Oncaspar

pegaspargase (PEG-L-asparaginase)

Oncaspar

Pharmacologic class: Enzyme

Therapeutic class: Antineoplastic

Pregnancy risk category C

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

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

Avoid inhaling vapors and contact with skin or mucous membranes.

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.

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

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.

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

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.

pegaspargase

(peg-ass-par-jase) ,

Oncaspar

(trade name),

PEG-l-asparaginase

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzymes
Pregnancy Category: C

Indications

Treatment (usually with other agents) of acute lymphoblastic leukemia (ALL) in patients who have had a previous hypersensitivity reaction to native asparaginase.

Action

Consists of l-asparaginase bound to polyethylene glycol (PEG). This compound depletes asparagine, which leukemic cells cannot synthesize. Normal cells are able to produce their own asparagine and are less susceptible to the effects of asparaginase. Binding to PEG renders asparaginase less antigenic and therefore less likely to induce hypersensitivity reactions.

Therapeutic effects

Death of leukemic cells.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Metabolized by serum proteases and in the reticuloendothelial system.
Half-life: 5.7 days (less in patients with previous hypersensitivity to native l-asparaginase).

Time/action profile (hematologic effects)

ROUTEONSETPEAKDURATION
IVrapidunknown14 days

Contraindications/Precautions

Contraindicated in: Pancreatitis or history of pancreatitis;History of previous hemorrhagic reaction to asparaginase therapy;Previous hypersensitivity reactions to pegaspargase.
Use Cautiously in: History of previous hypersensitivity reactions to other drugs;Patients with childbearing potential; Obstetric / Lactation: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • headache
  • malaise

Gastrointestinal

  • pancreatitis (life-threatening)
  • abdominal pain
  • abnormal liver function tests
  • anorexia
  • diarrhea
  • lip edema
  • nausea
  • vomiting

Dermatologic

  • jaundice

Endocrinologic

  • hyperglycemia

Fluid and Electrolyte

  • peripheral edema

Hematologic

  • decreased fibrinogen
  • disseminated intravascular coagulation
  • hemolytic anemia
  • increased thromboplastin
  • leukopenia
  • pancytopenia
  • thrombocytopenia

Local

  • injection site hypersensitivity
  • injection site pain
  • thrombosis

Musculoskeletal

  • arthralgia
  • myalgia
  • pain in extremities

Neurologic

  • paresthesia

Miscellaneous

  • chills
  • hypersensitivity reactions
  • night sweats

Interactions

Drug-Drug interaction

May alter response to anticoagulants or antiplatelet agents.May alter the response to other drugs that are metabolized by the liver.

Route/Dosage

Intramuscular Intravenous (Adults up to 21 yr, and Children with Body Surface Area ≥0.6 m2) 2500 IU/m2 q 14 days (usually in combination with other agents).
Intramuscular Intravenous (Children with Body Surface Area <0.6 m2) 82.5 IU/kg q 14 days (usually in combination with other agents).

Availability

Injection: 750 IU/mL

Nursing implications

Nursing assessment

  • Assess patient for previous hypersensitivity reactions to native l-asparaginase. Monitor for hypersensitivity reaction (urticaria, diaphoresis, facial swelling, joint pain, hypotension, bronchospasm) for at least 1 hr following administration. Epinephrine and resuscitation equipment should be readily available. Reaction may occur up to 2 hr after administration.
  • Monitor for development of bone marrow depression. Assess for fever, sore throat, and signs of infection. Monitor platelet count throughout therapy. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac test stools, urine, and emesis). Avoid giving IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Monitor patient frequently for signs of pancreatitis (nausea, vomiting, abdominal pain).
  • Assess nausea, vomiting, and appetite. Weigh patient weekly. Prophylactic antiemetics may be used prior to administration.
  • Lab Test Considerations: Monitor CBC prior to and periodically throughout therapy. May alter coagulation studies. Fibrinogen may be decreased; PT and partial thromboplastin time (PTT) may be ↑.
    • Monitor serum amylase frequently to detect pancreatitis.
    • Monitor blood glucose; may cause hyperglycemia.
    • May cause elevated BUN and serum creatinine.
    • Hepatotoxicity may be manifested by increased AST, ALT, or bilirubin. Liver function tests usually return to normal after therapy.
    • May cause ↓ serum calcium.
    • May cause elevated serum and urine uric acid and hyponatremia.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • IM is the preferred route because of a lower incidence of adverse reactions.
    • Solutions should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers.
  • Intramuscular: Limit single injection volume to 2 mL. If volume of injection is >2 mL, use multiple injection sites.
  • Intravenous Administration
  • pH: 7.3.
  • Intermittent Infusion: Diluent: Dilute each dose in 100 mL of 0.9% NaCl or D5W. Do not shake or agitate. Do not use if solution is cloudy or has formed a precipitate.
    • Use only 1 dose per vial; do not re-enter the vial. Discard unused portions.
    • Keep refrigerated but do not freeze. Freezing destroys activity but does not change the appearance of pegaspargase.
  • Rate: Administer over 1–2 hr via Y-site through an infusion that is already running.
  • Additive Incompatibility: Information unavailable. Do not admix with other medications or solutions.

Patient/Family Teaching

  • Inform patient of the possibility of hypersensitivity reactions, including anaphylaxis.
  • Advise patient that concurrent use of other medications may increase the risk of bleeding and the toxicity of pegaspargase. Consult health care professional before taking any other medications, including OTC drugs.
  • Instruct patient to notify health care professional if abdominal pain, severe nausea and vomiting, jaundice, fever, chills, sore throat, bleeding or bruising, excess thirst or urination, or mouth sores occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush, electric razor, and to be especially careful to avoid falls. Patients should also be cautioned not to drink alcoholic beverages or take medications containing aspirin or NSAIDs because these may precipitate gastric bleeding.
  • Instruct patient not to receive any vaccinations without advice of health care professional. Advise parents that this may alter child’s immunization schedule.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Improvement of hematologic status in patients with leukemia.
Mentioned in ?
References in periodicals archive ?
Acute Lymphocytic/Lymphoblastic Leukemia (ALL) Therapeutics Market by Drug (Hyper-CVAD Regimen, Linker Regimen, Nucleoside Metabolic Inhibitors, Targeted Drugs & Immunotherapy, CALGB 8811 Regimen, and Oncaspar), and Type (Pediatric and Adult): Global Opportunity Analysis and Industry Forecast, 2019-2026
The franchise included the global rights to ONCASPAR and ex-U.S.
At present, L-asparaginase is available in the market with different brand names, such as ERWINASE, CLOLAR, LEUKINE, ONCASPAR, ARR-ANON, KIDROLASE and ELSPAR.
He has had significant involvement in the development and/or global registration of many drugs including Krystexxa, Onivyde, Oncaspar, Velcade, Alimta, DOXIL and Accolate.
The franchise includes the global rights to ONCASPAR and ex-US and ex-Taiwan rights to ONIVYDE, as well as Oncology pipeline assets.
Shire's Oncology business, which brought in $292 million in revenue in 2017, includes in-market products Oncaspar, Onivyde, and Calaspargase Pegol (Cal-PEG), which is under FDA review for the treatment of acute lymphoblastic leukemia, as well as an early stage immunooncology pipeline.
Shire's Oncology business includes in-market products ONCASPAR, a component of multi-agent treatment for acute lymphoblastic leukemia and ex-U.S.
The medicine, Oncaspar, is primarily sold in the United States, Germany and Poland, and has about $100 million in annual sales, according to Baxter.
There are currently several drugs associated with PEG that are widely traded, including interferon alpha (PEGASYS, PEG-Intron) growth hormone (Somavert), asparaginase (Oncaspar), camptothecin, and insulin, and the PEG has been able to prolong the bioavailability of the drugs [27].
For these reasons, the comparison of the incidence of antibodies to denileukin diftitox with the incidence of antibodies to other products may be misleading' Oncaspar The detection of antibody formation is highly (pegaspargase) 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.
Enzon continues to assist in the development of the next-generation Adagen and Oncaspar programs through a transition services arrangement.