pegaspargase

High Alert

First-line treatment of acute lymphoblastic leukemia (ALL) (in combination with other chemotherapy agents).
ALL in patients who have had a previous hypersensitivity reaction to native l-asparaginase (in combination with other chemotherapy agents).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to pegaspargase;
History of serious thrombosis with previous l-asparaginase therapy;
History of pancreatitis, including pancreatitis association with previous l-asparaginase therapy;
History of serious hemorrhagic events to previous l-asparaginase therapy;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of previous hypersensitivity reaction to l-asparaginase (↑ risk of hypersensitivity reaction);
Rep: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DEEP VEIN THROMBOSIS (DVT), peripheral edema

Endo: hyperglycemia

GI: abdominal pain, anorexia, diarrhea, HEPATOTOXICITY(INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE), nausea, PANCREATITIS, vomiting

Hemat: HEMORRHAGE, neutropenia

Local: injection site reactions

Metab: hypercholesterolemia, hypertriglyceridemia

MS: arthralgia, myalgia

Neuro: headache, malaise, paresthesia, SEIZURES

Resp: PULMONARY EMBOLISM

Misc: chills, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), night sweats

Interactions ⬆ ⬇

Drug-drug:

May alter response to anticoagulants or antiplatelet agents.
May ↑ risk of toxicity of dexamethasone.

Availability ⬆ ⬇

Solution for injection: 750 units/mL

Route/Dosage ⬆ ⬇

IM IV (Adults >21 yr): 2500 units/m² no more frequently than every 14 days.
IM IV (Adults and Children ≤21 yr): 2000 units/m² no more frequently than every 14 days.

US Brand Names ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzymes

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	unknown	14 days

Patient/Family Teaching ⬆ ⬇

Inform patient of the possibility of hypersensitivity reactions, including anaphylaxis.
Advise patient that concurrent use of other medications may ↑ 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 and electric razor and to be especially careful to avoid falls. Advise patient 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.
Rep: May cause fetal harm. Advise females of reproductive potential to use two methods of effective contraception, including a barrier method, for ≥3 mo after last dose. Advise females to avoid breastfeeding during therapy and for ≥1 mo after last dose. Pegaspargase may ↓ effectiveness of hormonal contraceptives; hormonal contraceptives are not recommended.
Emphasize the need for periodic lab tests to monitor for side effects.

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Indications ⬇