Oncaspar Warnings, Precautions, Pregnancy, Nursing, Abuse - L-asparaginase

Oncaspar Warnings, Precautions, Pregnancy, Nursing, Abuse - L-asparaginase

WARNINGS

It is recommended that ONCASPAR® be given under the supervision of an individual who is qualified by training and experience to administer cancer chemotherapeutic agents.

Especially in patients with known hypersensitivity to the other forms of L-asparaginase, hypersensitivity reactions to ONCASPAR®, including life-threatening anaphylaxis, may occur during therapy. As a routine precaution, patients should be kept under observation for one hour with resuscitation equipment and other agents necessary to treat anaphylaxis (epinephrine, oxygen, intravenous steroids, etc.) available.

General

This drug may be a contact irritant, and the solution must be handled and administered with care. Gloves are recommended. Inhalation of vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. In case of contact, wash with copious amounts of water for at least 15 minutes. Anaphylactic reactions require the immediate use of epinephrine, oxygen, intravenous steroids, and antihistamines. Patients taking ONCASPAR® are at higher than usual risk for bleeding problems, especially with simultaneous use of other drugs that have anticoagulant properties, such as aspirin, and non-steroidal anti-inflammatories (SEE DRUG INTERACTIONS). ONCASPAR® may have immunosuppressive activity. Therefore, it is possible that use of the drug in patients may predispose the patient to infection. Severe hepatic and central nervous system toxicity following multi-agent chemotherapy that includes ONCASPAR® may occur. Caution appears warranted when treating patients with ONCASPAR® given in combination with hepatotoxic agents, particularly when liver dysfunction is present.

Patients undergoing ONCASPAR® therapy must be carefully monitored and the therapeutic regimen adjusted according to response and toxicity. Physicians using a given treatment regimen incorporating ONCASPAR® should be thoroughly familiar with its benefits and risks.

Information For Patients

Patients should be informed of the possibility of hypersensitivity reactions, including immediate anaphylaxis, to ONCASPAR®. Patients taking ONCASPAR® are at higher than usual risk for bleeding problems. Patients should be instructed that the simultaneous use of ONCASPAR® with other drugs that may increase the risk of bleeding should be avoided (SEE DRUG INTERACTIONS ). ONCASPAR® may affect the ability of the liver to function normally in some patients. Therapy with ONCASPAR® may increase the toxicity of other medications (SEE DRUG INTERACTIONS). ONCASPAR® may have immunosuppressive activity. Therefore, it is possible that use of the drug in patients may predispose the patient to infection. Patients should notify their physicians of any adverse reactions that occur.

Laboratory Tests

A fall in circulating lymphoblasts is often noted after initiating therapy. This may be accompanied by a marked rise in serum uric acid. As a guide to the effects of therapy, the patient's peripheral blood count and bone marrow should be monitored.

Frequent serum amylase determinations should be obtained to detect early evidence of pancreatitis (SEE CONTRAINDICATIONS). Blood sugar should be monitored during therapy with ONCASPAR® because hyperglycemia may occur. When using ONCASPAR® in conjunction with hepatotoxic chemotherapy, patients should be monitored for liver dysfunction.

ONCASPAR® may affect a number of plasma proteins; therefore, monitoring of fibrinogen, PT, and PTT may be indicated.

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 proteins 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenic studies in animals have not been performed with ONCASPAR® nor have studies been performed on impairment of fertility. ONCASPAR® did not exhibit a mutagenic effect when tested against Salmonella typhimurium strains in the Ames assay.

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with ONCASPAR®. It is also not known whether ONCASPAR® can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ONCASPAR® should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether ONCASPAR® is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions due to ONCASPAR® in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.