million International Units (1.1 mg) Proleukin, 50 mg mannitol, and 0.18 mg sodium dodecyl sulfate, buffered with approximately 0.17 mg monobasic and 0.89 mg dibasic sodium phosphate to a pH of 7.5 (range 7.2 to 7.8). The manufacturing process for Proleukin involves fermentation in a defined medium containing tetracycline hydrochloride. The presence of the antibiotic is not detectable in the final product. Proleukin contains no preservatives in the final product.

Proleukin biological potency is determined by a lymphocyte proliferation bioassay and is expressed in International Units as established by the World Health Organization 1st International Standard for Interleukin-2 (human). The relationship between potency and protein mass is as follows:

18 million International Units Proleukin = 1.1 mg protein

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.

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.

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.

Immunogenicity

Serum samples from patients in the clinical studies were tested by enzyme-linked immunosorbent assay (ELISA) for anti-aldesleukin antibodies. Low titers of anti-aldesleukin antibodies were detected in 57 of 77 (74%) patients with metastatic renal cell carcinoma treated with an every 8-hour Proleukin regimen and in 33 of 50 (66%) patients with metastatic melanoma treated with a variety of intravenous regimens. In a separate study, the effect of immunogenicity on the pharmacokinetics of aldesleukin was evaluated in 13 patients. Following the first cycle of therapy, comparing the geometric mean aldesleukin exposure (AUC) Day 15 to Day 1, there was an average 68% increase in 11 patients who developed anti-aldesleukin antibodies and no change was observed in the antibody-negative patients (n=2). Overall, neutralizing antibodies were detected in 1 patient. The impact of antialdesleukin antibody formation on clinical efficacy and safety of Proleukin is unknown.

Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Proleukin with the incidence of antibodies to other products may be misleading.

Post Marketing Experience

The following adverse reactions have been identified during post-approval use of Proleukin.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Blood and lymphatic system: neutropenia, febrile neutropenia, eosinophilia, lymphocytopenia
• Cardiac: cardiomyopathy, cardiac tamponade
• Endocrine: hyperthyroidism
• Gastrointestinal: gastritis, intestinal obstruction, colitis
• General and administration site conditions: injection site necrosis
• Hepatobiliary: hepatitis, hepatosplenomegaly, cholecystitis
• Immune system: anaphylaxis, angioedema, urticaria
• Infections and infestations: pneumonia (bacterial, fungal, viral), fatal endocarditis, cellulitis
• Musculoskeletal and connective tissue: myopathy, myositis, rhabdomyolysis
• Nervous system: cerebral lesions, encephalopathy, extrapyramidal syndrome, neuralgia, neuritis, demyelinating neuropathy
• Psychiatric: insomnia
• Vascular: hypertension, fatal subdural and subarachnoid hemorrhage, cerebral hemorrhage, retroperitoneal hemorrhage

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.

Side effects following the use of Proleukin® (aldesleukin) appear to be dose-related. Exceeding the recommended dose has been associated with a more rapid onset of expected dose-limiting toxicities. Symptoms which persist after cessation of Proleukin should be monitored and treated supportively. Life-threatening toxicities may be ameliorated by the intravenous administration of dexamethasone, which may also result in loss of the therapeutic effects of Proleukin.12 NOTE: Prior to the use of dexamethasone, the physician should refer to the package insert for this product.

The recommended Proleukin® (aldesleukin) treatment regimen is administered by a 15-minute intravenous infusion every 8 hours. Before initiating treatment, carefully review the “INDICATIONS AND USAGE”, “CONTRAINDICATIONS”, “WARNINGS”, “PRECAUTIONS”, and “ADVERSE REACTIONS” sections, particularly regarding patient selection, possible serious adverse events, patient monitoring and withholding dosage. The following schedule has been used to treat adult patients with metastatic renal cell carcinoma (metastatic RCC) or metastatic melanoma. Each course of treatment consists of two 5-day treatment cycles separated by a rest period.

600,000 International Units/kg (0.037 mg/kg) dose administered every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Following 9 days of rest, the schedule is repeated for another 14 doses, for a maximum of 28 doses per course, as tolerated. During clinical trials, doses were frequently withheld for toxicity (See “CLINICAL STUDIES” section and “Dose Modifications” subsection). Metastatic RCC patients treated with this schedule received a median of 20 of the 28 doses during the first course of therapy. Metastatic melanoma patients received a median of 18 doses during the first course of therapy.

Retreatment

Patients should be evaluated for response approximately 4 weeks after completion of a course of therapy and again immediately prior to the scheduled start of the next treatment course. Additional courses of treatment should be given to patients only if there is some tumor shrinkage following the last course and retreatment is not contraindicated (See “CONTRAINDICATIONS” section). Each treatment course should be separated by a rest period of at least 7 weeks from the date of hospital discharge.

Dose Modifications

Dose modification for toxicity should be accomplished by withholding or interrupting a dose rather than reducing the dose to be given. Decisions to stop, hold, or restart Proleukin therapy must be made after a global assessment of the patient. With this in mind, the following guidelines should be used:

Retreatment with Proleukin is contraindicated in patients who have experienced the following toxicities:

Doses should be held and restarted according to the following:

* Discontinue all further treatment for that course. A new course of treatment, if warranted, should be initiated no sooner than 7 weeks after cessation of adverse event and hospital discharge.

Reconstitution and Dilution Directions: Reconstitution and dilution procedures other than those recommended may alter the delivery and/or pharmacology of Proleukin and thus should be avoided.

1. Proleukin® (aldesleukin) is a sterile, white to off-white, preservative-free, lyophilized powder suitable for IV infusion upon reconstitution and dilution. EACH VIAL CONTAINS 22 MILLION International Units (1.3 mg) OF Proleukin AND SHOULD BE RECONSTITUTED ASEPTICALLY WITH 1.2 mL OF STERILE WATER FOR INJECTION, USP. WHEN RECONSTITUTED AS DIRECTED, EACH mL CONTAINS 18 MILLION International Units (1.1 mg) OF Proleukin. The resulting solution should be a clear, colorless to slightly yellow liquid. The vial is for single-use only and any unused portion should be discarded.
   
2. During reconstitution, the Sterile Water for Injection, USP should be directed at the side of the vial and the contents gently swirled to avoid excess foaming. DO NOT SHAKE.
   
3. The dose of Proleukin, reconstituted with Sterile Water for Injection, USP (without preservative) should be diluted aseptically in 50 mL of 5% Dextrose Injection, USP (D5W) and infused over a 15-minute period.
   
   In cases where the total dose of Proleukin is 1.5 mg or less (e.g., a patient with a body weight of less than 40 kilograms), the dose of Proleukin should be diluted in a smaller volume of D5W. Concentrations of Proleukin below 0.03 mg/mL and above 0.07 mg/mL have shown increased variability in drug delivery. Dilution and delivery of Proleukin outside of this concentration range should be avoided.
   
4. Glass bottles and plastic (polyvinyl chloride) bags have been used in clinical trials with comparable results. It is recommended that plastic bags be used as the dilution container since experimental studies suggest that use of plastic containers results in more consistent drug delivery. In-line filters should not be used when administering Proleukin.
   
5. Before and after reconstitution and dilution, store in a refrigerator at 2° to 8°C (36° to 46°F). Do not freeze. Administer Proleukin within 48 hours of reconstitution. The solution should be brought to room temperature prior to infusion in the patient.
   
6. Reconstitution or dilution with Bacteriostatic Water for Injection, USP, or 0.9% Sodium Chloride Injection, USP should be avoided because of increased aggregation. Proleukin should not be coadministered with other drugs in the same container.
   
7. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Applies to aldesleukin: intravenous powder for solution

Along with its needed effects, aldesleukin (the active ingredient contained in Proleukin) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking aldesleukin:

• Agitation
• confusion
• diarrhea
• dizziness
• drowsiness
• fever or chills
• mental depression
• nausea and vomiting
• shortness of breath
• sores in the mouth and on lips
• tingling of the hands or feet
• unusual decrease in urination
• unusual tiredness or weakness
• weight gain of 5 to 10 pounds or more

• Bloating and stomach pain
• blurred or double vision
• faintness
• fast or irregular heartbeat
• loss of taste
• rapid breathing
• redness, swelling, and soreness of the tongue
• trouble with speaking
• yellow eyes and skin

• Changes in menstrual periods
• clumsiness
• coldness
• convulsions (seizures)
• listlessness
• muscle aches
• pain or redness at injection site
• sudden inability to move
• swelling in the front of the neck
• swelling of the feet or lower legs
• weakness

• Black, tarry stools
• blisters on the skin
• blood in the urine
• bloody vomit
• chest pain
• cough or hoarseness
• lower back or side pain
• painful or difficult urination
• pinpoint red spots on the skin
• stomach pain (severe)
• unusual bleeding or bruising

Some side effects of aldesleukin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dry skin
• loss of appetite
• skin rash or redness with burning or itching, followed by peeling
• unusual feeling of discomfort or illness

• Constipation
• headache
• joint pain
• muscle pain

Applies to aldesleukin: intravenous powder for injection

Immunologic

-Very common (10% or more): Anti-aldesleukin (the active ingredient contained in Proleukin) antibodies (up to 74%)
-Common (1% to 10%): Neutralizing antibodies[Ref]

Cardiovascular

-Very common (10% or more): Hypotension (up to 71%), tachycardia (up to 23%), vasodilation (up to 13%), supraventricular tachycardia (up to 12%), cardiovascular disorder (up to 11%), arrhythmia (up to 10%), chest pain
-Common (1% to 10%): Myocardial infarction, ventricular tachycardia, cardiac arrest, cyanosis, transient ECG changes, myocardial ischemia, palpitations, phlebitis, hypertension
-Uncommon (0.1% to 1%): Hemorrhage (including subdural, subarachnoid, cerebral, retroperitoneal), myocarditis, cardiomyopathy, pericardial effusion, thrombosis, thrombophlebitis
-Rare (less than 0.1%): Ventricular hypokinesia
-Frequency not reported: Capillary leak syndrome, hypoperfusion, bradycardia, ventricular extrasystoles, atrial arrhythmia, second degree AV block, endocarditis, coronary artery disorder, transient ischemic attacks, pericarditis, shock
-Postmarketing reports: Cardiac tamponade[Ref]

Cardiovascular disorder includes fluctuations in blood pressure, asymptomatic ECG changes, cardiac failure, and congestive heart failure.[Ref]

Gastrointestinal

-Very common (10% or more): Diarrhea (up to 67%), vomiting (up to 50%), nausea (up to 35%), stomatitis (up to 22%), nausea with vomiting (up to 19%), abdominal pain (up to 11%), enlarged abdomen (up to 10%)
-Common (1% to 10%): Dysphagia, dyspepsia, constipation, GI bleeding (including rectal hemorrhage), hematemesis, ascites, cheilitis, gastritis
-Uncommon (0.1% to 1%): Pancreatitis, intestinal obstruction, GI perforation (including necrosis/gangrene)
-Rare (less than 0.1%): Activation of quiescent Crohn's disease
-Frequency not reported: GI hemorrhage, bloody diarrhea, GI disorder, intestinal perforation, duodenal ulceration, bowel necrosis, bowel perforation/infarction
-Postmarketing reports: Colitis[Ref]

Renal

-Very common (10% or more): Oliguria (up to 63%), increased serum creatinine (up to 33%), increased serum urea
-Common (1% to 10%): Anuria, hematuria, renal failure
-Frequency not reported: Increased blood urea nitrogen, crescentic IgA glomerulonephritis, acute tubular necrosis, allergic interstitial nephritis
-Postmarketing reports: Increased hyperuricemia non-protein nitrogen[Ref]

Other

-Very common (10% or more): Chills (up to 52%), fever (up to 29%), peripheral edema (up to 28%), malaise (up to 27%), asthenia/fatigue (up to 23%), edema (up to 15%), infection (up to 13%), pain (up to 12%), injection site reactions, injection site necrosis, injection site pain, injection site inflammation
-Common (1% to 10%): Sepsis, mucositis, injection site nodule, hypothermia
-Frequency not reported: Peripheral gangrene, atypical reactions to iodinated contrast media, catheter site infections, bacterial infections, malignant hyperthermia[Ref]

Respiratory

Lung disorder includes physical findings associated with pulmonary congestion, rales, and rhonchi. Respiratory disorder includes acute respiratory distress syndrome (ARDS), chest x-ray infiltrates, respiratory failure, intubation, and unspecified pulmonary changes.[Ref]

-Very common (10% or more): Dyspnea (up to 43%), lung disorder (up to 24%), respiratory disorder (up to 11%), increased cough (up to 11%), rhinitis (up to 10%)
-Common (1% to 10%): Apnea, respiratory tract infection, lung/pulmonary edema, pleural effusion, hypoxia, hemoptysis, epistaxis, nasal congestion, rhinitis
-Rare (less than 0.1%): Pulmonary embolism
-Frequency not reported: Respiratory acidosis, asthma, hyperventilation, hypoventilation, pneumothorax, trachea-esophageal fistula, respiratory arrest
-Postmarketing reports: Pneumonia (bacterial, fungal, viral)[Ref]

Dermatologic

-Very common (10% or more): Erythema and rash (up to 42%), pruritus (up to 24%), exfoliative dermatitis (up to 18%), sweating
-Common (1% to 10%): Urticaria, alopecia
-Uncommon (0.1% to 1%): Quincke's edema, vitiligo
-Rare (less than 0.1%): Vesiculobullous rash, Stevens-Johnson syndrome
-Frequency not reported: Bullous pemphigoid, cutaneous and leukocytoplastic hypersensitivity vasculitis
-Postmarketing reports: Cellulitis[Ref]

Hepatic

-Very common (10% or more): Bilirubinemia (up to 40%), increased SGOT (up to 23%)
-Common (1% to 10%): Acute kidney failure, elevation of hepatic transaminases
-Uncommon (0.1% to 1%): Hyperbilirubinemia, hepatomegaly/hepatosplenomegaly
-Rare (less than 0.1%): Cholecystitis, liver failure
-Frequency not reported: Abnormal liver function tests, abnormal kidney function
-Postmarketing reports: Hepatitis[Ref]

Hematologic

-Very common (10% or more): Thrombocytopenia (up to 37%), anemia (up to 29%), leukopenia (up to 16%)
-Common (1% to 10%): Coagulopathy (including disseminated intravascular coagulation), eosinophilia
-Uncommon (0.1% to 1%): Neutropenia
-Rare (less than 0.1%): Agranulocytosis, aplastic anemia, hemolytic anemia, neutropenic fever
-Frequency not reported: Leukocytosis, lymphocytosis
-Postmarketing reports: Lymphocytopenia[Ref]

Psychiatric

-Very common (10% or more): Confusion (up to 34%), anxiety (up to 12%), depression, insomnia
-Common (1% to 10%): Psychosis, irritability, agitation, hallucinations
-Frequency not reported: Paranoid reaction, delirium, suicide[Ref]

Endocrine

-Very common (10% or more): Hypothyroidism
-Common (1% to 10%): Hyperthyroidism, hyperglycemia
-Uncommon (0.1% to 1%): Hypoglycemia
-Rare (less than 0.1%): Diabetes mellitus
-Frequency not reported: Thyroiditis[Ref]

Metabolic

-Very common (10% or more): Anorexia (up to 20%), weight gain (up to 16%), acidosis (up to 12%), hypomagnesemia (up to 12%), hypocalcemia (up to 11%), increased alkaline phosphatase (up to 10%), weight loss
-Common (1% to 10%): Hypercalcemia, hyperkalemia, dehydration, elevated lactic dehydrogenase[Ref]

Nervous system

-Very common (10% or more): Somnolence (up to 22%), dizziness (up to 11%), headache, paraesthesia
-Common (1% to 10%): Coma, stupor, neuropathy, syncope, speech disorders, taste loss, lethargy
-Uncommon (0.1% to 1%): Convulsions, paralysis
-Rare (less than 0.1%): Leukoencephalopathy
-Frequency not reported: Grand mal convulsion, meningitis, cerebral edema, mental status changes, ataxia (limb or gait), cortical lesion, cerebral vasculitis, obtundation, cerebrovascular accident, stroke, cerebral vasculitis
-Postmarketing reports: Cerebral lesions, extrapyramidal syndrome, neuralgia, neuritis, demyelinating neuropathy[Ref]

General

Most adverse reactions were self-limited and usually reversed or improved within 1 to 3 days of therapy cessation. However, some adverse reactions (e.g., myocardial infarction, bowl perforation/infarction, gangrene) have permanent sequelae.[Ref]

Hypersensitivity

-Uncommon (0.1% to 1%): Hypersensitivity reactions
-Rare (less than 0.1%): Anaphylaxis[Ref]

Musculoskeletal

-Common (1% to 10%): Myalgia, arthralgia
-Uncommon (0.1% to 1%): Myasthenia, myopathy, myositis
-Frequency not reported: Scleroderma, inflammatory arthritis, oculobulbar myasthenia gravis
-Postmarketing reports: Rhabdomyolysis[Ref]

Ocular

-Common (1% to 10%): Conjunctivitis
-Rare (less than 0.1%): Optic nerve disorder (including optic neuritis)
-Frequency not reported: Cortical blindness, mydriasis, pupillary disorder, blindness (permanent and transient)[Ref]

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