Asparaginase

Asparaginase is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.

Asparaginase is used to treat acute lymphocytic lymphoma.

Asparaginase may also be used for purposes not listed in this medication guide.

You should not receive this medicine if you have ever used asparaginase and it caused severe bleeding, allergic reaction, pancreatitis, or blood clot.

Asparaginase can increase your risk of blood clot or stroke. Call your doctor at once if you have sudden numbness or weakness (especially on one side of the body), slurred speech, chest pain, pain or swelling in your leg, or if you cough up blood.

You may also develop liver or pancreas problems. Call your doctor at once if you have loss of appetite, nausea and vomiting, severe pain in your upper stomach spreading to your back, dark urine, or jaundice (yellowing of the skin or eyes).

You should not receive this medicine if you have ever used asparaginase and it caused severe bleeding, allergic reaction, pancreatitis, or blood clot.

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

• liver disease;
• diabetes (asparaginase can raise blood sugar);
• a bleeding or blood-clotting disorder;
• history of stroke; or
• history of pancreatitis.

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

It is not known whether asparaginase passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling with or without pain in your arms and legs; swelling of your face, lips, tongue, or throat.

Even if you have received asparaginase without reaction in the past, you may have an allergic reaction to the medication when you receive it again.

Call your doctor at once if you have:

• severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
• easy bruising or bleeding, unusual weakness;
• sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
• chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
• pain, swelling, warmth, or redness in one or both legs;
• severe headache, blurred vision, buzzing in your ears, confusion, change in mental status, vision loss, seizure (convulsions);
• dark urine, jaundice (yellowing of the skin or eyes); or
• high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss).

Common side effects may include:

• increased thirst and urination.

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.

The following serious adverse reactions occur with Elspar treatment [see WARNINGS AND PRECAUTIONS]:

• Anaphylaxis and serious allergic reactions
• Serious thrombosis
• Pancreatitis
• Glucose intolerance
• Coagulopathy
• Hepatotoxicity and abnormal liver function
• Posterior Reversible Encephalopathy Syndrome (PRES)
• Risk of Medication Errors

The most common adverse reactions with Elspar are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases.

Clinical Trials and Post-Marketing Experience

The adverse reactions included in this section were identified in single-arm clinical trials in which Elspar was administered as part of a multi-agent regimen or from spontaneous post-marketing reports or published literature.

Because these adverse events were identified in clinical trials that were not designed to isolate the adverse effects of Elspar or were 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.

Anaphylaxis and serious allergic reactions. Allergic reactions have occurred with the first dose and with subsequent doses of Elspar. The risk of serious allergic reactions appears to be higher in patients with prior exposure to Elspar or other Escherichia coli-derived L-asparaginases.

Serious thrombosis, including sagittal sinus thrombosis

Pancreatitis, in some cases fulminant or fatal

Glucose intolerance, in some cases irreversible

Coagulopathy, including increased prothrombin time, increased partial thromboplastin time, and decreased fibrinogen, protein C, protein S and antithrombin III. CNS hemorrhages have been reported.

Hepatotoxicity, in some cases fatal, can occur.

Central Nervous System effects including coma, seizures, and hallucinations.

Azotemia, liver function abnormalities, including hyperbilirubinemia, and elevated transaminases.

Hyperammonemia, diabetic ketoacidosis, and hyperlipidemia including hypertriglyceridemia and hypercholesterolemia

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity, defined as development of binding and/or neutralizing antibodies to the product.

Elspar is a bacterial protein and can elicit antibodies in patients treated with the drug. In 2 prospectively designed clinical trials (N=59 and 24), approximately one quarter of the patients developed antibodies that bound to Elspar as measured by enzyme-linked immunosorbent assays (ELISA). Clinical hypersensitivity reactions to Elspar in studies were common ranging from 32.5% to 75%. In these studies, concomitant medications and dosing schedules varied. Patients with hypersensitivity reactions were more likely to have antibodies than those without hypersensitivity reactions. Hypersensitivity reactions have been associated with increased clearance of Elspar. Incidence of antibody formation was lower upon first administration of Elspar than second administration. The frequency of antibody formation in adults relative to children is unknown. There is insufficient information to comment on neutralizing antibodies; however, higher levels of antibody correlated with a decrease in asparaginase activity.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications and underlying disease. Therefore, comparison of the incidence of antibodies to Elspar with the incidence of antibodies to other products may be misleading.

Advise patients to contact health care professional immediately to report any of the following:

• swelling of the face, arms or legs, with or without pain in the arm or leg
• acute difficulty in breathing/shortness of breath
• severe headache, seizures, change in mental status
• new onset chest pain
• severe abdominal pain

Advise patients to inform their healthcare professional of:

• excessive thirst or an increase in the volume or frequency of urination
• pregnancy

Asparaginase is a prescription medicine approved for use with other chemotherapy drugs to treat a certain type of acute lymphocytic leukemia (ALL is a type of cancer of the white blood cells). Asparaginase belongs to a group of drugs called enzymes. This specific enzyme works by interfering with natural substances necessary for cancer cell growth.

Asparaginase comes as a solution that is injected into a vein (IV) or muscle (IM) by a healthcare provider at a medical facility.

Common side effects of asparaginase include serious hypersensitivity reactions, nausea, vomiting, and elevated blood sugar levels.

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

• are allergic to asparaginase, pegaspargase (Oncaspar), or any other medicines
• have or ever had pancreatitis (inflammation of the pancreas), liver disease, diabetes, blood clots, or severe bleeding
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

If asparaginase 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.

Contact your doctor if you miss an appointment for your asparaginase injection.

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 a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• 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.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Feeling confused.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Chest pain or pressure.
• Shortness of breath.
• Very bad headache.
• Feeling very tired or weak.
• Very bad dizziness or passing out.

Asparaginase has been assigned to pregnancy category C. Animal studies have revealed evidence of resorptions, gross abnormalities, skeletal abnormalities, and embryotoxicity. Use of asparaginase in animal testing has also been reported to retard the weight gain of mothers and fetuses. There are no controlled data in human pregnancy. Use of asparaginase is only recommended during pregnancy if the potential benefit justifies the potential risk.