Pegaspargase (Systemic)


VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): Oncaspar.

Another commonly used name is
PEG- L-asparaginase .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antineoplastic—

Indications

Accepted

Leukemia, acute lymphoblastic (treatment)—Pegaspargase is indicated for patients with acute lymphoblastic leukemia who require L-asparaginase in their treatment regimen, but have developed hypersensitivity to the native forms of L-asparaginase {01} {11} {14} {17} {18} {19}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Pegaspargase is a modified version of the enzyme L-asparaginase {01} {19}. L-asparaginase is modified by covalently conjugating units of monomethoxypolyethylene glycol (PEG), which has a molecular weight of 5000, to the enzyme, forming the active ingredient PEG- L-asparaginase {01} {19}. The L-asparaginase used in the manufacture of pegaspargase is derived from Escherichia coli {01} {19}. Monomethoxypolyethylene glycol covalently linked with L-asparaginase decreases antigenicity and extends the plasma half-life, allowing lower doses and less frequent administration {19}.

Mechanism of action/Effect:

The growth of malignant and normal cells depends on the availability of specific nutrients and cofactors required for protein synthesis {02} {05}. Some nutrients can be synthesized within the cell, whereas others, such as essential amino acids, require exogenous sources {02}. L-asparagine is a nonessential amino acid synthesized by the transamination of L-aspartic acid by a reaction catalyzed by the enzyme L-asparagine synthetase {02}. The ability to synthesize asparagine is notably lacking in malignancies of lymphoid origin {02} {08}; therefore, leukemic cells are dependent on an exogenous source of asparagine for survival {01} {02}. Asparaginase catalyzes the conversion of L-asparagine to aspartic acid and ammonia {02}. The enzyme does not enter cells; instead, it degrades circulating asparagine to aspartic acid, which cannot be converted to asparagine by the leukemic cells {02}. Rapid depletion of asparagine, which results from treatment with the enzyme L-asparaginase, kills the leukemic cells {01}. Normal cells, however, are less affected by the rapid depletion due to their ability to synthesize asparagine {01}. This therapeutic approach is based on a specific metabolic defect in some leukemic cells that do not produce asparagine synthetase {01} {05}.

In animal studies, pegaspargase is more effective than L-asparaginase when administered at the same dose {19}. One unit of pegaspargase was as effective as 5 units of E. coli L-asparaginase in one tumor type and nearly twice as active as L-asparaginase in another tumor type {19}. In studies of animals with non-Hodgkin's lymphoma, pegaspargase in doses of 10 to 30 International Units per kg (IU/kg) was as effective as L-asparaginase 400 IU/kg, and caused fewer side effects {19}.

Half-life:

L-asparaginase levels are detectable for at least 15 days after intravenous treatment with pegaspargase {19}. After a single intramuscular injection of pegaspargase (2500 International Units per square meter of body surface area [IU/m 2]) in children, the half-life was 5.73 days {01} {02} {13} {19} as compared with 1.24 days after E. coli L-asparaginase (25,000 IU/m 2) and 0.65 days after Erwina L-asparaginase (25,000 IU/m 2) {19}.

Among adults treated with pegaspargase 2500 IU/m 2 every 2 weeks, the half-life was 3.24 days in patients previously hypersensitive to L-asparaginase and 5.69 days in nonhypersensitive patients {19}.

Peak serum concentration:

Found in the lymph at about 20% of the concentration in plasma {03}.

Elimination:
    The metabolic fate and method of elimination of pegaspargase are unknown {04}. Little is excreted in the urine {03} {04}. In one study, the results of serum and urine enzyme-linked immunoadsorbent assay (ELISA) suggest that pegaspargase activity and protein are cleared by mechanisms other than urinary excretion {04}. Possible mechanisms that are consistent with the results of this study include proteolysis of the enzyme and/or removal by an organ other than the kidneys {04}. Although previous reports suggest this may not be the case, pegaspargase may be metabolized by the liver, excreted in the bile, or filtered from the plasma by the reticuloendothelial system {04}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients who are allergic to native forms of L-asparaginase may also be allergic to pegaspargase {01} {13}. During clinical trials, approximately 18% of patients experienced hypersensitivity reactions to pegaspargase {13}. Sixty-five percent of the patients who had reactions previously experienced hypersensitivity reaction to Escherichia coli asparaginase {13}. The other 35% had no prior hypersensitivity reaction to native asparaginase {13}. Since these trials included patients who had previous hypersensitivity reactions to the native asparaginase, the possibility exists that cross-sensitivity played a role in the reported reactions {13}. Documentation of cross-sensitivity between E. coli and Erwina asparaginase in leukemic children exists in which 33% of patients experiencing a reaction to E. coli asparaginase also become hypersensitive to Erwina asparaginase {13}. Therefore, this phenomenon should also be considered as a possible factor when reviewing the incidence of reported hypersensitivity reactions to pegaspargase {13}.

Carcinogenicity

Long-term studies in animals have not been done {01}.

Mutagenicity

Pegaspargase did not exhibit a mutagenic effect when tested against Salmonella typhimurium strains in the Ames mutagenicity assay {01}.

Pregnancy/Reproduction
Fertility—
Studies on the effects of pegaspargase on fertility have not been done {01}.

Pregnancy—
Studies have not been done in humans {01}. However, pegaspargase should be avoided during pregnancy {03} unless it is clearly needed {01}.

Studies have not been done in animals {01}.

FDA Pregnancy Category C {01}.

Breast-feeding

It is not known whether pegaspargase is distributed into breast milk {01}. However, because of the potential for serious adverse reactions due to pegaspargase in nursing infants, a decision should be made to either discontinue nursing or discontinue the medication, taking into account the importance of the medication to the welfare of the mother {01}.

Pediatrics

Infants up to 1 year of age—Safety and efficacy have not been established {01}. The safety and efficacy of pegaspargase have been established in pediatric patients 1 year of age and older with known previous hypersensitivity to L-asparaginase {01}. Pediatric patients treated with pegaspargase had a somewhat lower incidence of known L-asparaginase toxicities, except for hypersensitivity reactions, than the adult patients treated with pegaspargase {01} {13} {19}.



Adolescents

The safety and efficacy of pegaspargase have been established in adolescent and young adult patients 21 years of age and younger with known previous hypersensitivity to L-asparaginase {01}.


Geriatrics


No information is available on the relationship of age to the effects of pegaspargase in geriatric patients.


Dental

The leukopenic and thrombocytopenic effects of pegaspargase may result in an increased incidence of certain microbial infections of the mouth, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts have returned to normal {01}. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Anti-inflammatory drugs, nonsteroidal (NSAIDs) or
» Aspirin or
» Dipyridamole or
» Heparin or
» Warfarin    (patients treated with pegaspargase are at increased risk of bleeding complications, especially when administered concomitantly with agents with anticoagulant properties; imbalances in coagulation factors have been noted with the use of pegaspargase, predisposing the patient to bleeding and/or thrombosis; caution should be used when administering any concurrent anticoagulant therapy {01} {02} {19}; it has also been suggested that blood coagulation factor XIII participates in the cross-linking between fibrins and between fibrin and asparaginase {07})


Blood-dyscrasia causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of pegaspargase may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of pegaspargase, if necessary, should be based on blood counts {01})


» Bone marrow depressants, other (see Appendix II )
Radiation therapy    (additive bone marrow depression, including severe dermatitis and/or mucositis, may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Hepatotoxic medications, other (see Appendix II )    (concurrent use may increase the risk of toxicity {01})


Methotrexate    (pegaspargase antagonizes the effects of methotrexate [antifolate] when given before methotrexate administration; however, if pegaspargase is given 24 hours after methotrexate, the action of the antifolate is abbreviated at that point and patients can tolerate large doses of methotrexate {01} {02})


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by pegaspargase therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by pegaspargase therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the pegaspargase therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
» Alanine aminotransferase (ALT [SGPT]) and
» Alkaline phosphatase and
» Amylase, serum and
» Aspartate aminotransferase (AST [SGOT]) and
» Bilirubin, serum concentrations and
» Blood urea nitrogen (BUN) and
» Glucose, serum and
» Uric acid, serum concentrations    (values may be increased {01})


» Prothrombin time    (may be prolonged {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Allergy to pegaspargase{01}{02}{13}
» Bleeding disorders, associated with previous asparaginase therapy    (pegaspargase should not be used in patients who have experienced significant hemorrhagic events associated with prior asparaginase therapy [all preparations] {13})


» Pancreatitis, or history of    (pegaspargase should not be used in patients with active pancreatitis or a history of pancreatitis {01} {13})


Risk-benefit should be considered when the following medical problems exist
» Anticoagulant therapy, or
» Bleeding disorders, history of    (may cause platelet dysfunction and hemorrhage {01} {02} {13})


» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


» Diabetes mellitus    (increased risk of hyperglycemia {13})


» Hepatic function impairment    (impaired metabolism of pegaspargase may result in fatty changes in the liver and liver failure {01} {03} {13})


» Tumor cell infiltration of the bone marrow
» Caution should be used also in patients with inadequate bone marrow reserves due to previous cytotoxic drug or radiation therapy

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Amylase, concentrations, serum    (recommended at periodic intervals throughout therapy to detect early evidence of pancreatitis {01})


Blood counts, complete, including differential and leukocytes and platelet counts and
Glucose, blood, concentrations and
Hepatic function determinations, including serum transaminase and alkaline phosphatase values and bilirubin concentrations    (recommended at periodic intervals throughout therapy {01})




Side/Adverse Effects

Note: In studies, adult patients treated with pegaspargase had a higher incidence of adverse reactions than children {01} {13}. The exception was hypersensitivity reactions, which occurred more frequently in children {01} {13}.
Anaphylactic-type reactions have been described in three cancer patients receiving intravenous pegaspargase administered over 1 hour every 2 weeks {13}. In two of these patients, anaphylaxis occurred after the second (500 International Units per square meter of body surface area [IU/m 2]) and third (2000 IU/m 2) doses, respectively {13}. A sudden disappearance of plasma asparaginase preceded both reactions {13}. Anti-asparaginase antibodies were seen in one of the patients, and this patient previously had developed a mild allergic reaction to the native enzyme {13}. The second patient, who did not possess anti-asparaginase antibodies, had not previously received native asparaginase {13}. The third patient, who developed bronchospasm following the first dose, had not received native asparaginase previously and had normal enzyme levels with no antibodies present {13}. These results suggest that a sudden disappearance of plasma enzyme levels may predispose patients to hypersensitivity reactions during subsequent pegaspargase administration {13}.
Some investigators described significant reduction in plasma asparaginase activity despite continued administration of Escherichia coli asparaginase {13}. The investigators attributed this reduction in enzyme activity to specific immune globulin G (IgG) antibodies (anti- L-asparaginase antibodies) that destroy the enzyme and/or enhance its clearance {13}. This has been referred to as “silent hypersensitivity,” as it can occur prior to, or in the absence of, an observable clinical hypersensitivity reaction {13}.
Hepatotoxicity occurs in most patients to some degree {11}. It is manifested by decreases in serum albumin and serum lipoprotein levels, and increases in liver transaminase levels {11}. Biopsy specimens and autopsies have shown fatty changes in the liver {11}. Liver toxicity can be dose-limiting, but function generally returns to normal after the medication is discontinued {11}.
Neurotoxicity may occur in some patients {11}. L-asparaginase breaks down L-asparagine into aspartic acid and ammonia, and L-glutamine into L-glutamic acid {11}. Central nervous system changes may result from a high level of ammonia in the blood or from a lack of L-asparagine or L-glutamine in the brain {11}. These changes are characterized by confusion and, rarely, stupor, coma, or death {11}. Neurotoxicity is less common in children {11}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Allergic reaction {01}{13}{19}(skin rash)
    
hyperglycemia (blurry vision; dry mouth and skin; fatigue; increased need to urinate; increased hunger or thirst; unexplained weight loss)—requiring insulin therapy{01}{13}{19}
    
liver damage
    
pancreatitis {01}{06}{13}{15}{19}(abdominal or stomach pain; constipation; nausea; vomiting)

Incidence less frequent
    
Anaphylactic reaction {01}{06}{10}{13}{19}(difficulty in breathing or swallowing; hives; itching, especially of hands or feet; reddening of the skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)

Incidence rare
    
Leukopenia, septicemia, thrombocytopenia, or bone marrow depression {01}{06}{13}{19}(black, tarry stools; blood in urine; cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination; pinpoint red spots on skin; unusual bleeding or bruising)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Fever
    
malaise (general feeling of discomfort or illness)
    
nausea and vomiting{01}{06}{13}{19}

Incidence less frequent
    
Anorexia {01}{13}{19}(lack of appetite)
    
arthralgia or myalgia {01}{13}{19}(pain in joints or muscles)
    
convulsions {01}{13}{19}(seizures)
    
hypoglycemia (anxiety; behavior change similar to drunkenness; blurred vision; cold sweats; confusion; cool pale skin; difficulty in concentrating; drowsiness; excessive hunger; fast heartbeat; headache; nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; unusual tiredness or weakness)
    
hypoproteinemia{01}{13}{19}
    
hypotension reaction {01}{13}{19}(severe tiredness or weakness)
    
pain at place of injection {01}{13}{19}
    
tachycardia {01}{06}{13}{19}(fast heartbeat)





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Pegaspargase (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to pegaspargase

Pregnancy—Use is not recommended; women of childbearing age should be advised to avoid pregnancy during treatment





Breast-feeding—Use is not recommended because of the potential for serious adverse effects in nursing infants





Use in children—Safety and efficacy have not been established in infants up to 1 year of age.






Dental—Patients who develop blood dyscrasias may be at increased risk of microbial infections of the mouth, delayed healing, and gingival bleeding
Other medications, especially nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, dipyridamole, heparin, other bone marrow depressants, or warfarin
Other medical problems, especially allergy to pegaspargase; anticoagulant therapy; bleeding disorders associated with previous asparaginase therapy; chickenpox; diabetes mellitus; hepatic function impairment; herpes zoster; history of bleeding disorders; pancreatitis or history of; or tumor cell infiltration of the bone marrow

Proper use of this medication
Caution in taking combination therapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output to aid in excretion of uric acid

Frequency of nausea and vomiting; importance of continuing medication despite stomach upset

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by the physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur
» Possibility of local tissue injury and scarring if infiltration of intravenous solution occurs; telling doctor or nurse right away about redness, pain, or swelling at injection site


Side/adverse effects
Signs of potential side effects, especially allergic reaction, hyperglycemia, liver damage, pancreatitis, anaphylactic reaction, leukopenia, septicemia, thrombocytopenia, and bone marrow depression


General Dosing Information
Hypersensitivity reactions to pegaspargase, including life-threatening anaphylaxis, may occur during therapy {01} {03}. Therefore, appropriate precautions should be taken prior to pegaspargase administration to prevent allergic or other unwanted reactions, especially in patients with known hypersensitivity to the other forms of L-asparaginase {01}. Precautions should include a review of the patient's history regarding possible sensitivity and the ready availability of epinephrine 1:1000, oxygen, intravenous corticosteroids, and other appropriate agents used for control of immediate allergic reactions {01}. All patients should be observed for 1 hour after pegaspargase administration {13} {19}. Delayed hypersensitivity (more than 1 hour after administration) is possible, however, reactions are more likely to occur within 1 hour of administration {13}.

The National Cancer Institute has developed Common Toxicity Criteria that can be used by health care providers to classify the severity of hypersensitivity reactions {13}. These criteria are:    • Grade 1 or mild hypersensitivity reactions (transient rash) {13}.
   • Grade 2 or moderate hypersensitivity reactions (mild bronchospasm) {13}.
   • Grade 3 or severe hypersensitivity reactions (moderate bronchospasm and/or serum sickness) {13}.
   • Grade 4 or life-threatening hypersensitivity reactions (hypotension and/or anaphylaxis) {13}.
Grade 2–4 reactions are considered dose-limiting and require discontinuation of asparaginase therapy {13}.

Pegaspargase should be given under the supervision of an individual who is qualified by training and experience to administer cancer chemotherapeutic agents {01}.

When administered intravenously, a solution of pegaspargase in water for injection or 0.9% sodium chloride injection should be given over a period of 1 to 2 hours in 100 mL of 0.9% sodium chloride injection or 5% dextrose injection, through an infusion that is already running {01} {11}. When pegaspargase is given intramuscularly, no more than 2 mL of a solution in sodium chloride injection should be injected at a single site {01} {03}. If the volume to be administered is greater than 2 mL, multiple injection sites should be used {01}.

As a component of selected multiple agent regimens, the recommended dose of pegaspargase is 2500 International Units per square meter of body surface area (IU/m 2) every 14 days by either the intramuscular or intravenous route of administration {01}. However, the preferred route of administration is the intramuscular route because of the lower incidence of hepatotoxicity, coagulopathy, and gastrointestinal and renal disorders as compared with the intravenous route of administration {01}.

Pegaspargase, like native L-asparaginase, is used generally in combination with other chemotherapeutic agents, such as vincristine, methotrexate, cytarabine, daunorubicin, and doxorubicin {01} {19}. Multidrug chemotherapy now can cure about 70% of children and about 40% of adults with acute lymphoblastic leukemia {12}. The usual drugs of choice for initial treatment (“induction”) are vincristine, prednisone, and asparaginase with or without daunorubicin or doxorubicin, which produce a remission in more than 95% of children and about 75% of adults {12}.

The use of pegaspargase as the sole induction agent should be undertaken only in an unusual situation in which a combined regimen, using other chemotherapeutic agents such as vincristine, methotrexate, cytarabine, daunorubicin, or doxorubicin, is inappropriate because of toxicity or other specific patient-related factors, or in patients refractory to other therapy {01} {19}. When pegaspargase is to be used as the sole induction agent, the recommended dosage regimen is also 2500 IU/m 2 every 14 days {01}.

Recurrence of childhood acute lymphoblastic leukemia occurs in about 30 to 50% of patients and indicates irresistible progression of the disease {09}. While systemic (i.e., hematologic) relapse is due to drug resistance of leukemic cells, pharmacologic barriers may be responsible for local relapses such as meningeal involvement, leukemic ophthalmopathy or testicular infiltration {09}. L-asparaginase seems to be an important component of drug combinations for reinduction therapy for systemic relapse {09}. Following reinduction therapy, modification of continuation therapy is necessary {09}.

Local relapses require local treatment, i.e., radiotherapy and intrathecal administration of chemotherapy {09}. Local relapse is almost always followed by hematologic relapse; therefore, intensification of systemic therapy is also recommended {09}. Prevention of these relapses is much more important and probably more successful than treatment {09}.

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastic agents may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.

Pegaspargase may be a contact irritant, and therefore the solution must be handled and administered with care {01}. Gloves are recommended. Inhalation of vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided {01}.

For treatment of adverse effects
Recommended treatment consists of the following:
   • For mild hypersensitivity reaction—Administering antihistamines, and, if necessary, corticosteroids {01} {16}.
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines or corticosteroids may also be administered as required {01} {16}.


Parenteral Dosage Forms

PEGASPARGASE INJECTION

Usual adult and adolescent dose
Leukemia, acute lymphoblastic (treatment)
Adults and adolescents up to 21 years of age: Intramuscular or intravenous, 2500 International Units per square meter of body surface area administered every fourteen days {01}.

Adults 21 years of age and older: Safety and efficacy have not been established {01}.


Usual pediatric dose
Leukemia, acute lymphoblastic (treatment)
Infants up to 1 year of age: Safety and efficacy have not been established.

Children with body surface area ³ 0.6 square meter: Intramuscular or intravenous, 2500 International Units per square meter of body surface area administered every fourteen days {01}.

Children with body surface area < 0.6 square meter: Intramuscular or intravenous, 82.5 International Units per kg of body weight administered every fourteen days {01}.


Note: The safety and efficacy of pegaspargase have been established only in patients with known previous hypersensitivity to L-asparaginase who ranged in age from 1 to 21 {01}. Pegaspargase can be administered by intramuscular injection or intravenous infusion in these patients {01} {11}. However, the preferred route of administration is intramuscular injection because of decreased incidence of hypersensitivity reactions {01} {11}.


Strength(s) usually available
U.S.—


750 International Units (IU) per 5-mL vial (Rx) [Oncaspar]{01}

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF), unless otherwise specified by the manufacturer. Protect from freezing {01} {11}.

Stability:
Storage above or below the recommended temperature may reduce potency {01}. Freezing destroys potency, and product should be discarded if freezing occurs {01} {11}.
   • Use only one dose per vial; do not re-enter the vial. Discard unused portions {01}. Do not save unused drug for later administration {01}.
   • Do not use if cloudy or if precipitate is present {01}.
   • Do not use if stored at room temperature for more than 48 hours {01} {11}.

Auxiliary labeling:
   • Avoid excessive agitation {01} {11}. Do not shake {01} {11}.
   • Do not freeze; discard if freezing occurs {01} {11}.



Developed: 08/29/1997
Revised: 07/01/1998



References
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  1. Mutz ID. Prevention of recurrence of childhood acute lymphoblastic leukemia. Onkologie 1978; 1: 35-40.
  1. Ho DH, Brown NS, Yen A, et al. Clinical pharmacology of polyethylene glycol- L-asparaginase. Drug Metab Dispos 1986; 14(3): 349-52.
  1. Ettinger AR. Pharmacology: pegaspargase (Oncaspar). J Pediatr Oncol Nurs 1995; 12(1): 46-8.
  1. Pegaspargase for acute lymphoblastic leukemia. Med Lett Drugs Ther 1995; 37: 23-4.
  1. Alfieri DR. Pegaspargase. Pediatr Nurs 1995; 21(5): 471-4.
  1. Capizzi RL. Asparaginase revisited. Leuk Lymphoma 1993; 10(Suppl): 147-50.
  1. Keating MJ, Holmes R, Lerner S, et al. L-asparaginase and PEG asparaginase—past, present, future. Leuk Lymphoma 1993; 10(Suppl): 153-7.
  1. Fisher M. Treatment of acute anaphylaxis. BMJ 1995; 311: 731-3.
  1. Park YK, Abuchowski A, Davis S, et al. Pharmacology of Escherichia coli- L-asparaginase polyethylene glycol adduct. Anticancer Res 1981; 1: 373-6.
  1. Kawashima K, Takeshima H, Higashi Y, et al. Case report: high efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies. Leuk Res 1991; 15(6): 525-30.
  1. Levien TL, Baker DE. Reviews of pegaspargase and oral pilocarpine. Hosp Pharm 1995; 30(1): 52, 54-6.
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