The following serious adverse reactions occur with Elspar treatment [See WARNINGS AND PRECAUTIONS]:

• Anaphylaxis and serious allergic reactions
• Serious thrombosis
• Pancreatitis
• Glucose intolerance
• Coagulopathy

The most common adverse reactions with Elspar (asparaginase) 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 (asparaginase) 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 (asparaginase) 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 (asparaginase) . 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.

Central Nervous System effects including coma, seizures, and hallucinations.

Common Adverse Reactions

Azotemia, liver function abnormalities, including hyperbilirubinemia, and elevated transaminases.

Immunogenicity

As with all therapeutic proteins, there is a potential for immuno-genicity, defined as development of binding and/or neutralizing antibodies to the product.

Elspar (asparaginase) 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 (asparaginase) as measured by enzyme-linked immunosorbent assays (ELISA).^{1, 2} Clinical hypersensitivity reactions to Elspar (asparaginase) in studies were common ranging from 32.5%³ to 75%.¹ In these studies, con-comitant medications and dosing schedules varied. Patients with hypersensitivity reactions were more likely to have antibodies than those without hypersensitivity reactions.¹ Hypersensitivity reactions have been associated with increased clearance of Elspar (asparaginase) .⁴ Incidence of antibody formation was lower upon first administration of Elspar (asparaginase) than second administration.^{1, 2} 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.² 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 (asparaginase) with the incidence of antibodies to other products may be misleading.

Read the Elspar (asparaginase) Side Effects Center for a complete guide to possible side effects »

No formal drug interaction studies between Elspar (asparaginase) and other drugs have been performed.

REFERENCES

1.Wang, B.; Relling, M.V.; Storm, M.C.; Woo, M.H.; Ribeiro, R.; Pui, C.H.; Hak, L.J.: Evaluation of immunologic crossreaction of anti-asparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients, Leukemia 17: 1583-1588, 2003.

2. Avramis, V.I.; Sencer, S.; Periclou, A.P.; Sather, H.; Bostrom, B.C.; Cohen, L.J.; Ettinger, A.G.; Ettinger, L.J.; Franklin, J.; Gaynon, P.S.; Hilden, J.M.; Lange, B.; Majlessipour, F.; Mathew, P.; Needle, M.; Neglia, J.; Reaman, G.; Holcenberg, J.S.: A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study, Blood 99:1986-1994, 2002.

3. Woo, M.H.; Hak, L.J.; Storm, M.C.; Sandlund, J.T.; Ribeiro, R.C.; Rivera, G.K.; Rubnitz, J.E.; Harrison, P.L.; Wang, B.; Evans, W.E.; Pui, C.H.; Relling, MV:Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia, J.Clin.Oncol. 18(7): 1525-1532, Apr.2000.

4. Asselin, B.L.: The three asparaginases: Comparative pharmacology and optimal use in childhood leukemia, Adv. Exp. Med. Biol. 457: 621-629, 1999.

Last reviewed on RxList: 10/10/2008
This monograph has been modified to include the generic and brand name in many instances.