Rasburicase is a medication used in the management of high levels of uric acid in the blood, a condition known as hyperuricemia. It's primarily utilized in the treatment of tumor lysis syndrome (TLS), which is a potentially life-threatening complication that can occur after the initiation of chemotherapy for certain types of cancer.

TLS happens when cancer cells break down rapidly, releasing their contents into the bloodstream. This can overwhelm the body's ability to process these substances, leading to metabolic imbalances, including high levels of uric acid. Rasburicase works by converting uric acid into a more soluble form that can be easily excreted by the kidneys, thus helping to prevent or manage the complications associated with TLS.

Rasburicase is a urate oxidase enzyme prepared by recombinant technology, which converts uric acid to allantoin (an inactive and soluble metabolite of uric acid).

• It is used in the initial management of plasma uric acid levels in pediatric and adult patients with:
  • leukemia,
  • lymphoma, and
  • solid tumor malignancies getting chemotherapy expected to result in tumor lysis and elevation of plasma uric acid
• It is indicated only for a single course of treatment

Read: Asymptomatic Hyperuricemia Guidelines

Rasburicase Dose in Adults

Rasburicase Dosage in the treatment of Hyperuricemia associated with malignancy:

Regular Dosing:

• The usual dose is between 0.05 to 0.2 milligrams per kilogram of body weight, given once a day through an IV.
• This treatment usually lasts for 1 to 7 days, but it can vary depending on how high the uric acid levels are and the patient's condition.
• For patients with a high risk of tumor lysis syndrome (TLS), the dose might be higher and the treatment might last longer.

Single-Dose Option:

• In some cases, a single higher dose can be given instead of daily doses.
• This can range from 0.15 milligrams per kilogram to 7.5 milligrams in total, depending on the specific situation.
• Sometimes, additional doses might be needed if the uric acid levels don't go down enough.

Prevention:

• For patients at high risk of TLS before starting cancer treatment, a single dose of 3 milligrams may be given to help prevent high uric acid levels.

Rasburicase Dose in Children

Rasburicase Dosage in the treatment of Hyperuricemia associated with malignancy:

For infants, children, and adolescents with hyperuricemia due to cancer, rasburicase is typically given through an IV. Here's how the dosing generally works:

• Multiple Dosing: According to the manufacturer's recommendations, the typical dose is 0.2 milligrams per kilogram of body weight, given once a day for up to 5 days.
• Alternate Dosing: There's also another dosing option based on different factors like the risk of tumor lysis syndrome (TLS) and the initial level of uric acid:
  • For high-risk patients with a baseline uric acid level above 7.5 milligrams per deciliter (mg/dL), the dose is also 0.2 milligrams per kilogram, given once daily.
  • For intermediate-risk patients with a baseline uric acid level below 7.5 mg/dL, the dose is 0.15 milligrams per kilogram, given once daily.
  • For low-risk patients with a baseline uric acid level below 7.5 mg/dL, the dose is 0.1 milligrams per kilogram, given once daily. In some cases, a lower dose of 0.05 milligrams per kilogram has been used successfully.

These doses are typically given once daily for 1 to 7 days, depending on the patient's uric acid levels and clinical judgment.

• Single Dose: In some situations, a single higher dose of 0.15 milligrams per kilogram may be given, with additional doses as needed based on uric acid levels.
• Prevention: In high-risk patients with certain types of blood cancers, a single dose of 0.2 milligrams per kilogram may be given to prevent TLS before starting cancer treatment.

Pregnancy Risk Factor C

• Rasburicase has a pregnancy risk factor of C, meaning adverse effects were seen in animal studies.
• It should only be used during pregnancy if the benefits to the mother are more significant than the potential risks to the fetus.

Rasburicase use during breastfeeding:

• It's uncertain whether rasburicase passes into breast milk.
• Since serious adverse reactions could occur in breastfed infants, a decision should be made regarding either stopping breastfeeding or discontinuing the drug, considering how crucial the treatment is for the mother.

Rasburicase Dose in kidney disease:

• The manufacturer's labeling for rasburicase does not include any specific adjustments in dosage for individuals with renal impairment.

Rasburicase Dose in Liver disease:

• The manufacturer's labeling for rasburicase does not specify any dosage adjustments for individuals with hepatic impairment.

Common Side Effects of Rasburicase Include:

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Headache
  • Anxiety
• Dermatologic:
  • Rash
• Endocrine & Metabolic:
  • Hypophosphatemia
  • Hypervolemia
• Gastrointestinal:
  • Nausea
  • Vomiting
  • Abdominal Pain
  • Constipation
  • Diarrhea
  • Mucositis
• Hepatic:
  • Hyperbilirubinemia
  • Increased Serum ALT
• Immunologic:
  • Antibody Development
  • Development Of Igg Antibodies
• Infection:
  • Sepsis
• Respiratory:
  • Pharyngolaryngeal Pain
• Miscellaneous:
  • Fever

Less Common Side Effects Of Rasburicase Include:

• Cardiovascular:
  • Ischemic Heart Disease
  • Supraventricular Arrhythmia
• Endocrine & Metabolic:
  • Hyperphosphatemia
• Gastrointestinal:
  • Gastrointestinal Infection
• Hematologic & Oncologic:
  • Pulmonary Hemorrhage
• Hypersensitivity:
  • Hypersensitivity
• Infection:
  • Infection
• Respiratory:
  • Respiratory Failure

Contraindications to Rasburicase Include:

• Rasburicase should not be used in individuals with a history of anaphylaxis or severe hypersensitivity to rasburicase or any component of the formulation, as well as those who have experienced a hemolytic reaction or methemoglobinemia associated with rasburicase.
• Additionally, it's contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Warnings and precaution

Hemolysis: [US Boxed Warning]

• Rasburicase carries a boxed warning regarding the risk of hemolysis, which is the breakdown of red blood cells.
• It is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to this risk.
• If hemolysis occurs, which is rare (less than 1% chance), rasburicase should be stopped immediately and permanently.
• Patients at higher risk for G6PD deficiency, such as those of African or Mediterranean descent, should undergo screening before starting therapy.
• Severe hemolytic reactions typically happen within 2 to 4 days after starting rasburicase treatment.

Hypersensitivity [US Boxed Warning]

• Rasburicase carries a boxed warning due to the risk of serious and potentially fatal hypersensitivity reactions, including anaphylaxis.
• If a patient develops such a reaction, treatment with rasburicase should be stopped immediately and permanently.
• These reactions can occur at any time during treatment, even with the initial dose.
• Signs and symptoms may include bronchospasm, chest pain or tightness, difficulty breathing, low blood pressure, oxygen deficiency, shock, or hives.
• It's important to note that the safety and effectiveness of using rasburicase for more than one treatment course have not been established.

Methemoglobinemia: [US Boxed Warning]:

• Rasburicase carries a boxed warning about the risk of methemoglobinemia, a condition where the blood contains elevated levels of methemoglobin, which reduces its ability to carry oxygen.
• While rare (less than 1% chance), if a patient develops methemoglobinemia, rasburicase treatment should be stopped immediately and permanently.
• Additionally, appropriate treatment, such as transfusion or administration of methylene blue, should be initiated promptly.

Monitor:

• Plasma Uric Acid Levels: Checked 4 hours after rasburicase administration, then every 6 to 8 hours until tumor lysis syndrome (TLS) is resolved.
• Complete Blood Count (CBC): Regularly monitored to assess for any blood abnormalities.
• G6PD Deficiency Screening: Conducted in patients at high risk for deficiency before starting treatment.
• Hypersensitivity Reactions: Patients should be closely monitored for signs of hypersensitivity reactions throughout the course of treatment.

How to administer Rasburicase?

• IV Infusion: Administered intravenously over 30 minutes; avoid giving as a bolus injection.
• No Filtering: Do not filter during infusion to ensure proper delivery of the medication.
• Flush IV Line: If unable to administer through a separate IV line, flush the IV line with at least 15 mL of saline before and after rasburicase infusion.

Timing of Administration

• Chemotherapy Timing: The optimal timing of rasburicase administration concerning chemotherapy is not specified in the manufacturer's labeling. However, in some studies, chemotherapy was given 4 to 24 hours after the first rasburicase dose. Generally, rasburicase can be administered regardless of chemotherapy timing.

Mechanism of action of Rasburicase:

• Rasburicase is a type of enzyme called recombinant urate-oxidase.
• Its role is to convert uric acid, a substance found in the body, into another compound called allantoin.
• Allantoin is inactive and soluble, which means it can be easily removed from the body.
• It's important to note that rasburicase doesn't stop the body from making uric acid; instead, it helps to change it into a form that's easier for the body to get rid of.

Onset of Action:

• Uric acid levels typically decrease within 4 hours of the initial administration of rasburicase.

Distribution:

• Pediatric Patients: The volume of distribution ranges from 110 to 127 milliliters per kilogram.
• Adults: The volume of distribution ranges from 76 to 138 milliliters per kilogram.

Half-life Elimination:

• Rasburicase has an elimination half-life of approximately 16 to 23 hours.

International Brands of Rasburicase:

• Elitek
• Fasturtec
• Rasuritek

Rasburicase brand names in Pakistan:

Rasburicase is not available in Pakistan.