L-asparaginase: An Overview

Summary

• ‍BRAND: Elspar^®, Kidrolase^®‍
• DRUG TYPE: Anti-cancer chemotherapy drug.‍
• CONDITIONS TREATED: Lymphoma, Acute lymphocytic leukemia (ALL).‍
• ADMINISTRATION: Liquid to be injected into a large muscle or be infused into the vein.

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Definition

What is L-asparaginase?

Although some people refer to L-asparaginase as an anti-cancer drug, it is actually an enzyme extracted from bacteria rather than a synthesized chemotherapeutic drug.¹ Enzymes are proteins which catalyze or speed up biochemical reactions in body. This particular enzyme is useful as an antitumor agent because it catalyzes the breakdown of L-asparagine, a nutrient that is absolutely required for cancer cell division. The rationale behind using L-asparaginase is based on the finding that tumor cells have an unusually high requirement for L-asparagine and cannot produce enough of it; normal cells need less and are fully capable of producing this essential nutrient. Without L-asparagine, tumor cells will starve.²

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Use & Administration

What L-asparaginase is used for?

L-asparaginase is most commonly used to treat lymphoma or acute lymphocytic leukemia (ALL). It can also be used to reduce growth of mast cell tumors.

Delivery of L-asparaginase:  

• Most often, a trained health care professional will administer L-asparaginase as an injection into a large muscle (intramuscular or IM). The medication may be split into two injections, depending on the dose that the patient needs.
• The medication may also be infused into a vein (intravenous or IV); however, this type of delivery is more often associated with allergic reactions and a test dose is recommended.¹
• There is no pill form of L-asparaginase.
• Your veterinarian will determine the appropriate dose, schedule of delivery and method of administration for L-asparaginase by evaluating the patient’s height, weight, general health, type of cancer or condition being treated.

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Precautions

This drug does not usually cause side effects but can result in an allergic reaction characterized by mild signs such as hives, itching, or restlessness. Although rare, the allergic reaction could be intense and result in a serious anaphylactic shock reaction. Symptoms associated with anaphylaxis include vomiting, diarrhea, shortness of breath, decreased blood pressure and collapse.¹

Not all normal cells can rely totally on their own production of L-asparagine. Cells that normally reproduce rapidly or rely on high levels of protein synthesis are unable to grow or function normally when faced with a depletion of L-asparagine. Therefore, the actions of L-asparaginase are particularly harmful to cells of the intestine, bone marrow, liver, and pancreas and your pet may experience the following side effects:⁶

• Nausea and vomiting
• Poor appetite
• Stomach cramps
• Painless swelling of face, hands, or legs
• Fever and chills
• Central neurotoxicity: excessive sleepiness, agitation
• Disorientation, seizure or possibly coma

Less common side effects include:

• Mouth sores
• Pancreatitis which includes pain in the upper abdomen, nausea, vomiting, fever and a rapid pulse
• Blood test abnormalities such as excessive sugar levels which may indicate liver problems
• Blood clotting disorder which include an increased risk of bleeding and clotting

Let your veterinarian know if you observe any of these side effects after treatment.

Symptoms of overdose:

Since L-asparaginase is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur.³ However, if your dog has trouble breathing after the treatment, be sure to seek medical help immediately.⁴

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Interactions

As mentioned above, be sure to provide your veterinarian with a list of any drugs or supplements your pet may be taking prior to treatment with L-asparaginase. Severe interactions can arise when combined with the following:⁵

• Immunosuppressants such as talimogene laherparepvec, efalizumab or natalizumab
• Live Vaccines
• Methotrexate, Vincristine, or Prednisolone.

Methotrexate, a commonly used anti-tumor drug, and L-asparaginase work against each other and should be administered at least 48 hours apart. This is also true of vincristine, another chemotherapeutic agent, and administration of vincristine and L-asparaginase should be separated by a few days to prevent adverse interactions.⁶ Prednisolone, another anti-cancer drug, tends to increase blood sugar levels to a much greater extent when used with L-asparaginase.

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Care Tips At Home

• Since L-asparaginase is associated with allergic reactions, particularly if given using the IV method, patients are often premedicated with an antihistamine prior to delivery. Your pet should be monitored for a minimum of 1 hour following treatment.
• After cleaning up urine, feces, or vomit, wash your hands thoroughly since small amounts of the drug may be excreted in these wastes.
• Encourage your dog to drink as much water as possible during a 24-hour period, unless you are instructed otherwise.³
• To reduce nausea, ask your veterinarian to prescribe an anti-nausea medication and feed your dog small meals more frequently.
• Contact your veterinarian immediately if your dog runs a fever of 100.4 °F (38 °C) or higher, and/or has chills (intermittent shivering). These may be signs of infection.

Be sure to contact your veterinarian within 24 hours of noticing any of the following symptoms:³

• Loss of appetite and decreased food consumption which may indicate nausea
• Vomiting more than 4-5 times in a 24-hour period
• Abdominal pain or swelling which is very sensitive to touch
• Unusual bleeding or bruising
• Extreme fatigue
• Yellowing of the skin or eyes
• Unusual thirst and excessive urination
• Agitation or disorientation.

Your vet prescribed L-asparaginase after concluding that its benefits outweigh the risks, but it is important to follow their recommendations closely. If your pet experiences side effects, remember that they often have predictable durations, are reversible, and will go away after the treatment is finished. Most pets do not experience serious side effects.