Rasburicase – Uses, Dosage, Side Effects, Interaction

Rasburicase is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans.^[1] Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.^[rx]

Mechanism of action

Rasburicase catalyzes the enzymatic oxidation of uric acid into an inactive and soluble metabolite (allantoin).

Rasburicase (Q00511) is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent. Elitek (rasburicase) is supplied in 3 mL and 10 mL colorless, glass vials containing rasburicase at a concentration of 1.5 mg/mL after reconstitution.^[2]

Rasburicase injection is used to treat high levels of uric acid (a natural substance that builds up in the blood as tumors break down) in people with certain types of cancer who are being treated with chemotherapy medications. Rasburicase injection is in a class of medications called enzymes. It works by breaking down uric acid so that the body can eliminate it.

Indications

• Drugs used to treat lymphoid leukemia?, non-Hodgkin’s lymphoma and acute? myelogenous leukemia often lead to the accumulation of toxic plasma levels of purine metabolites (i.e. uric acid). The injection of rasburicase reduces levels of uric acid and mitigates the toxic effects of chemotherapy-induced tumor? lysis.
• The initial management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving chemotherapy is expected to result in tumor lysis and subsequent elevation of plasma uric acid.
• For treatment of hyperuricemia, reduces elevated plasma uric acid levels (from chemotherapy)
• Hyperuricemia
• Rasburicase is approved for use by the U.S. Food and Drug Administration (and European counterparts) for the prevention and treatment of tumor lysis syndrome? (TLS)^[rx] in people receiving chemotherapy for hematologic cancers such as leukemias and lymphomas. However, it is not clear if it results in important benefits such as decreased kidney? problems or decreased risk of death as of 2017.^[rx]
• It is being investigated for treating severely high blood levels of uric acid from other sources. For example, it has been used for hyperuricemia in gout,^[rx] in other rheumatologic conditions, and in rhabdomyolysis with kidney failure?.^[rx]

Use in Cancer

Leuprolide acetate is approved for palliative treatment of:

• Prostate cancer that is advanced.

Leuprolide acetate is also being studied in the treatment of other types of cancer.

Contraindications

Rasburicase is contraindicated? in patients who are glucose-6-phosphate dehydrogenase deficient because these patients cannot break down hydrogen peroxide, a byproduct of rasburicase, which can lead to hemolysis

• glucose-6-phosphate dehydrogenase (G6PD) deficiency
• destruction of red blood cells
• methemoglobinemia, a type of blood disorder
• a patient who is producing milk and breastfeeding
• anemia? from pyruvate kinase and G6PD deficiencies

Dosage?

Strengths: 1.5 mg; 7.5 mg

Hyperuricemia Secondary to Chemotherapy

• 0.2 mg/kg as a 30-minute IV infusion once a day for up to 5 days
• Use beyond 5 days or administration of more than 1 course of therapy is not recommended
• The exact duration should be based upon adequate monitoring? of uric acid levels in plasma and clinical? judgement.
• This drug is only approved for a single course of treatment.

Pediatric Dose for Hyperuricemia Secondary to Chemotherapy

• 0.2 mg/kg as a 30-minute IV infusion once a day for up to 5 days
• Use beyond 5 days or administration of more than 1 course of therapy is not recommended.
• The exact duration should be based upon adequate monitoring of uric acid levels in plasma and clinical judgment.
• This drug is only approved for a single course of treatment.

HYPERSENSITIVITY REACTIONS:

• This drug can cause serious and fatal hypersensitivity reactions, including anaphylaxis?.
• Immediately and permanently discontinue this drug in patients who experience a serious hypersensitivity reaction

HEMOLYSIS:

• Do not administer to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Immediately and permanently discontinue this drug in patients developing hemolysis.
• Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting treatment.

METHEMOGLOBINEMIA:

• This drug can result in methemoglobinemia in some patients.
• Immediately and permanently discontinue this drug in patients developing methemoglobinemia.

INTERFERENCE WITH URIC ACID MEASUREMENTS:

• This drug enzymatically degrades uric acid in blood samples left at room temperature.
• Collect blood samples in pre-chilled tubes containing heparin and immediately immerse and maintain the sample in an ice water bath.
• Assay plasma samples within 4 hours of collection.

Administration advice:

• Administer by IV infusion; do not give by IV bolus injection.
• Infuse over 30 minutes through a separate line or flush line with at least 15 mL of normal saline prior to and after administration.
• Do not use filters during infusion.

Side Effects

The Most Common

• nausea?
• vomiting?
• constipation?
• diarrhea?
• stomach pain?
• mouth sores
• throat pain?
• fever?
• headache?
• anxiety
• join pain?
• swelling? of the hands, feet, ankles, or lower legs
• pain, redness, swelling, or tenderness? at the injection site

More common

• Cracked lips
• diarrhea
• difficulty with swallowing
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• Abdominal or stomach pain
• agitation
• black or red, tarry, stools
• bleeding gums
• bluish color of the fingernails, lips, skin, palms, or nail beds
• changes in skin color
• changes in vision
• chest pain? or discomfort
• chills?
• coma
• confusion
• convulsions (seizures)
• cough
• coughing that sometimes produces a pink, frothy sputum
• coughing up blood
• decreased urination
• depression
• dilated neck veins
• dizziness
• dry mouth
• fainting
• fast, slow, or irregular heartbeat
• fever
• headache
• hostility
• increased menstrual flow or vaginal bleeding
• increased sweating
• increased thirst
• irritability
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• lightheadedness
• lower back or side pain
• muscle twitching
• nausea
• no blood pressure or pulse
• nosebleeds
• pain or discomfort in the arms, jaw, back, or neck
• pain, tenderness, or swelling of the foot or leg
• painful or difficult urination
• pains in the chest, groin, or legs, especially calves of the legs
• pale skin
• paralysis
• prolonged bleeding from cuts
• red or dark brown urine
• severe constipation
• severe headaches of sudden onset
• shortness of breath
• skin rash
• sneezing
• sore throat
• stopping of heart
• stupor
• sudden loss of coordination
• sudden onset of shortness of breath for no apparent reason
• sudden onset of slurred speech
• sunken eyes
• sweating
• swelling of the face, fingers, feet, or lower legs
• swollen glands
• temporary blindness
• thirst
• tightness in the chest
• troubled breathing
• unconsciousness
• unexplained or unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weight gain
• wheezing
• wrinkled skin

Rare

• Back pain
• hives
• itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
• yellow eyes or skin
• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• feeling of warmth
• feeling unusually cold
• redness of the face, neck, arms, and occasionally, upper chest
• shivering

Interactions

Pregnancy and Lactation

FDA Pregnancy Category C

Pregnancy

There are no studies of rasburicase in pregnant women. Reproductive toxicity studies in rabbits treated during organogenesis with approximately 10 to 100 times the recommended human dose of rasburicase resulted in teratogenicity, including decreased fetal body weights and heart and great vessel malformations at all dose levels. Multiple hearts and great vessel malformations
were also observed in the offspring of pregnant rats treated with approximately 250 times the recommended human dose of rasburicase. Other adverse effects were observed in rasburicase-treated pregnant rabbits at all dose levels tested and included pre-and post-implantation losses, abortions, and decreased uterine weights. It is unknown whether rasburicase can cross the placental barrier in humans and result in fetal harm. Because of the observed teratogenic effects of rasburicase in animal reproductive studies, use rasburicase during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Lactation

It is not known whether rasburicase is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from rasburicase, a decision should be made whether to discontinue nursing or to discontinue rasburicase, taking into account the importance of the drug to the mother.

References