Rasburicase
Encyclopedia
Rasburicase is a recombinant
version of a urate oxidase
enzyme
that occurs in many mammals but not in humans.
(TLS) in patients receiving chemotherapy
for hematologic
cancer
s such as leukemia
s and lymphoma
s. It is also being investigated for treating severe hyperuricemia from other sources (e.g., gout
and other rheumatologic conditions).
It catalyses the conversion of uric acid
to allantoin
. Allantoin is an inactive metabolite of purine metabolism, and is five to ten times more soluble than uric acid, so renal excretion is more effective. Rasburicase is unique as a treatment and prevention for renal failure associated with TLS in that it catalyses the metabolism of existing uric acid. Other options prevent uric acid formation.
Rasburicase reduces the risk of renal failure and the need for transfusion. Transfusion has been reported as required in 17 to 25% of TLS cases treated with allopurinol
, and 1.4% of cases treated with rasburicase.
However, rasburicase is much more expensive than conventional therapy.
(incidence unknown) and methemoglobinemia
.
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
version of a urate oxidase
Urate oxidase
The enzyme urate oxidase , or uricase or factor-independent urate hydroxylase, catalyzes the oxidation of uric acid to 5-hydroxyisourate:-Structure:...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that occurs in many mammals but not in humans.
Uses
Rasburicase is approved for use by the U.S. Food and Drug Administration (FDA) (and European counterparts) for the prevention and treatment of tumor lysis syndromeTumor lysis syndrome
In medicine , tumor lysis syndrome is a group of metabolic complications that can occur after treatment of cancer, usually lymphomas and leukemias, and sometimes even without treatment...
(TLS) in patients receiving chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
for hematologic
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s such as leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
s and lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s. It is also being investigated for treating severe hyperuricemia from other sources (e.g., gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
and other rheumatologic conditions).
It catalyses the conversion of uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
to allantoin
Allantoin
Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid....
. Allantoin is an inactive metabolite of purine metabolism, and is five to ten times more soluble than uric acid, so renal excretion is more effective. Rasburicase is unique as a treatment and prevention for renal failure associated with TLS in that it catalyses the metabolism of existing uric acid. Other options prevent uric acid formation.
Rasburicase reduces the risk of renal failure and the need for transfusion. Transfusion has been reported as required in 17 to 25% of TLS cases treated with allopurinol
Allopurinol
Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.- Mechanism of action :...
, and 1.4% of cases treated with rasburicase.
However, rasburicase is much more expensive than conventional therapy.
Side effects
Side effects of rasburicase administration can include anaphylaxisAnaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
(incidence unknown) and methemoglobinemia
Methemoglobinemia
Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. The oxygen–hemoglobin...
.
See also
- AllopurinolAllopurinolAllopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.- Mechanism of action :...
is also indicated for TLS to reduce the blood concentration of uric acid. - PegloticasePegloticasePegloticase is a drug for the treatment of severe, treatment-refractory, chronic gout, developed by Savient Pharmaceuticals...
is a pegylated variant of the uricase enzyme which has been approved for the treatment of refractory gout.
External links
- Elitek (Rasburicase) - Official web site of manufacturer.
- Elitek (Rasburicase) Prescribing Information - Official Prescribing Information of manufacturer.
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200736/pdf/bumc0018-0275.pdf - Elitek (Rasburicase)