Usage
Rasburicase is prescribed for the initial management of elevated plasma uric acid levels (hyperuricemia) in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy. This is particularly important in the context of Tumor Lysis Syndrome (TLS), where rapid tumor cell breakdown releases large amounts of uric acid, potentially leading to kidney damage. Pharmacologically, rasburicase is classified as a uricolytic agent. It works by catalyzing the enzymatic oxidation of uric acid into allantoin, a more soluble compound that is easily excreted by the kidneys.
Alternate Names
Rasburicase is also known as recombinant urate oxidase. Brand names include Elitek and Fasturtec.
How It Works
Pharmacodynamics: Rasburicase mimics the action of the naturally occurring enzyme urate oxidase, which is absent in humans. It catalyzes the conversion of uric acid to allantoin, significantly reducing plasma uric acid levels. This prevents the formation of uric acid crystals in the kidneys, reducing the risk of acute renal failure.
Pharmacokinetics:
- Absorption: Administered intravenously, rasburicase achieves steady-state levels within 2-3 days of daily dosing.
- Metabolism: Rasburicase, being an enzyme itself, is not significantly metabolized by CYP450 enzymes.
- Elimination: The primary route of elimination is not entirely understood. While a small amount is eliminated renally as allantoin, the complete elimination pathway has not been completely elucidated. The elimination half-life is approximately 18-22 hours.
Mode of Action: Rasburicase directly acts on uric acid in the bloodstream. It does not involve receptor binding, enzyme inhibition (other than its uricolytic action on uric acid), or neurotransmitter modulation.
Dosage
Standard Dosage
Adults: 0.2 mg/kg administered as a 30-minute intravenous infusion once daily for up to 5 days.
Children: 0.15 - 0.2 mg/kg (up to a maximum of 6 mg) administered as a 30-minute intravenous infusion once daily for up to 5 days. In certain cases, such as Burkitt’s Lymphoma with bulky disease, twice-daily dosing may be considered at the discretion of the consultant. For children under 30 kg with uric acid levels within or below the normal range, some institutions cap the dose at 3 mg. For those 30 kg or over, or with elevated uric acid, a dose of 6 mg may apply.
Special Cases:
- Elderly Patients: No specific dose adjustment is generally recommended. Close monitoring of renal function is advised. Single, lower fixed doses of rasburicase (e.g., 3-6 mg) have been explored in elderly patients with hyperuricemia, with subsequent doses as needed.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Careful monitoring is necessary. No specific dose adjustments are universally recommended, but clinical judgment should be used.
Clinical Use Cases
Rasburicase dosing remains consistent across these clinical settings, focusing on the hyperuricemia management aspect. Its use is tied to the risk of TLS and not specifically to procedures like intubation, mechanical ventilation, or surgical procedures. It is frequently used in ICUs to manage TLS in critically ill patients. In emergency situations where rapid uric acid reduction is crucial, rasburicase is the preferred uricolytic agent.
Dosage Adjustments
Dose adjustments are not routinely made for renal or hepatic impairment. However, for patients with G6PD deficiency, rasburicase is contraindicated.
Side Effects
Common Side Effects:
Nausea, vomiting, fever, headache, abdominal pain, constipation, diarrhea, mucositis (inflammation of the mucous membranes), rash, peripheral edema, anxiety, pharyngolaryngeal pain, elevated alanine aminotransferase.
Rare but Serious Side Effects:
Hypersensitivity reactions (including anaphylaxis), hemolysis (destruction of red blood cells), methemoglobinemia (a blood disorder affecting oxygen transport).
Long-Term Effects:
Limited data exist regarding long-term side effects, as rasburicase is typically given as a short course. Development of antibodies to rasburicase may occur with repeated exposure, potentially reducing the drug’s efficacy in subsequent courses.
Adverse Drug Reactions (ADR):
Anaphylaxis, hemolytic anemia, methemoglobinemia.
Contraindications
- History of anaphylaxis, severe hypersensitivity, hemolysis, or methemoglobinemia to rasburicase.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Drug Interactions
Rasburicase, being an enzyme, has limited drug interactions via CYP450 mechanisms. However, it can interact with agents that can induce methemoglobinemia (e.g., local anesthetics such as benzocaine, prilocaine, dapsone, nitric oxide). Concomitant use of allopurinol with rasburicase is usually avoided and generally not recommended due to their differing mechanisms of action.
Pregnancy and Breastfeeding
- Pregnancy: Rasburicase is categorized as Pregnancy Category C in the U.S. Animal studies have demonstrated teratogenic effects. Its use in pregnancy should be reserved for situations where the benefits clearly outweigh the risks.
- Breastfeeding: It is unknown if rasburicase is excreted in breast milk. Breastfeeding is not recommended during treatment and for 2 weeks after the last dose.
Drug Profile Summary
- Mechanism of Action: Catalyzes the conversion of uric acid to allantoin.
- Side Effects: Nausea, vomiting, fever, headache, allergic reactions, hemolysis, methemoglobinemia.
- Contraindications: Hypersensitivity to rasburicase, G6PD deficiency.
- Drug Interactions: Drugs that can induce methemoglobinemia (e.g., some local anesthetics).
- Pregnancy & Breastfeeding: Category C; breastfeeding not recommended.
- Dosage: 0.2 mg/kg/day IV for up to 5 days in adults and 0.15-0.2 mg/kg/day IV for up to 5 days (maximum 6mg/day) in children.
- Monitoring Parameters: Uric acid levels, complete blood count, methemoglobin levels, renal function tests.
Popular Combinations
Rasburicase is often used in conjunction with aggressive intravenous hydration to enhance uric acid excretion and prevent kidney damage. It is usually given alone, with administration of other hypouricemic agents being unnecessary during treatment.
Precautions
- General Precautions: Evaluate patients for G6PD deficiency and hypersensitivity to rasburicase before initiating treatment. Closely monitor uric acid levels, complete blood count, and renal function.
- Specific Populations: Use with caution in pregnant women. Breastfeeding is not recommended. Careful monitoring is advised in elderly patients.
- Lifestyle Considerations: No specific lifestyle changes are routinely required.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rasburicase?
A: For adults, the standard dose is 0.2 mg/kg IV once daily for up to 5 days. For children, the dose is 0.15-0.2 mg/kg IV once daily (max 6mg/day) for up to 5 days.
Q2: How is Rasburicase administered?
A: Rasburicase is given as a 30-minute intravenous infusion. It should not be administered as a bolus injection.
Q3: What is the mechanism of action of Rasburicase?
A: Rasburicase catalyzes the oxidation of uric acid into allantoin, a more soluble compound that is readily excreted by the kidneys.
Q4: What are the common side effects of Rasburicase?
A: Common side effects include nausea, vomiting, fever, headache, abdominal pain, and rash.
Q5: What are the serious side effects of Rasburicase?
A: Rare but serious side effects include hypersensitivity reactions (including anaphylaxis), hemolysis, and methemoglobinemia.
Q6: Can Rasburicase be used in patients with renal insufficiency?
A: Yes, no dose adjustment is needed for patients with renal impairment.
Q7: Is Rasburicase safe to use during pregnancy?
A: Rasburicase is Pregnancy Category C. Animal studies have shown adverse effects. Its use during pregnancy should be reserved for cases where the potential benefits outweigh the risks.
Q8: What is the role of Rasburicase in Tumor Lysis Syndrome (TLS)?
A: Rasburicase is used to prevent and manage hyperuricemia associated with TLS, reducing the risk of uric acid nephropathy and acute kidney injury.
Q9: Can Rasburicase be used with allopurinol?
A: Concomitant use of allopurinol is generally avoided and not recommended as they work via different mechanisms (rasburicase metabolizes existing uric acid; allopurinol reduces uric acid formation). If ongoing hypouricemic treatment is required after the rasburicase course ends, allopurinol can be considered.
Q10: How should uric acid levels be monitored during Rasburicase treatment?
A: Due to rasburicase degrading uric acid in vitro, special precautions are required for blood sampling and processing to avoid falsely low readings. Blood samples should be chilled immediately and assayed within 4 hours.
