Rascase contains Rasburicase, is a recombinant urate oxidase enzyme used to manage tumor lysis syndrome (TLS), a life-threatening condition caused by the rapid breakdown of cancer cells, leading to high levels of uric acid in the blood. It converts uric acid into allantoin, which is more soluble and easily excreted by the kidneys.

Mechanism of Action

Rasburicase works by:

• Converting uric acid into allantoin, a highly water-soluble compound that is easily excreted in the urine.
• Reducing uric acid levels rapidly, preventing kidney damage and metabolic complications associated with TLS.
• Bypassing xanthine oxidase, making it different from allopurinol, which only inhibits uric acid formation but does not break down existing uric acid.

Why Is Rasburicase Important in Tumor Lysis Syndrome (TLS)?

• Chemotherapy causes rapid breakdown of cancer cells, releasing uric acid, potassium, and phosphate.
• High uric acid levels can lead to acute kidney injury (AKI).
• Rasburicase helps prevent kidney damage by eliminating uric acid efficiently.

Indications (Uses of Rasburicase)

• Treatment and prevention of hyperuricemia in pediatric and adult patients with:
• Acute leukemia (ALL, AML)
• Lymphomas (Burkitt’s lymphoma, high-grade non-Hodgkin's lymphoma)
• Solid tumors with a high risk of tumor lysis syndrome

Not used for chronic hyperuricemia (like in gout) due to its short duration of action and high cost.

Rasburicase is the first-line treatment for tumor lysis syndrome due to its rapid and effective reduction of uric acid levels. It significantly reduces the risk of acute kidney injury in TLS patients undergoing chemotherapy. However, it is contraindicated in G6PD deficiency and requires careful monitoring for hemolysis and allergic reactions.

Dosage and Administration

Given as an intravenous (IV) infusion over 30 minutes, once daily.

Administer with caution in G6PD-deficient patients (risk of hemolysis).
Blood samples for uric acid levels must be kept on ice to prevent artificial degradation by rasburicase.

Clinical Efficacy

• Clinical trials have demonstrated that Rasburicase:
• Reduces uric acid levels within 4 hours.
• Prevents acute kidney injury (AKI) in TLS patients.
• Lowers need for dialysis in patients at high risk of TLS.

Study Results:

• In a Phase III study, Rasburicase reduced uric acid levels to normal in 86% of patients within 4 hours, compared to 12% with allopurinol.
• Patients receiving Rasburicase had lower creatinine levels, indicating better kidney protection.

Side Effects of Rasburicase

Common Side Effects:

• Nausea
• Vomiting
• Fever
• Headache

Serious Side Effects:

• Hemolysis (Red Blood Cell Breakdown) – Risk in G6PD-deficient patients.
• Methemoglobinemia – Decreases oxygen-carrying capacity of blood.
• Severe Allergic Reactions (Anaphylaxis, Rash, Hypotension) – Rare but possible.

Contraindications & Precautions

• Who Should NOT Receive Rasburicase?
• Patients with G6PD deficiency (high risk of hemolytic anemia).
• Pregnant or breastfeeding women (not enough safety data).
• Patients with a history of severe hypersensitivity reactions.

Precaution: Always test for G6PD deficiency before administration.

Drug Interactions

Avoid concurrent use of:

• Allopurinol (no added benefit, different mechanism).
• Other uric acid-lowering agents (combination unnecessary).
• Nephrotoxic drugs (increased risk of kidney damage).

Pharmacokinetics

• Half-life: ~18 hours (short-acting)
• Metabolism: Broken down by proteolytic enzymes.
• Elimination: Not excreted by kidneys, making it safe for renal-impaired patients.

Advantages of Rasburicase Over Other Treatments

• Fast-acting – Works within 4 hours, unlike allopurinol.
• Directly eliminates uric acid, preventing kidney injury.
• More effective in high-risk TLS patients.
• Safe for renal-impaired patients (not excreted by kidneys).