pegaspargase

Action

Stimulates production of effector proteins, such as serum neopterin and 2', 5' oligodenylate synthetase; raises body temperature and reversibly lowers white blood cell and platelet counts

Availability

Injection: 750 international units/ml, 5-ml vial in phosphate-buffered saline solution

Indications and dosages

➣ Acute lymphoblastic leukemia

Adults and children with body surface area (BSA) greater than 0.6 m²: 2,500 international units/m² I.M. or I.V. q 14 days

Adults and children with BSA less than 0.6 m²: 82.5 international units/m² I.M. or I.V. q 14 days

Contraindications

• Hypersensitivity or previous serious allergic reaction (such as generalized urticaria, bronchospasm, laryngeal edema, hypotension) to drug

• Pancreatitis or history of pancreatitis

• Previous hemorrhagic events related to L-asparaginase therapy

Precautions

Use cautiously in:

• renal or hepatic disease, CNS disorders

• concurrent use of hepatotoxic agents, anticoagulants, aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)

• pregnant or breastfeeding patients.

Administration

See Follow facility protocol for handling, preparing, and disposing of chemotherapeutic drugs.

See Avoid inhaling vapors and contact with skin or mucous membranes.

See Keep resuscitation equipment, epinephrine, oxygen, steroids, and anti-histamines readily available.

• Know that I.M. route is preferred because it's less likely to cause hepato-toxicity, coagulopathy, and GI or renal disorders. For single I.M. injection, don't exceed volume of 2 ml.

• For I.V. use, dilute in 100 ml of normal saline solution or dextrose 5% in water. Infuse over 1 to 2 hours.

See Don't freeze; freezing inactivates drug.

Adverse reactions

CNS: dizziness, headache, confusion, hallucinations, emotional lability, drowsiness, neuritis, Parkinson-like syndrome, malaise, coma, seizures

CV: hypertension, hypotension, chest pain, peripheral edema, tachycardia, endocarditis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, anorexia, pancreatitis GU: glycosuria, polyuria, urinary frequency, hematuria

Hematologic: hemolytic anemia, leukopenia, pancytopenia, thrombocy-topenia, disseminated intravascular coagulation

Hepatic: jaundice, fatty liver deposits, hepatotoxicity, hepatomegaly

Metabolic: hypoproteinemia, hyperuricemia, hyperammonemia, hyponatremia, hyperglycemia, hypoglycemia Respiratory: dyspnea, cough, bronchospasm

Skin: rash, urticaria, pruritus, night sweats, alopecia

Other: increased appetite and thirst, weight loss, chills, fever, injection site reaction, facial or lip edema, hypersensitivity reactions including anaphylaxis, septic shock

Interactions

Drug-drug. Aspirin, dipyridamole, heparin, NSAIDs, warfarin: increased risk of bleeding or thrombosis

Methotrexate: decreased methotrexate action

Drug-diagnostic tests. Amylase, blood urea nitrogen, creatinine, lipase, uric acid: increased levels

Glucose: increased or decreased level

Liver function tests: abnormal results

Lymphoblasts: decreased count

Plasma proteins: altered levels

Patient monitoring

See Watch for anaphylaxis and other hypersensitivity reactions, especially during first hour of therapy.

• Monitor CBC (including platelet count); fibrinogen; prothrombin and partial thromboplastin times; International Normalized Ratio; and serum amylase, lipase, and uric acid levels.

See Assess neurologic status. Stay alert for decreased level of consciousness and evidence of impending seizure.

• Check for signs and symptoms of bleeding, infection, and hyperglycemia.

• Monitor heart rate, blood pressure, respiratory rate, temperature, and fluid intake and output.

Patient teaching

See Teach patient to recognize and immediately report signs and symptoms of hypersensitivity reactions, bleeding, infection, and other adverse reactions.

• Tell patient drug is likely to cause reversible hair loss.

• Stress importance of undergoing follow-up laboratory tests.

• Advise patient to avoid situations that increase risk for infection.

• Instruct patient to consult pre-scriber before taking other prescription drugs or over-the-counter preparations.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.