ELITEK (rasburicase) Safety
The Safety of ELITEK (rasburicase) Was Studied in Both Adult and Pediatric Patients (N = 887)
Among the 347 (265 pediatric; 82 adult) patients for whom all adverse reactions regardless
of severity were assessed in Studies 1, 2 and 3, as well as an uncontrolled safety
trial, the most frequently observed adverse reactions (incidence ≥10%) were vomiting
(50%), fever (46%), nausea (27%), headache (26%), abdominal pain (20%), constipation
(20%), diarrhea (20%), mucositis (15%), and rash (13%).
Among the 275 adult patients in Study 4, hypersensitivity reactions occurred in
4.3% of patients treated with ELITEK alone and 1.1% of patients treated with
the ELITEK/oral allopurinol combination. Hypersensitivity reactions included
arthralgia, injection site irritation, peripheral edema, and rash. The most common
Grade 3 or 4 adverse reactions regardless of relationship to study drug in the 3
arms of Study 4 (ELITEK alone; ELITEK combined with oral allopurinol;
oral allopurinol alone) were sepsis (5.4%; 6.5%; 4.4%), hypophosphatemia (4.3%;
6.5%; 6.6%), anxiety (3.3%; 0%; 0%), abdominal pain (3.3%; 4.3%; 2.2%), hyperbilirubinemia
(3.3%; 2.2%; 4.4%), and increased alanine aminotransferase (3.3%; 4.3%; 2.2%), respectively.
The following serious adverse reactions occurred with a difference in incidence
of greater than or equal to 2% in patients receiving ELITEK compared to patients
receiving oral allopurinol in randomized studies
(Study 1 and Study 4): pulmonary
hemorrhage, respiratory failure, supraventricular arrhythmias, ischemic coronary
artery disorders, and abdominal and gastrointestinal infections.
Adult Study: Percent Incidence of Selected Grade 3/4 Adverse Reactions By Study
Arm2
|
Adverse Reaction*
|
ELITEK
(n = 92)
|
ELITEK/Allopurinol
(n = 92)
|
Allopurinol
(n = 92)
|
|
Nausea
|
1.1
|
1.1
|
2.2
|
|
Peripheral edema
|
2.2
|
3.3
|
6.6
|
|
Vomiting
|
1.1
|
0
|
1.1
|
|
Anxiety
|
3.3
|
0
|
0
|
|
Abdominal pain
|
3.3
|
4.3
|
2.2
|
|
Hypophosphatemia
|
4.3
|
6.5
|
6.6
|
|
Hyperbilirubinemia
|
3.3
|
2.2
|
4.4
|
|
Pharyngolaryngeal pain
|
1.1
|
0
|
0
|
|
Sepsis
|
5.4
|
6.5
|
4.4
|
|
Fluid overload
|
0
|
0
|
1.1
|
|
Increased alanine aminotransferase
|
3.3
|
4.3
|
2.2
|
|
Hyperphosphatemia
|
0
|
0
|
1.1
|
*Events were reported and graded according to NCI-CTC Version 3.0 and presented
as preferred terms MedDRA version 10.1. Overall incidence ≥10% in any ELITEK
arm and the difference between any ELITEK arm versus the allopurinol arm
≥5%.
- The incidence of anaphylaxis hemolysis and methemoglobinemia was <1% of the 887
ELITEK-treated patients enrolled in these clinical trials.2
- The following serious adverse reactions occurred at a difference in incidence of
≥2% in patients receiving ELITEK compared to patients receiving allopurinol
in randomized studies: pulmonary hemorrhage, respiratory failure, supraventricular
arrhythmias, ischemic coronary artery disorders, and abdominal and gastrointestinal
infections.2
- Hypersensitivity reactions occurred in 4.3% of ELITEK-treated patients and 1.1% of
ELITEK/allopurinol-treated patients. Clinical manifestations of hypersensitivity
included arthralgia, injection site irritation, peripheral edema, and rash.2
No Metabolic-Based Drug Interactions or Dose Reductions When Administered With Cytotoxic
Medications2
- No studies of interactions with other drugs have been conducted in humans.
- ELITEK does not metabolize allopurinol, cytarabine, methylprednisolone, methotrexate,
6-mercaptopurine, thioguanine, etoposide, daunorubicin, cyclophosphamide, or vincristine
in vitro. No metabolic-based drug interactions are therefore anticipated with these
agents in patients.
- ELITEK does not affect the activity of isoenzymes CYP1A, CYP2A, CYP2B, CYP2C,
CYP2E, and CYP3A in vivo, suggesting no induction or inhibition potential. Clinically
relevant P450-mediated drug-drug interactions are therefore not anticipated in patients
based on the recommended dosing schedule.
- ELITEK is contraindicated in individuals deficient in glucose-6-phosphate
dehydrogenase (G6PD) (see BOXED WARNINGS). ELITEK is contraindicated
in patients with a known history of anaphylaxis or hypersensitivity reactions, hemolytic
reactions, or methemoglobinemia reactions to ELITEK or any of the excipients
(see BOXED WARNINGS).
- It is recommended that patients at higher risk for G6PD deficiency (eg, patients
of African or Mediterranean ancestry) be screened prior to starting ELITEK
therapy (see BOXED WARNINGS, Hemolysis).
- ELITEK administration should be immediately and permanently discontinued
in any patient developing clinical evidence of a serious hypersensitivity reaction,
hemolysis, or methemoglobinemia, and appropriate patient monitoring and support
measures should be implemented (see BOXED WARNINGS). The safety
and efficacy of ELITEK have been established only for a single course of
treatment (once daily for 5 days).
- ELITEK requires special sample handling. Uric acid must be analyzed in plasma.
Blood must be collected into prechilled tubes containing heparin anticoagulant.
Samples must be immediately immersed in an ice water bath. Plasma
samples must be prepared by centrifugation in a precooled centrifuge (4˚C). Finally,
the plasma must be maintained in an ice water bath and analyzed for uric acid within
4 hours of collection (see BOXED WARNINGS, Interference With Uric Acid Measurements).