Pegaspargase


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Pegaspargase
(PEG-L-asparaginase)

Pegaspargase (Oncaspar)
PEG-L-asparaginase (Oncaspar)
Pegaspargase
(peg- ASS-pair-gays)
Pregnancy Category: C Oncaspar (Rx)

Classification: Antineoplastic, miscellaneous

See Also: See also Antineoplastic Agents .

Action/Kinetics: Pegaspargase is a modification of the enzyme L-asparaginase. L-asparaginase, derived from Escherichia coli is modified by conjugating covalently units of monomethoxypolyethylene glycol (PEG), thus forming the active PEG-L-asparaginase. Leukemic cells are not able to synthesize asparagine due to a lack of the enzyme asparaginase synthetase and are thus dependent on exogenous asparaginase for survival. Rapid depletion of asparagine, due to administration of asparaginase, kills leukemic cells. Normal cells, which can synthesize their own asparagine, are less affected.

Uses: Clients with acute lymphoblastic leukemia who have developed hypersensitivity to the native forms of L-asparaginase. Used in combination with other antineoplastic drugs, including vincristine, methotrexate, cytarabine, daunorubicin, and doxorubicin. Only use pegaspargase as a single agent when therapy with multiple drugs is determined to be inappropriate for the client.

Contraindications: Pancreatitis or history thereof. Significant hemorrhagic events associated with prior L-asparaginase therapy. Previous allergic reactions, such as generalized urticaria, bronchospasm, laryngeal edema, hypotension, or other side effects to pegaspargase that are not acceptable. Lactation.

Special Concerns: Clients taking pegaspargase are at a higher risk for bleeding problems, especially with simultaneous use of other drugs that have anticoagulant properties (e.g., aspirin, NSAIDs). Safety and efficacy have not been determined in clients from 1 to 21 years of age with known previous hypersensitivity to L-asparaginase.

Side Effects: Most commonly hypersensitivity reactions, chemical hepatotoxicity, and coagulopathies. Allergic reactions: Hypersensitivity reactions (acute or delayed), including life-threatening anaphylaxis may occur during therapy, especially in clients with known hypersensitivity to other forms of L-asparaginase. Also, skin rashes, erythema, edema, pain, fever, chills, urticaria, dyspnea, bronchospasm increased ALT, N&V, malaise, arthralgia, induration, hives, tenderness, swelling, lip edema. GI: Pancreatitis (may be severe), abdominal pain, anorexia, diarrhea, constipation, flatulence, GI pain, indigestion, mucositis, mouth tenderness, severe colitis. Coagulation disorders: Decreased anticoagulant effect, DIC decreased fibrinogen, increased thromboplastin, increased coagulation time, prolonged PTs, prolonged PTTs, clinical hemorrhage (may be fatal) decreased antithrombin III, superficial and deep venous thrombosis, sagittal sinus thrombosis, venous catheter thrombosis, atrial thrombosis, decreased platelet count, purpura, ecchymosis, easy bruisability. Hepatic: Jaundice, abnormal LFTs, liver fatty deposits, hepatomegaly, ascites, liver failure. CV: Hypotension (may be severe), tachycardia, thrombosis, chest pain, hypertension, subacute bacterial endocarditis, edema. Hematologic: Hemolytic anemia leukopenia, pancytopenia, thrombocytopenia, agranulocytosis anemia. CNS: Convulsions, status epilepticus temporal lobe seizures, headache, paresthesia, mild to severe confusion, disorientation, dizziness, emotional lability, somnolence, coma mental status changes, Parkinson-like syndrome. Respiratory: Dyspnea, bronchospasm increased cough, epistaxis, URI. Dermatologic: Injection site hypersensitivity, rash, petechial rash, erythema simplex, pruritus, itching, alopecia, fever blister, hand whiteness, fungal changes, nail whiteness and ridging. GU: Hematuria, increased urinary frequency, abnormal kidney function, severe hemorrhagic cystitis, renal failure uric acid nephropathy. Musculoskeletal: Arthralgia, myalgia, bone pain, joint disorder, diffuse and local musculoskeletal pain, joint stiffness, cramps. Miscellaneous: Pain in the extremities, injection site reaction (including pain, swelling, or redness), night sweats, peripheral edema, increased or decreased appetite, excessive thirst, weight loss, face edema, lesional edema, septic shock, sepsis infection, malaise, fatigue, metabolic acidosis.

Laboratory Test Alterations: AST, amylase, lipase, gamma-glutamyltranspeptidase, BUN, creatinine. Bilirubinemia, hyperglycemia, hyperuricemia, hypoglycemia, hypoproteinemia, hyperammonemia, hyponatremia, hypoalbuminemia, proteinuria.

Drug Interactions: Depletion of serum proteins by pegaspargase may the toxicity of other drugs which are protein bound. Predisposition to bleeding when used with warfarin, heparin, dipyridamole, aspirin, or NSAIDs. May the effect of methotrexate.

How Supplied: Injection: 750 IU/mL

Dosage
?IM (Preferred), IV As a component of selected multidrug regimens.
Adults: 2,500 IU/m 2 q 14 days. This dose is also used if the drug is given as a sole agent. Children with a BSA greater than 0.6 m 2: 2,500 IU/m 2 q 14 days. Children with a BSA less than 0.6 m 2: 82.5 IU/kg q 14 days.

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