Aldesleukin is a recombinant analog of interleukin-2 used to induce an adaptive immune response in the treatment of renal cell carcinoma. Aldesleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli tendon. সহজ বাংলা: মাংসপেশি/টেনডনে টান।" data-rx-term="strain" data-rx-definition="A strain is injury to a muscle or tendon. সহজ বাংলা: মাংসপেশি/টেনডনে টান।">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) Aldesleukin 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.
Mechanism of action
Aldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, in which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate the growth and differentiation of T cells.
Used to treat renal cell carcinoma, Aldesleukin induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates the growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
Indications
- For treatment of adults with metastatic renal cell carcinoma.
- Metastatic Melanoma
- Metastatic Renal Cell Carcinoma ( mRCC)
Use in Cancer
Aldesleukin is approved to treat adults with:
- Melanoma that has metastasized (spread to other parts of the body).
- Renal cell carcinoma (a type of kidney cancer) has metastasized.
Aldesleukin is also called interleukin-2 (IL-2).
Aldesleukin is also being studied in the treatment of other types of cancer.
Contraindications
The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:
- a bacterial infection
- an infection due to a fungus
- opportunistic fungal infection
- an infection due to a protozoa organism
- spread of cancer to the brain or spinal cord
- untreated decreased level of thyroid hormones
- thyroid gland infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation
- insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes
- disease in which the body has an immune response against itself
- confusion
- toxic psychosis
- repeated seizures with unconsciousness between episodes
- myasthenia gravis, a skeletal muscle disorder
- method of removing waste/poison from blood with dialysis
- a heart attack
- angina, a type of chest pain
- bacterial infection of the heart valve
- pericardial tamponade, a disorder of the heart
- supraventricular tachycardia
- rapid ventricular heartbeat
- atrial fibrillation
- slow heartbeat
- abnormal heart rhythm
- capillary leak syndrome, a condition where fluid leaks out of small blood vessels
- low blood pressure
- fluid in the lungs
- lung failure causing loss of breath
- Crohn’s disease
- an ischemic bowel, a condition where the blood flow to the intestine is significantly decreased
- a hole in the intestine
- liver problems
- infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation of the gallbladder
- bleeding of the stomach or intestines
- glomerulonephritis, a condition that affects the kidneys
- bullous pemphigoid
- scleroderma, hardening and tightening of the skin and connective tissues
- pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis
- coma
- mental status changes
- seizures
- visible water retention
- decreased urine production
- a patient who is producing milk and breastfeeding
- decreased blood volume
- inflammation of blood vessels that carry blood in the brain
- sepsis
- chronic kidney disease stage 5 (failure)
- kidney disease with likely reduction in kidney function
Dosage
Strengths: 22000000 intl units
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
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
DOSE MODIFICATIONS FOR TOXICITY:
- Decisions to stop, hold, or restart therapy should be made after performing a global patient assessment; dose reductions are not recommended.
- Life-threatening toxicities may be ameliorated with IV dexamethasone, which may also cause this drug to lose its therapeutic effects
RETREATMENT IS CONTRAINDICATED IN PATIENTS WHO HAVE EXPERIENCED THESE TOXICITIES:
CARDIOVASCULAR:
- Sustained ventricular tachycardia (5 beats or greater)
- Cardiac rhythm disturbances not controlled or unresponsive to management
- Chest pain with ECG changes, consistent with angina or myocardial infarction
- Cardiac tamponade
RESPIRATORY:
- Intubation for longer than 72 hours
GENITOURINARY:
- Renal failure requiring dialysis longer than 72 hours
NERVOUS SYSTEM:
- Coma or toxic psychosis lasting longer than 48 hours
- Repetitive or difficult-to-control seizures
GASTROINTESTINAL:
- Bowel ischemia/perforation
- GI bleeding requiring surgery
DOSES SHOULD BE HELD AND RESTARTED ACCORDING TO THE FOLLOWING:
CARDIOVASCULAR:
- Hold dose for atrial fibrillation, supraventricular tachycardia, or bradycardia that requires treatment or is recurrent or persistent; subsequent doses may be given if the patient is asymptomatic with full recovery to normal sinus rhythm.
- Hold dose for systolic BP less than 90 mm Hg with increasing requirements for pressors; subsequent doses may be given if systolic BP is 90 mm Hg or greater and stable or improving requirements for pressors
- Hold dose for any ECG change consistent with MI, ischemia, or myocarditis with or without chest pain, suspicion of cardiac ischemia; subsequent doses may be given if the patient is asymptomatic, MI and myocarditis have been ruled out, clinical suspicion of angina is low; there is no evidence of ventricular hypokinesia
RESPIRATORY:
- Hold dose for O2 saturation less than 90%; subsequent doses may be given if O2 saturation is greater than 90%
NERVOUS SYSTEM:
- Hold dose for mental status changes including moderate confusion or agitation; subsequent doses may be given if mental status changes are completely resolved
BODY AS A WHOLE:
- Hold dose for sepsis syndrome (patient is clinically unstable); subsequent doses may be given if sepsis syndrome has resolved, the patient is clinically stable, and the infection is being treated
GENITOURINARY:
- Hold dose for serum creatinine greater than 4.5 mg/dL or serum creatinine of 4 mg/dL or greater in the presence of severe volume overload, acidosis, or hyperkalemia; subsequent doses may be given if serum creatinine is less than 4 mg/dL and fluid and electrolyte status is stable
- Hold dose for persistent oliguria, urine output of less than 10 mL/hour for 16 to 24 hours with rising serum creatinine; subsequent doses may be given if urine output is greater than 10 mL/hour with a decrease of serum creatinine greater than 1.5 mg/dL or normalization of serum creatinine
HEPATIC:
- Hold dose for signs of hepatic failure including encephalopathy, increasing ascites, liver pain, and hypoglycemia; subsequent doses may be given if all signs of hepatic failure have resolved; discontinue all further treatment for that course; a new course of therapy should be initiated no sooner than 7 weeks after cessation of adverse event and hospital discharge
Side Effects
The Most Common
- nausea
- vomiting
- diarrhea
- loss of appetite
- sores in the mouth and throat
- tiredness
- weakness
- dizziness
- general feeling of being unwell
- pain or redness at the place where the injection was given
- seizures
- chest pain
- extreme worry
- abnormal excitement or agitation
- new or worsening depression
- seeing things or hearing voices that do not exist (hallucinating)
- changes in your vision or speech
- loss of coordination
- decreased alertness
- unusual bruising or bleeding
- extreme sleepiness or tiredness
- difficulty breathing
- wheezing
- stomach pain
- yellowing of the skin or eyes
- decreased urination
- rash
- hives
- itching
- difficulty breathing or swallowing
More Common
- fever
- numbness and tingling
- signs of bleeding (e.g., blood in the urine, vomiting blood, nosebleeds, unusual bleeding or bruising)
- signs of breathing problems (e.g., shortness of breath, troubled breathing, wheezing, tightness in the chest, fast or irregular breathing)
- signs of changed mental status (e.g., confusion, irritability, or trouble speaking)
- signs of decreased red blood cell production (e.g., unusual tiredness, pale skin)
- signs of electrolyte imbalance (e.g., muscle pain or cramps, weakness, irregular heartbeat, lack of coordination, thirst, confusion)
- signs of kidney problems, such as a major decrease in urine output
- signs of liver problems (e.g., darkening of urine, pale stools, yellow eyes or skin)
- sores in the mouth and on the lips
- stomach pain
- swelling of the ankles, feet, hands
- symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odor)
- symptoms of irregular heartbeat (e.g., chest pain, dizziness, rapid, pounding heartbeat, shortness of breath)
- symptoms of low blood pressure (e.g., fainting, dizziness, lightheadedness, blurred vision, nausea)
- symptoms of low blood sugar (e.g., cold sweat, cool pale skin, headache, fast heartbeat, weakness)
- symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
Rare
- chest pain
- severe stomach pain
- signs of bleeding in the stomach (e.g., bloody, black, or tarry stools; spitting up of blood; vomiting blood or material that looks like coffee grounds)
- signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
- signs of heart complications (e.g., chest pain; changes in heart rhythm; dizziness; swelling in hands, feet, or abdomen)
- signs of infection (e.g., cough or hoarseness, sore throat, chills, fever, swollen or painful glands, unusual tiredness or weakness, painful or difficult urination)
- signs of sepsis (blood infection; e.g., fever; dizziness; chills; very high or very low body temperature; low blood pressure; pounding or rapid heartbeat; rapid, shallow breathing)
- signs of severe skin reaction (e.g., skin blisters, severe rash or itching, pinpoint red spots on the skin, blisters on the skin, white spots on lips or in the mouth)
- swollen or enlarged stomach
Drug Interactions
There may be an interaction between aldesleukin and any of the following:
- 5-ASA medications (e.g., mesalamine, olsalazine, sulfasalazine)
- alcohol
- aliskiren
- alpha-agonists (e.g., clonidine, methyldopa)
- alpha-blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, lisinopril, ramipril)
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- BCG vaccine
- beta-blockers (e.g., acebutolol, propranolol, metoprolol)
- brimonidine
- calcium channel blockers (e.g., diltiazem, nifedipine, verapamil)
- cancer medications (e.g., asparaginase, cisplatin, dacarbazine, doxorubicin, interferon-alfa, methotrexate, tamoxifen, vinblastine)
- conivaptan
- corticosteroids (e.g., prednisone, dexamethasone)
- diuretics (e.g., furosemide, hydrochlorothiazide)
- duloxetine
- hydralazine
- levodopa
- muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine)
- nitrates (e.g., isosorbide dinitrate, nitroglycerin)
- obinutuzumab
- opioid pain relievers (e.g., codeine, fentanyl, oxycodone, morphine)
- pentoxifylline
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- radiocontrast dye
- tricyclic antidepressants (e.g., clomipramine, desipramine, imipramine)
Pregnancy and Lactation
FDA pregnancy risk category C
Pregnancy
There are no adequate studies on the use of this medication by pregnant women. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately. Aldesleukin, IL-2 is classified; there are no adequate well-controlled studies of aldesleukin in pregnant women. The effects of aldesleukin therapy on fertility or pregnancy have not been studied, and it is unknown whether aldesleukin can affect reproduction capacity or cause fetal harm. Administration of aldesleukin to fertile persons of either gender not practicing effective contraception is not recommended, and aldesleukin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breast-feeding
It is not known if aldesleukin passes into breast milk. If you are breastfeeding and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. According to the manufacturer, either aldesleukin, IL-2 or breastfeeding should be discontinued because of the potential for serious adverse reactions in nursing infants from aldesleukin exposure. Aldesleukin excretion into human milk is unknown. Consider the benefits of breastfeeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
What special precautions should I follow?
Before receiving aldesleukin,
- tell your doctor and pharmacist if you are allergic to aldesleukin, any other medications, or any of the ingredients in aldesleukin injection. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: beta blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); certain cancer chemotherapy medications such as asparaginase (Elspar), cisplatin (Platinol), dacarbazine (DTIC-dome), doxorubicin (Doxil), interferon-alfa (Pegasys, PEG-Intron), methotrexate (Rheumatrex, Trexall), and tamoxifen (Nolvadex); medications for high blood pressure; medications for nausea and vomiting; narcotics and other pain medications; sedatives, sleeping pills, and tranquilizers; steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); and steroid creams, lotions, or ointments such as hydrocortisone (Cortizone, Westport). Also, tell your doctor and pharmacist about all the medications you are taking so they can check whether any of your medications may increase the risk that you will develop kidney or liver damage during your treatment with aldesleukin.
- tell your doctor if you have ever had seizures, gastrointestinal (GI) bleeding requiring surgical treatment, or other serious GI, heart, nervous system, or kidney problems after you received aldesleukin or if you have ever had an organ transplant (surgery to replace an organ in the body). Your doctor may not want you to receive aldesleukin.
- tell your doctor if you have or have ever had seizures, Crohn’s disease, scleroderma (a disease that affects the tissues that support skin and internal organs), thyroid disease, arthritis, diabetes, myasthenia gravis (a disease that weakens muscles), or cholecystitis (inflammation of the gall bladder that causes severe pain).
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while receiving aldesleukin, call your doctor. You should not breastfeed while receiving aldesleukin.
Warnings for this medication?
Autoimmune conditions: This medication may worsen any inflammatory or autoimmune conditions, including diabetes mellitus, inflammation of the thyroid, Crohn’s disease, and inflammatory arthritis.
Birth control: Women who could become pregnant and men whose partners who could become pregnant must use an effective method of birth control while using this medication.
Blood clotting: This medication can reduce the number of platelet cells in the blood. Platelets help the blood to clot, and a shortage could make you bleed more easily. Tell your doctor of any signs that your blood is not clotting as quickly as usual. Such symptoms may include black and tarry stools, blood in the urine, easy bruising, or cuts that won’t stop bleeding.
Nervous system problems: Hallucinations, speech difficulty, agitation, and changes in mental status have been reported with aldesleukin. If you experience any changes in thinking, movement or mood, contact your doctor immediately.
Diabetes: This medication may affect your blood glucose (sugar) levels. You and your doctor should monitor your sugar levels closely while using this medication.
Drowsiness/reduced alertness: Aldesleukin may affect the mental or physical abilities needed to drive or operate machinery. Avoid driving, operating machinery, or performing other potentially hazardous tasks until you have determined how this medication affects you.
Fertility: Temporary or permanent sterility may occur with the use of aldesleukin.
Heart conditions: Aldesleukin may cause damage to the heart and should not be used by people with heart disease. If you experience symptoms of heart trouble, such as chest pain, abnormal heart rhythm, sudden dizziness, fluid retention, or swelling, contact your doctor as soon as possible.
Infections: Aldesleukin may increase the risk of getting an infection. If you have an indwelling central line or have an existing infection, speak to your doctor about how to prevent infections while using this medication. If you develop any signs or symptoms of an infection (e.g., fever, cough, chest pain, difficult or painful urination, or skin redness, warmth, or swelling), contact your doctor.
Kidney function: Decreased kidney function or kidney disease may cause this medication to build up in the body, causing side effects. This medication also affects kidney function and should not be used by people with kidney disease or decreased kidney function. Your doctor will monitor your kidney function during treatment with aldesleukin with blood tests.
Liver function: This medication can affect liver function and should not be used by people with liver disease or decreased liver function. Your doctor will monitor your liver function during treatment with aldesleukin with blood tests. Report any signs of liver damage such as darkening urine, pale stools, or yellow skin or eyes to your doctor as soon as possible.
Low blood pressure: This medication can cause low blood pressure: If you experience severe dizziness, especially when standing from a lying or sitting position, contact your doctor.
Seizure disorders: Aldesleukin can cause seizures. If you have a seizure disorder, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Skin reactions: Aldesleukin has been linked to serious skin reactions. If you experience symptoms of a serious skin reaction (such as skin rash; redness of the skin; skin peeling; or blisters on the lips, eyes, or mouth) with fever, chills, headache, cough, or body aches, contact your physician immediately.
Children: The safety and effectiveness of this medication have not been established for use by children.
Seniors: Seniors may be at higher risk of experiencing the side effects of this medication.
Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breastfeeding, and any other significant facts about your health. These factors may affect how you should use this medication.
References
- https://www.ncbi.nlm.nih.gov/books/NBK548091/
- https://go.drugbank.com/drugs/DB00041
- https://medlineplus.gov/druginfo/meds/a692009.html
- https://www.drugs.com/mtm/aldesleukin.html
- https://www.webmd.com/drugs/2/drug-11667/aldesleukin-intravenous/details/list-contraindications
- https://www.pdr.net/drug-summary/Proleukin-aldesleukin-1321
- https://www.medbroadcast.com/drug/getdrug/proleukin
