Peg-asparaginase

Uses

Peg-asparaginase is a modified form of L-asparagine amidohydrolase used to treat acute lymphoblastic leukemia, which is dependent on an external source of asparagine.

For treatment of acute lymphoblastic leukemia

Peg-asparaginase is also used to associated treatment for these conditions: Acute Lymphoblastic Leukaemias (ALL)

How Peg-asparaginase works

Peg-asparaginase, more effective than asparaginase, converts asparagine to aspartic acid and ammonia. It facilitates production of oxaloacetate which is needed for general cellular metabolism. Some malignant cells lose the ability to produce asparagine and so the loss of exogenous sources of asparagine leads to cell death.

Toxicity

Adverse effects that occur more than 10% of the time include hepatotoxicity as it is known to increase serum transaminases (ALT, AST). Also known to induce hypersensitivity reactions including anaphylaxis, erythema and bronchospasm.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Alcohol and pegaspargase can both cause hepatoxicity, therefore if they are used together they may have additive hepatoxic effects.

Peg-asparaginase Alcohol interaction

[Moderate]

Concomitant use of asparaginase with other hepatotoxic agents may potentiate the risk of liver injury.

Asparaginase-associated hepatotoxicity has been reported more commonly in adults than in children and has been strongly associated with obesity.

Hepatomegaly, acute severe hepatotoxicity, and fatal liver failure have been reported with asparaginase treatment in adults.

Also, asparaginase may increase the toxicity of drugs bound to plasma proteins or metabolized by the liver.

The risk of additive hepatotoxicity should be considered when asparaginase is used with other hepatotoxic agents (e.g., alcohol, androgens, antituberculosis agents, azole antifungal agents, ACE inhibitors, macrolide antibiotics, nonsteroidal anti-inflammatory agents, nucleoside reverse transcriptase inhibitors, sulfonamides, thiazolidinediones, and statins).

Liver function tests should be monitored at regular intervals during asparaginase treatment with or without other hepatotoxic drugs.

Patients should be advised to seek medical attention if they experience potential symptoms of hepatotoxicity such as right upper quadrant pain, increasing abdominal size, fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, dark urine, pale stools, and jaundice.

Peg-asparaginase Drug Interaction

Moderate: contained in alcoholic beverages , aspirin/citric acid/sodium bicarbonate, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, acetaminophen, thioguanineUnknown: charcoal, pemetrexed, RHO Immunoglobulin , multivitamin with minerals, lorazepam, diphenhydramine, dicyclomine, iodine i 131 tositumomab, bumetanide, meperidine, pantoprazole, vitamin a topical, ondansetron

Peg-asparaginase Disease Interaction

Major: bleeding disorders, pancreatic dysfunctionModerate: hepatic dysfunction, hyperglycemia

Volume of Distribution

IV: Adults (asparaginase naive): 2.4 L/m2 Distributes into CSF (reportedly reducing CSF asparagine concentrations to a similar extent as asparaginase

Elimination Route

Onset of Asparagine depletion by IM is within 4 days Time to peak: IM: 3 to 4 days

Half Life

IM: ~6 days; half-life decreased to ~3 days (range: 1.4 to 5 days) in patients with previous hypersensitivity to native L-asparaginase; IV: Adults (asparaginase naive): 7 days

Innovators Monograph

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