Rasburicase is a medication used to manage high levels of uric acid in the blood. It is a recombinant urate-oxidase enzyme, a protein produced through genetic engineering. Specifically, the genetic instructions for making the enzyme are taken from a fungus, Aspergillus flavus, and inserted into a yeast species, Saccharomyces cerevisiae, which then produces the drug.
Medical Use for Tumor Lysis Syndrome
Rasburicase is a standard treatment for patients at high risk of Tumor Lysis Syndrome (TLS). TLS is a serious complication that can occur during cancer treatment, especially in individuals with leukemias and lymphomas. It happens when chemotherapy or other cancer therapies cause a large number of cancer cells to be destroyed rapidly, releasing their internal contents into the bloodstream. This sudden flood of cellular material includes large quantities of purines, which are then broken down into uric acid.
When uric acid levels become excessively high (hyperuricemia), it poses a threat to the kidneys. The uric acid can crystallize in the renal tubules, the small tubes in the kidneys that filter waste. This crystallization can lead to blockages, causing acute kidney injury and potentially failure. The metabolic disturbances from TLS, including high potassium and phosphate levels, can also lead to severe health issues like seizures and cardiac arrhythmias.
To prevent these outcomes, rasburicase is given to patients who are about to start chemotherapy and are considered at high risk for developing TLS. It works quickly to reduce existing uric acid in the blood, protecting the kidneys as cancer cells are broken down. This intervention helps manage the initial stages of cancer treatment for vulnerable patients.
Mechanism of Action
Rasburicase provides an enzymatic function naturally absent in humans. In many other mammals, the enzyme urate oxidase is present to break down uric acid as a final step in purine metabolism. Humans, however, lack this enzyme, making uric acid the final product of this pathway in our bodies.
Rasburicase is a manufactured version of the urate oxidase enzyme. It directly targets and catalyzes the enzymatic oxidation of existing uric acid in the bloodstream. During this chemical reaction, the poorly soluble uric acid is converted into a different compound called allantoin. A key feature of allantoin is that it is five to ten times more soluble in water than uric acid.
This significant increase in solubility allows the allantoin to be easily and efficiently filtered by the kidneys and excreted from the body in urine. The byproducts of this conversion are carbon dioxide and hydrogen peroxide. By transforming uric acid into a substance that the body can readily dispose of, rasburicase rapidly lowers plasma uric acid levels, often within hours of administration.
Administration and Monitoring
Rasburicase is administered to patients in a hospital or clinical setting under the supervision of a physician trained in cancer therapy. The medication is given as an intravenous (IV) infusion, typically diluted in a 50mL bag of 0.9% sodium chloride and infused over a period of 30 minutes. It is important that the IV line used for rasburicase is separate from lines used for chemotherapy agents to prevent any potential drug incompatibilities.
The dosage is calculated based on the patient’s body weight, with a common dose being 0.2 mg per kilogram of body weight per day. Treatment is often short-term, and in many cases, a single dose is sufficient to effectively reduce uric acid levels. The duration of treatment can extend up to seven days, depending on the patient’s clinical situation and uric acid measurements.
Close monitoring ensures the drug is working as intended. Healthcare providers regularly check the patient’s uric acid levels. Special procedures are required for blood sample collection; the blood must be drawn into pre-chilled tubes and immediately placed in an ice bath to prevent the rasburicase in the sample from continuing to break down uric acid outside the body, which would cause an inaccurately low reading.
Adverse Effects and Contraindications
Rasburicase treatment carries potential risks and side effects. Common adverse reactions can include nausea, vomiting, headache, and fever. More serious complications can occur, such as severe allergic reactions, including anaphylaxis. If a patient shows signs of an allergic reaction, the treatment must be stopped immediately and permanently.
A significant contraindication for rasburicase use is a genetic condition known as Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. Individuals with G6PD deficiency lack this enzyme, which protects red blood cells from damage. One byproduct of rasburicase’s action is hydrogen peroxide. In patients with G6PD deficiency, this hydrogen peroxide can cause severe destruction of red blood cells (hemolysis).
This can lead to hemolytic anemia and methemoglobinemia, a disorder where the iron in hemoglobin is changed, preventing it from effectively releasing oxygen to the body’s tissues. For these reasons, it is often recommended that patients, particularly those from populations with a higher prevalence of the condition, be screened for G6PD deficiency before receiving rasburicase.