The following serious adverse reactions occur with Elspar treatment [see WARNINGS AND PRECAUTIONS]:
- Anaphylaxis and serious allergic reactions
- Serious thrombosis
- Glucose intolerance
- Hepatotoxicity and abnormal liver function
- Posterior Reversible Encephalopathy Syndrome (PRES)
- Risk of Medication Errors
The most common adverse reactions with Elspar are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases.
Clinical Trials and Post-Marketing Experience
The adverse reactions included in this section were identified in single-arm clinical trials in which Elspar was administered as part of a multi-agent regimen or from spontaneous post-marketing reports or published literature.
Because these adverse events were identified in clinical trials that were not designed to isolate the adverse effects of Elspar or were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serious Adverse Reactions
Anaphylaxis and serious allergic reactions. Allergic reactions have occurred with the first dose and with subsequent doses of Elspar. The risk of serious allergic reactions appears to be higher in patients with prior exposure to Elspar or other Escherichia coli-derived L-asparaginases.
Serious thrombosis, including sagittal sinus thrombosis
Pancreatitis, in some cases fulminant or fatal
Glucose intolerance, in some cases irreversible
Coagulopathy, including increased prothrombin time, increased partial thromboplastin time, and decreased fibrinogen, protein C, protein S and antithrombin III. CNS hemorrhages have been reported.
Hepatotoxicity, in some cases fatal, can occur.
Central Nervous System effects including coma, seizures, and hallucinations.
Common Adverse Reactions
Azotemia, liver function abnormalities, including hyperbilirubinemia, and elevated transaminases.
Hyperammonemia, diabetic ketoacidosis, and hyperlipidemia including hypertriglyceridemia and hypercholesterolemia
As with all therapeutic proteins, there is a potential for immunogenicity, defined as development of binding and/or neutralizing antibodies to the product.
Elspar is a bacterial protein and can elicit antibodies in patients treated with the drug. In 2 prospectively designed clinical trials (N=59 and 24), approximately one quarter of the patients developed antibodies that bound to Elspar as measured by enzyme-linked immunosorbent assays (ELISA). Clinical hypersensitivity reactions to Elspar in studies were common ranging from 32.5% to 75%. In these studies, concomitant medications and dosing schedules varied. Patients with hypersensitivity reactions were more likely to have antibodies than those without hypersensitivity reactions. Hypersensitivity reactions have been associated with increased clearance of Elspar. Incidence of antibody formation was lower upon first administration of Elspar than second administration. The frequency of antibody formation in adults relative to children is unknown. There is insufficient information to comment on neutralizing antibodies; however, higher levels of antibody correlated with a decrease in asparaginase activity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications and underlying disease. Therefore, comparison of the incidence of antibodies to Elspar with the incidence of antibodies to other products may be misleading.