Rasburicase is a medication used in cancer patients to manage high levels of uric acid, particularly for those at risk of or experiencing tumor lysis syndrome. This condition occurs when cancer cells break down quickly, releasing their contents into the bloodstream. Rasburicase helps prevent complications by rapidly reducing uric acid levels.
Understanding Tumor Lysis Syndrome and Rasburicase’s Role
Tumor lysis syndrome (TLS) is a complication that occurs when cancer cells are rapidly destroyed, often during chemotherapy. This rapid breakdown releases substances like potassium, phosphate, and nucleic acids into the bloodstream. These nucleic acids are then metabolized into uric acid, which can accumulate to dangerous levels.
High uric acid levels can form crystals in the kidneys, leading to acute kidney injury. Rasburicase, a recombinant enzyme, converts uric acid into allantoin, a more soluble substance. Allantoin is easier for the kidneys to excrete, preventing kidney damage from uric acid accumulation. While rasburicase effectively manages uric acid, it does not directly treat other metabolic imbalances like high potassium or phosphate levels that also occur in TLS.
How Rasburicase is Dosed
Rasburicase dosing considers several factors, including the patient’s cancer type, white blood cell count, and kidney function, to determine their risk of developing TLS. The standard FDA-approved dose for pediatric and adult patients is 0.2 mg/kg, given intravenously once daily for up to five days. This regimen manages plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies undergoing anticancer therapy that may cause tumor lysis.
However, studies and clinical guidelines suggest that lower or single fixed doses can also be effective and more cost-efficient. For instance, some protocols recommend a single fixed dose of 3 mg for intermediate-risk patients and 6 mg for high-risk patients as a preventive measure. For patients with laboratory evidence of TLS, a dose of 0.2 mg/kg per day is administered daily for three to seven days until uric acid, kidney function, and electrolyte levels normalize. Treatment duration can be adjusted based on the patient’s response and clinical needs.
Safe Administration and Monitoring
Rasburicase is administered as an intravenous infusion over 30 minutes. It is important to infuse the drug through a separate intravenous line from chemotherapy agents to avoid drug incompatibilities. If a dedicated line is not available, the line should be thoroughly flushed with saline solution between chemotherapy and rasburicase infusions.
Monitoring of uric acid levels is important during treatment with rasburicase. The drug continues to break down uric acid in blood samples after they are drawn, which can lead to falsely low readings if not handled correctly. To ensure accurate measurements, blood samples must be collected in pre-chilled tubes containing heparin, immediately placed in an ice-water bath, and processed quickly. Plasma samples should be analyzed for uric acid within four hours of collection to prevent inaccurate results.
Important Safety Information and Broader Context
Several safety considerations are important when using rasburicase. Warnings include the potential for hypersensitivity reactions, which can occur at any time during treatment, including with the first dose. These reactions can range from skin rashes to severe symptoms like bronchospasm and hypotension, necessitating immediate and permanent discontinuation of the drug.
Hemolysis, the destruction of red blood cells, is another concern, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Rasburicase is contraindicated in these individuals because it generates hydrogen peroxide as a byproduct, which can lead to severe hemolytic reactions. Patients at higher risk for G6PD deficiency, such as those of African or Mediterranean ancestry, should be screened before starting treatment. Methemoglobinemia, a condition where oxygen delivery to tissues is impaired, has also been associated with rasburicase use.
Rasburicase is approved for a single course of treatment, up to five days. Repeated courses are not routinely recommended due to the potential for the body to develop an immune response against the drug, which could reduce its effectiveness and increase the risk of allergic reactions. Additionally, allopurinol, another medication used to lower uric acid, should be stopped when rasburicase treatment begins because allopurinol inhibits uric acid formation, which is the “fuel” for rasburicase’s action.