Oncaspar (Pegaspargase) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Unfavorable interactions of L-asparaginase with some antitumor agents have been demonstrated. ¹ It is recommended, therefore, that ONCASPAR® be used in combination regimens only by physicians familiar with the benefits and risks of a given regimen. Depletion of serum protein by ONCASPAR® may increase the toxicity of other drugs which are protein bound. Additionally, during the period of its inhibition of protein synthesis and cell replication, ONCASPAR® may interfere with the action of drugs such as methotrexate, which require cell replication for their lethal effects. ONCASPAR® may interfere with the enzymatic detoxification of other drugs, particularly in the liver. Physicians using a given treatment regimen should be thoroughly familiar with its benefits and risks.

Imbalances in coagulation factors have been noted with the use of ONCASPAR® predisposing to bleeding and/or thrombosis. Caution should be used when administering any concurrent anticoagulant therapy, such as coumadin, heparin, dipyridamole, aspirin, or non-steroidal anti-inflammatories.

OVERDOSAGE

Three patients received 10,000 IU/m² of ONCASPAR® as an intravenous infusion. One patient experienced a slight increase in liver enzymes. A second patient developed a rash ten minutes after the start of the infusion, which was controlled with the administration of an antihistamine and by slowing down the infusion rate. A third patient did not experience any adverse reactions.

CONTRAINDICATIONS

ONCASPAR® is contraindicated in patients with pancreatitis or a history of pancreatitis. ONCASPAR® is contraindicated in patients who have had significant hemorrhagic events associated with prior L-asparaginase therapy. ONCASPAR® is also contraindicated in patients who have had previous serious allergic reactions, such as generalized urticaria, bronchospasm, laryngeal edema, hypotension, or other unacceptable adverse reactions to ONCASPAR®.

REFERENCES

1. Capizzi, RL and Holcenberg, JS. Asparaginase. In: Holland and Frei (eds). Cancer Med third edition, Lea and Febiger, Phila. PA, 1993.
2. Ho, DH, et al. Clinical pharmacology of polyethylene glycol-L-asparaginase. Drug Metab Dispos 14 (3): 349-352, 1986.
3. Asselin, BL, et al. Comparative Pharmacokinetic Studies of Three L-asparaginase Preparations. J Clin Oncology (11): 1780-1786, 1993.
4. Data on File at ENZON.
5. Clavell, LA, et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med 315 (11): 657-663, 1986.

ENZON Pharmaceuticals, Inc.

20 Kingsbridge Road

Piscataway, NJ 08854 USA PN 200-030A