Erwinia asparaginase is an enzyme used in medical treatments, particularly in the treatment of certain types of cancer. It's derived from the bacterium Erwinia chrysanthemi. This enzyme is used to lower the levels of the amino acid asparagine in the body.

Asparagine is a non-essential amino acid, meaning that the body can synthesize it on its own. However, certain types of cancer cells, such as lymphoblastic leukemia cells, are unable to produce sufficient amounts of asparagine due to their limited synthetic capabilities. These cancer cells become reliant on external sources of asparagine for their growth and survival.

Erwinia asparaginase works by breaking down asparagine into aspartic acid and ammonia, effectively depriving the cancer cells of the asparagine they need. This can inhibit the growth of the cancer cells and ultimately lead to their death.

Erwinia asparaginase is an anticancer (chemotherapeutic) drug that is used to treat acute lymphoblastic leukemia in combination with other chemotherapeutic drugs.

Erwinia asparaginase Uses:

• Acute lymphoblastic leukemia:
  • Used in treatment (in combination with other chemotherapy) of acute lymphoblastic leukemia (ALL) in patients with hypersensitivity to E. coli-derived asparaginase.

Erwinia asparaginase Dose in adults

Note: If you're giving the drug through an IV, it's a good idea to check the drug's levels in the blood. If the levels aren't where they should be, you might need to switch to giving the drug as a shot into the muscle.

Erwinia asparaginase Dose in the treatment of Acute lymphoblastic leukemia (ALL): IM, IV:

If replacing pegaspargase:

• Give 25,000 units/m^2 of Erwinia asparaginase.
• Do this three times a week (like on Monday, Wednesday, and Friday)
• Do this for 6 times in total, for every pegaspargase dose you were planning to give.

If replacing asparaginase from E. coli:

• Give 25,000 units/m^2 of Erwinia asparaginase for every planned dose of the E. coli asparaginase.

Erwinia asparaginase Dose in Childrens

Note: If you're giving the drug through an IV, it's a good idea to check the drug's levels in the blood. If the levels aren't where they should be, you might need to switch to giving the drug as a shot into the muscle.

Erwinia asparaginase Dose in the treatment of Acute lymphoblastic leukemia (ALL):

For treating ALL in children and adolescents:

• When replacing pegaspargase:
  • Give a dose of 25,000 units/m^2.
  • Administer this dose three times a week (on Monday, Wednesday, and Friday).
  • Continue this for a total of 6 doses, in place of every planned pegaspargase dose.
• When replacing asparaginase made from E. coli:
  • Give a dose of 25,000 units/m^2.
  • This dose replaces each scheduled E. coli asparaginase dose.

Erwinia asparaginase Dose in the treatment of Acute lymphoblastic leukemia (ALL) induction:

For treating ALL induction in infants, kids, and teens under 14 years:

• Give a dose of 6,000 units/m^2.
• Administer this dose three times a week.
• Do this for a total of 9 doses.
• Start giving this from the 4th day of the first week.
• This treatment is given together with other drugs: allopurinol, vincristine, prednisone, methotrexate, and daunorubicin.

Erwinia asparaginase Dosage adjustment for toxicity:

Manufacturer's Labeling For Kids & Teens:

• Blood issues (hemorrhagic or thrombotic events): Stop treatment. Can restart once symptoms are gone.
• Pancreatitis (inflamed pancreas):
  • Mild: Pause treatment until things are normal. Restart after.
  • Severe: Stop treatment. Don't use again.
• Strong allergic reactions: Stop treatment.

Recommendations for asparaginase products (Stock 2011) For Older Teens:

• Too much ammonia (hyperammonemia):
  • Level 2: Keep going.
  • Level 3: Reduce dose by 25%.
  • Level 4: Reduce dose by 50%.
• High blood sugar (hyperglycemia):
  • Manageable: Keep going.
  • Needs insulin: Pause treatment. Resume once controlled.
  • Very high or urgent: Pause treatment. Don't make up for missed doses.
• Allergic reactions:
  • Mild: Continue.
  • Severe: Stop treatment.
• High triglycerides (fat in blood):
  • Below 1000 mg/dL: Keep going but watch closely.
  • Above 1000 mg/dL: Pause treatment.
• Pancreatitis:
  • High enzyme levels only: Continue.
  • Mild symptoms: Pause until levels stabilize.
  • Severe symptoms: Stop treatment.
• Brain issues due to blood clots or bleeding:
  • Mild issues: Keep going.
  • Moderate issues: Reduce dose or space out treatments.
  • Severe issues: Stop treatment.
• Blood issues outside the brain:
  • Clotting without other symptoms: Keep going.
  • Severe clotting or bleeding: Pause or adjust treatment.

Pregnancy Risk Factor C

• In animal reproduction studies, negative effects on the offspring or developing animals were observed.
• This suggests that the substance being studied might have harmful effects on pregnancy, fetal development, or the young animals.
• However, these results from animal studies don't always directly translate to humans.
• More research is needed to understand the potential risks for human pregnancy and development.

Use of Erwinia paraginase during breastfeeding

• We don't know if asparaginase Erwinia chrysanthemi gets into breast milk.
• Because there might be serious side effects for a baby who is breastfed, the company suggests either stopping breastfeeding or not taking the drug.
• It's important to consider how necessary the treatment is for the mother.

Erwinia asparaginase Dose in Kidney Disease:

• This means that the manufacturer hasn't provided any specific changes to the drug's dosage for people with kidney problems.

Erwinia asparaginase Dose in Liver disease:

For liver enzymes (ALT/AST levels):

• If ALT/AST is between 3 to 5 times the upper normal limit (ULN): Continue with the treatment as usual.
• If ALT/AST is between 5 to 20 times ULN: Wait to give the next dose until these enzymes drop to less than 3 times ULN.
• If ALT/AST goes above 20 times ULN and stays there for more than a week: Stop the treatment.

For direct bilirubin (a specific liver test):

• If it's below 3 mg/dL: Continue with the treatment as usual.
• If it's between 3.1 to 5 mg/dL: Pause the treatment and only continue once it drops below 2 mg/dL. Think about using a different asparaginase product.
• If it goes above 5 mg/dL: Stop using asparaginase, don't use other similar drugs, and don't try to make up for any missed doses.

Common Side Effects of Erwinia asparaginase:

• Hypersensitivity:
  • Hypersensitivity reaction includes
    • Anaphylaxis
    • Urticaria

Less Common Side Effects of Erwinia asparaginase:

• Cardiovascular:
  • Thrombosis includes
    • Pulmonary embolism and cerebrovascular accident
• Endocrine & metabolic:
  • Abnormal transaminase
  • Decreased glucose tolerance
  • Hyperglycemia
• Gastrointestinal:
  • Vomiting
  • Pancreatitis
  • Abdominal pain
  • Diarrhea
  • Nausea
  • Mucositis
• Local:
  • Injection site reaction
• Miscellaneous:
  • Fever

Contraindications to Erwinia asparaginase:

This is information about when not to use asparaginase (Erwinia):

• If someone has had:
  • Severe allergic reactions, like anaphylaxis, to asparaginase (Erwinia) or any part of the drug.
  • Serious pancreas problems, serious blood clotting, or major bleeding events with a previous asparaginase treatment.
• Specific to Canada:
  • The drug shouldn't be used by women who are pregnant or might become pregnant. (This warning isn't in the US guidelines.)

Warnings and precautions

Glucose intolerance

• Some people (5% in studies) developed problems with processing sugar while on the treatment, and this issue might not go away.
• It's important to regularly check blood sugar levels before and during treatment.
• Some patients might need insulin to manage their blood sugar.

Hypersensitivity reactions

• In studies, 5% of patients had serious allergic reactions, including the severe type called anaphylaxis, while on the treatment.
• Make sure to have treatments for allergic reactions on hand when taking this medicine.
• If someone has a serious allergic reaction, stop the medicine and give the right medical treatment right away.

Pancreatitis

• In studies, 4% of patients had pancreatitis (an inflamed pancreas) while on the treatment.
• If someone shows signs of pancreatitis, check them out quickly.
• For a mild case, pause the treatment until everything is back to normal, then it might be okay to restart.
• But if it's a severe case, where there's strong belly pain for more than 3 days and very high amylase levels, stop the medicine.
• If they're diagnosed with severe pancreatitis, don't use the medicine again.

Hemorrhage and thrombosis:

• Serious blood clots, like ones in the brain and lungs, have been reported with this medicine.
• If someone gets a blood clot, stop the medicine and only think about starting again after the issue is resolved.
• Also, after 2 weeks of injections, some patients have seen drops in certain blood factors.
• If there's a bleeding event, stop the medicine and only consider restarting once the problem's resolved.
• But if someone has had serious blood clots or bleeding from previous use of this medicine, it shouldn't be used again.

Erwinia asparaginase: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Blood Tests:

• CBC (Complete Blood Count) with details.
• Amylase (checks the pancreas).
• Lipase (another check for the pancreas).
• Triglycerides (type of fat in blood).
• Liver tests.
• Blood sugar levels.
  • Do these tests before starting and then regularly during treatment.

If Giving Through IV:

• Think about checking NSAA levels.

What to Watch For:

• Signs of allergic reactions.
• Signs of pancreatitis (like belly pain).
• Signs of blood clots or bleeding.

How to administer Erwinia asparaginase?

Important Batch Note:

• Some vials, depending on their batch, should:
  • Only be given as a shot into the muscle.
  • Use a 0.2 micron filter if given through an IV.
• Check specific batches on the website: erwinazesupply.com/product-updates/.

For Shots (IM):

• Don't give more than 2 mL at one injection spot.
• If you need to give more than 2 mL, split it into multiple shots.

For IV (Into the Vein):

• Let the medicine go in over 1 to 2 hours.
• Don't mix other medicines in the same IV line.

Mechanism of action of Erwinia asparaginase:

• Asparaginase changes asparagine (a type of amino acid) into two things: aspartic acid and ammonia. This process decreases the amount of asparagine in the body.
• Leukemia cells need asparagine, but they can't make it on their own.
• By using Asparaginase, we take away the asparagine that leukemia cells need, causing them to die. This is specifically harmful only to the leukemia cells and not to the regular cells.

Think of it like taking away the food source of an enemy, causing them to starve and eventually perish.

Half-life elimination:

• When given as a shot (IM): It takes about 16 hours for half of the medicine to be gone from the body.
• When given into the vein (IV): It takes about 7.5 hours for half of the medicine to be gone from the body.

International Brand Names of Erwinia asparaginase:

• WErwinase
• Erwinaze

Erwinia asparaginase Brand Names in Pakistan:

Not Available.