Aldesleukin

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe drowsiness, feeling like you might pass out;
• chest pain, fast or pounding heartbeats;
• runny or stuffy nose, cough, rapid breathing and heart rate, trouble breathing, swelling and pain in any part of your body;
• problems with vision, speech, balance, or coordination;
• mood or behavior changes, confusion, agitation, hallucinations;
• seizures (convulsions);
• swelling, rapid weight gain, little or no urinating;
• black, bloody, or tarry stools;
• a blistering skin rash;
• jaundice (yellowing of the skin or eyes); or
• signs of infection such as fever, chills, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), nausea and vomiting, mouth sores, unusual weakness.

Common side effects may include:

• mild stomach pain, diarrhea, loss of appetite.
• tired feeling; or
• drowsiness, dizziness, anxiety.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

GENERIC AVAILABLE: No

Aldesleukin may be found in some form under the following brand names:

• Proleukin

Before receiving aldesleukin tell your doctor about all of your medical conditions including if you:

• are allergic to aldesleukin
• have or have had heart, lung, brain, kidney, liver or autoimmune disease
• have an infection
• have epilepsy
• have high blood calcium levels (hypercalcemia)
• are pregnant or breastfeeding

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

If aldesleukin 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.

You should not receive this medication if you are allergic to aldesleukin or interleukin-2, or if you have:

• an infection caused by bacteria;

• if you have received an organ transplant;

• if you have recently had an abnormal lung function test; or

• if you have recently had an abnormal exercise test showing decreased blood flow to your heart.

You may not be able to receive aldesleukin if you have had any of these side effects while receiving aldesleukin in the past:

• irregular heart rhythm;

• chest pain;

• a build-up of fluid around your heart;

• kidney failure;

• seizures;

• psychosis (thinking problems, hallucinations, or changes in personality);

• stomach or intestinal bleeding; or

• if you needed a breathing tube.

To make sure you aldesleukin is safe for you, tell your doctor if you have:

• heart disease, angina (chest pain), a heart rhythm disorder, or history of heart attack;

• lung or breathing problems;

• kidney disease;

• liver disease;

• gallbladder disease;

• high levels of calcium in your blood (hypercalcemia);

• a thyroid disorder;

• diabetes;

• a seizure disorder;

• mental illness or neurologic problems; or

• an autoimmune disorder such as Crohn's disease, scleroderma, arthritis, myasthenia gravis, or a chronic skin disorder.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether aldesleukin passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

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.

Usual Adult Dose for Renal Cell Carcinoma:

0.037 mg/kg (600,000 IU/kg) every 8 hours via a 15-minute IV infusion for a maximum of 14 doses; the schedule is repeated for another 14 doses after 9 days of rest.

Maximum Dose: 28 doses per course, as tolerated

Therapy Duration: During the first therapy course, metastatic RCC patients received a median of 20 doses and metastatic melanoma patients received a median of 18 doses.

Comments:
-Each treatment course consists of two 5-day treatment cycles separated by a rest period.
-Patient selection should include assessment of ECOG PS (Eastern Cooperative Oncology Group performance status).

Use: Treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma.

Usual Adult Dose for Melanoma - Metastatic:

0.037 mg/kg (600,000 IU/kg) every 8 hours via a 15-minute IV infusion for a maximum of 14 doses; the schedule is repeated for another 14 doses after 9 days of rest.

Maximum Dose: 28 doses per course, as tolerated

Therapy Duration: During the first therapy course, metastatic RCC patients received a median of 20 doses and metastatic melanoma patients received a median of 18 doses.

Comments:
-Each treatment course consists of two 5-day treatment cycles separated by a rest period.
-Patient selection should include assessment of ECOG PS (Eastern Cooperative Oncology Group performance status).

Use: Treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma.

• Biologic response modifier; possesses biologic activities of IL-2.1

• Precise mechanism of action unknown; whether effects on immune system contribute to antineoplastic activity not established.1

• Exerts a wide range of regulatory actions on the immune system in vitro, including enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human IL-2 dependent cell lines, enhancement of lymphocyte cytotoxicity, induction of LAK cell and natural killer (NK) cell activity, and induction of interferon-gamma production.1

• Produces immune effects in a dose-dependent manner.1 Activates cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia; stimulates production of cytokines (e.g., tumor necrosis factor, IL-1, interferon gamma).1

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Upset stomach or throwing up.
• Anxiety.
• Not hungry.
• Loose stools (diarrhea).
• Runny nose.
• Feeling tired or weak.
• Feeling sleepy.
• Joint pain.
• Weight gain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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

Neuroblastoma, high-risk (pediatrics)

Data from a phase III study supports the use of aldesleukin (in combination with isotretinoin, dinutuximab [an anti-GD2 antibody], and sargramostim) in the treatment of high-risk neuroblastoma in pediatrics after response to induction therapy and stem cell transplantation [Yu 2010].

Adults:

Renal impairment prior to treatment initiation:

Serum creatinine ≤1.5 mg/dL: There are no dosage adjustments provided in the manufacturer’s labeling.

Serum creatinine >1.5 mg/dL: Do not initiate treatment.

Renal toxicity during treatment:

Serum creatinine >4.5 mg/dL (or ≥4 mg/dL with severe volume overload, acidosis, or hyperkalemia): Withhold dose; may resume when <4 mg/dL and fluid/electrolyte status is stable.

Persistent oliguria or urine output <10 mL/hour for 16 to 24 hours with rising serum creatinine: Withhold dose; may resume when urine output >10 mL/hour with serum creatinine decrease of >1.5 mg/dL or normalization.

Hemodialysis: Re-treatment is contraindicated in patients with renal failure requiring dialysis for >72 hours.

Reconstitute vials with 1.2 mL SWFI (preservative free) to a concentration of 18 million units (1.1 mg)/1 mL (sterile water should be injected towards the side of the vial). Gently swirl; do not shake. Further dilute with 50 mL of D5W. Smaller volumes of D5W should be used for doses ≤1.5 mg; avoid concentrations <30 mcg/mL and >70 mcg/mL (an increased variability in drug delivery has been seen). Plastic (polyvinyl chloride) bags result in more consistent drug delivery and are recommended. Filtration may result in loss of bioactivity. Addition of 0.1% albumin has been used to increase stability and decrease the extent of sorption if low final concentrations cannot be avoided.

Avoid bacteriostatic water for injection and NS for reconstitution or dilution; increased aggregation may occur.

>10%:

Cardiovascular: Hypotension (71%, grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilatation (13%), supraventricular tachycardia (12%, grade 4: 1%), cardiac disease (11%; includes blood pressure changes, HF and ECG changes)

Central nervous system: Chills (52%), confusion (34%, grade 4: 1%), malaise (27%), drowsiness (22%), anxiety (12%), pain (12%), dizziness (11%)

Dermatologic: Skin rash (42%), pruritus (24%), exfoliative dermatitis (18%)

Endocrine & metabolic: Weight gain (16%), acidosis (12%, grade 4: 1%), hypomagnesemia (12%), hypocalcemia (11%)

Gastrointestinal: Diarrhea (67%, grade 4: 2%), vomiting (19% to 50%, grade 4: 1%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), abdominal pain (11%)

Genitourinary: Oliguria (63%, grade 4: 6%)

Hematologic & oncologic: Thrombocytopenia (37%, grade 4: 1%), anemia (29%), leukopenia (16%)

Hepatic: Hyperbilirubinemia (40%, grade 4: 2%), increased serum AST (23%, grade 4: 1%)

Immunologic: Antibody development (66% to 74%)

Infection: Infection (13%, grade 4: 1%)

Miscellaneous: Fever (29%, grade 4: 1%)

Neuromuscular & skeletal: Weakness (23%)

Renal: Increased serum creatinine (33%, grade 4: 1%)

Respiratory: Dyspnea (43%, grade 4: 1%), pulmonary disease (24%; includes pulmonary congestion, rales, rhonchi), cough (11%), respiratory tract disease (11%; includes acute respiratory distress syndrome, pulmonary infiltrates, and pulmonary changes)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (10%), cardiac arrest (grade 4: 1%), myocardial infarction (grade 4: 1%), ventricular tachycardia (grade 4: 1%)

Central nervous system: Coma (grade 4: 2%), psychosis (grade 4: 1%), stupor (grade 4: 1%)

Gastrointestinal: Enlargement of abdomen (10%)

Genitourinary: Anuria (grade 4: 5%)

Hematologic & oncologic: Blood coagulation disorder (grade 4: 1%; includes intravascular coagulopathy)

Hepatic: Increased serum alkaline phosphatase (10%)

Infection: Sepsis (grade 4: 1%)

Renal: Acute renal failure (grade 4: 1%)

Respiratory: Rhinitis (10%), apnea (grade 4: 1%)

<1% (Limited to important or life-threatening): Agitation, allergic interstitial nephritis, anaphylaxis, angioedema, asthma, atrial arrhythmia, atrioventricular block, blindness (transient or permanent), bowel infarction, bradycardia, brain disease, bullous pemphigoid, capillary leak syndrome, cardiomyopathy, cellulitis, cerebral edema, cerebral lesion, cerebral vasculitis, cerebrovascular accident, cholecystitis, colitis, delirium, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, endocarditis, eosinophilia, exacerbation of Crohn's disease, extrapyramidal reaction, gastritis, hematemesis, hemoptysis, hemorrhage (including cerebral, gastrointestinal, retroperitoneal, subarachnoid, subdural), hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperthyroidism, hyperuricemia, hyperventilation, hypothermia, hypoventilation, hypoxia, IgA glomerulonephritis (crescentic), increased blood urea nitrogen, increased nonprotein nitrogen, inflammatory arthritis, insomnia, intestinal necrosis, intestinal obstruction, intestinal perforation, ischemic heart disease, leukocytosis, lymphocytopenia, malignant hyperthermia, meningitis, myasthenia gravis (oculo-bulbar), mydriasis, myocarditis, myopathy, myositis, neuralgia, neuritis, neuropathy, neutropenia, optic neuritis, pancreatitis, paranoia, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolism, renal tubular necrosis, respiratory acidosis, respiratory arrest, respiratory failure, restricted systemic blood flow, rhabdomyolysis, scleroderma, seizure, shock, Stevens-Johnson syndrome, syncope, thrombosis, thyroiditis, tissue necrosis at injection site, tracheoesophageal fistula, transient ischemic attacks, urticaria, ventricular premature contractions

Baseline and periodic: CBC with differential and platelets, blood chemistries including electrolytes, renal and hepatic function tests, and chest x-ray; pulmonary function tests and arterial blood gases (baseline), thallium stress test (prior to treatment). Monitor thyroid function tests (TSH at baseline then every 2-3 months during aldesleukin treatment [Hamnvik, 2011]).

Monitoring during therapy should include daily (hourly if hypotensive) vital signs (temperature, pulse, blood pressure, and respiration rate), weight and fluid intake and output; in a patient with a decreased blood pressure, especially systolic BP <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status, and for signs of infection.

Adverse events were observed in animal reproduction studies. Use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Effective contraception is recommended for fertile males and/or females using this medication.

Applies to aldesleukin: intravenous powder for solution

Along with its needed effects, aldesleukin 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