How should I prepare a 7.5 mg dose of rasburicase for infusion over 30 minutes using five 1.5 mg vials?

Rasburicase 7.5 mg Preparation and Administration

Reconstitute each of the five 1.5 mg vials with the provided diluent, then combine all five reconstituted vials in a 50 mL bag of 0.9% sodium chloride and infuse over 30 minutes. 1

Step-by-Step Preparation Protocol

Reconstitution of Individual Vials

• Each 1.5 mg vial must be reconstituted with 1 mL of the provided diluent (supplied in the kit) 1
• Gently swirl each vial—do not shake vigorously, as rasburicase is a protein that can denature with aggressive agitation 1
• Visually inspect each reconstituted solution for particulate matter and discoloration before proceeding 1
• Each reconstituted vial will contain 1.5 mg/mL rasburicase 1

Dilution for Infusion

• Withdraw the entire contents from all five reconstituted vials (total volume = 5 mL containing 7.5 mg rasburicase) 1
• Inject this 5 mL into a 50 mL bag of 0.9% sodium chloride for injection 1
• Gently invert the bag several times to mix—again, avoid vigorous shaking 1
• The final concentration will be 7.5 mg in 55 mL (approximately 0.136 mg/mL) 1

Administration

• Infuse the entire 55 mL solution intravenously over exactly 30 minutes 1
• Do not administer as an IV push or bolus 1
• Use a dedicated IV line or flush the line with 0.9% sodium chloride before and after rasburicase administration to prevent incompatibilities with other medications 1

Critical Safety Considerations

Contraindications and Warnings

• Absolutely contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as rasburicase causes severe hemolysis and methemoglobinemia in this population 1, 2
• Screen all patients for G6PD deficiency before administration, particularly those of African, Mediterranean, or Southeast Asian descent who have higher prevalence 1, 2
• Discontinue immediately if signs of hemolysis (falling hemoglobin, hemoglobinuria, dark urine) or methemoglobinemia (cyanosis, dyspnea) develop 1

Hypersensitivity Reactions

• Severe hypersensitivity reactions including anaphylaxis, bronchospasm, hypotension, and urticaria can occur at any time during treatment 1, 2
• Have resuscitation equipment and medications (epinephrine, antihistamines, corticosteroids) immediately available during infusion 1
• Monitor patients continuously during the 30-minute infusion and for at least 1 hour afterward 1
• If hypersensitivity occurs, stop the infusion immediately and do not rechallenge 1

Sample Handling for Uric Acid Monitoring

• Blood samples for uric acid measurement must be collected in pre-chilled tubes containing heparin 1
• Immediately immerse samples in an ice water bath 1
• Analyze within 4 hours of collection, as rasburicase continues to degrade uric acid in blood samples at room temperature, producing falsely low values 1
• Failure to follow this protocol will result in inaccurate uric acid measurements that underestimate true serum levels 1

Storage and Handling

• Store unopened vials and diluent ampules at 2°C-8°C (36°F-46°F) 1
• Do not freeze 1
• Protect from light 1
• Once reconstituted and diluted, administer immediately—rasburicase contains no preservatives and is intended for single use only 1
• Discard any unused portion 1

Clinical Context and Efficacy

Expected Response

• Rasburicase produces dramatic reductions in serum uric acid within 4 hours of administration 1, 3
• In the pivotal Phase III trial, 96% of patients achieved uric acid levels ≤2 mg/dL within 4 hours of the first dose 1
• The response rate (uric acid ≤7.5 mg/dL from day 3-7) was 87% with rasburicase compared to 66% with allopurinol alone 1

Alternative Dosing Considerations

• While the FDA-approved regimen is 0.2 mg/kg/day for 5 days, emerging evidence suggests single-dose or weight-based dosing may be effective in select patients 4, 5
• A single 6 mg dose rapidly lowered uric acid in 10 of 11 adults with hematologic malignancies, with median uric acid declining from 11.7 mg/dL to 2.0 mg/dL within 24 hours 5
• However, these alternative regimens are off-label and should only be considered after consultation with oncology/hematology specialists 4, 5
• For the standard FDA-approved indication, use the full 7.5 mg dose as prescribed 1

Common Pitfalls to Avoid

• Never shake the vials vigorously—rasburicase is a recombinant protein enzyme that denatures with excessive agitation 1
• Never mix rasburicase with other medications in the same IV line without flushing first, as compatibility data are limited 1
• Never administer rasburicase without first ruling out G6PD deficiency in at-risk populations—this is a potentially fatal error 1, 2
• Never rely on uric acid measurements from improperly handled samples—room temperature samples will show falsely low values due to continued enzymatic degradation 1
• Never assume the patient can receive additional doses if hypersensitivity occurs—rechallenge is contraindicated 1