Dosing & Uses
See pediatric dosing
Dosage Forms & Strengths
injectable solution
- 3750 units/5mL (750 units/mL) in single-dose vials
Acute Lymphoblastic Leukemia
Indicated as part of a multiagent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years
Recommended premedication
- Premedicate patients with acetaminophen, an H-1 receptor blocker (such as diphenhydramine), and an H-2 receptor blocker (such as famotidine) 30-60 minutes prior to administration to decrease risk and severity of both infusion and hypersensitivity reactions
<1 month: Safety and efficacy not established
≥1 month: 2500 units/m2 IV no more frequently than every 21 days
Dosage Modifications
Infusion or hypersensitivity reaction
- Grade 1: Reduce infusion rate by 50%
- Grade 2: Interrupt infusion and treat symptoms; when symptoms resolve, resume infusion and reduce rate by 50%
- Grade 3: Discontinue permanently
Hemorrhage
-
Grade 3-4
- Hold dosing
- Evaluate for coagulopathy and consider clotting factor replacement
- Resume dosing with next scheduled dose if bleeding controlled
Pancreatitis
-
Grade 3-4
- Hold dosing for elevated lipase or amylase >3x ULN until enzymes levels stabilize or are declining
- Discontinue permanently if clinical pancreatitis confirmed
Thromboembolism
-
Uncomplicated DVT
- Hold dosing
- Treat with appropriate antithrombotic therapy
- Consider resuming upon resolution of symptoms, while continuing antithrombotic therapy
-
Severe or life-threatening thrombosis
- Discontinue permanently
- Treat with appropriate antithrombotic therapy
Hepatotoxicity
- Total bilirubin >3 to ≤10x ULN: Hold dosing until total bilirubin decreases to ≤1.5x ULN
- Total bilirubin >10x ULN: Discontinue dose and do not make up for missed doses
Dosing Considerations
Verify pregnancy status in females of reproductive potential before initiating
Monitor patients at least weekly, with bilirubin, transaminases, glucose, and clinical examinations until recovery from the therapy cycle
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (5)
- dienogest/estradiol valerate
calaspargase pegol, dienogest/estradiol valerate. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
- drospirenone
calaspargase pegol, drospirenone. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
- ethinylestradiol
calaspargase pegol, ethinylestradiol. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
- levonorgestrel oral
calaspargase pegol, levonorgestrel oral. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
calaspargase pegol, levonorgestrel oral/ethinylestradiol/ferrous bisglycinate. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
Monitor Closely (0)
Minor (0)
Adverse Effects
>10% All Grades
Pancreatitis (12-16%)
Thrombotic events (9-12%)
>10% Grades 3-4
Elevated transaminase (52%)
Hypersensitivity (7-21%)
Increased bilirubin (20%)
Pancreatitis (18%)
Abnormal clotting studies (14%)
1-10% Grades 3-4
Diarrhea (9%)
Embolic and thrombotic events (8%)
Sepsis (5%)
Dyspnea (4%)
Hemorrhages (4%)
Fungal infection (3%)
Pneumonia (3%)
Arrhythmia (2%)
Cardiac failure (2%)
Warnings
Contraindications
History of serious hypersensitivity reactions, including anaphylaxis, to pegylated L-asparaginase
History of serious thrombosis, pancreatitis, or hemorrhagic during previous L-asparaginase therapy
Severe hepatic impairment
Cautions
Also see Dosage Modifications
Pancreatitis reported; inform patients of signs and symptoms, which, if untreated, could be fatal; assess serum amylase and/or lipase levels; discontinue if pancreatitis suspected and permanently discontinue if confirmed
Serious thrombotic events, including sagittal sinus thrombosis, reported; discontinue if thrombotic event occurs
Hemorrhage associated with increased PT, PTT, and hypofibrinogenemia reported; consider appropriate replacement therapy with severe or symptomatic coagulopathy
Hypersensitivity
- Premedicate patients 30-60 min prior to administration of therapy
- Grade 3-4 hypersensitivity, including anaphylaxis, reported
- Symptoms may include angioedema, lip swelling, eye swelling, erythema, decreased blood pressure, bronchospasm, dyspnea, pruritus, or rash
- Because of this risk, administer in clinical setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, oxygen, intravenous steroids, antihistamines) and observe patients for 1 hr after administration
- Discontinue with serious hypersensitivity
Hepatoxicity
- Hepatotoxicity and abnormal liver function, including elevated transaminases, bilirubin, reduced serum albumin, and plasma, can occur
- Evaluate bilirubin and transaminases at least weekly during treatment cycles and through at least 6 weeks after last dose
- Discontinue if serious liver toxicity occurs; provide supportive care
Pregnancy & Lactation
Pregnancy
There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Based on studies in pregnant animals, calaspargase pegol can cause fetal harm when administered to pregnant women
Conduct pregnancy testing in females of reproductive potential before initiating treatment
Animal studies
- Published literature studies in pregnant animals suggest asparagine depletion may cause harm to the animal offspring; advise patients of the potential risk to a fetus
Contraception
- Advise females of reproductive potential to avoid becoming pregnant while receiving calaspargase pegol
- Effective contraceptive methods, including a barrier method, should be used during treatment and for at least 3 months after the last dose
- Since there is a potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use is not recommended
- Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment
Lactation
There are no data on the presence of calaspargase pegol in human milk, the effects on the breastfed child, or the effects on milk production
Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child, advise lactating women not to breastfeed while receiving calaspargase pegol and for 3 months after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Enzyme that catalyzes conversion of the amino acid L-asparagine into aspartic acid and ammonia
The pharmacological effect is thought to be based on selective killing of leukemic cells owing to depletion of plasma L-asparagine; leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize L-asparagine, and therefore depend on an exogenous source of L-asparagine for survival
Absorption
Peak plasma time: 1.17 h
Peak plasma concentration: 1.62 units/mL
AUC, 0-25 days: 16.9 day·unit/mL
AUC 0-infinity: 25.5 day·unit/mL
Distribution
Vd (steady-state): 2.96 L
Elimination
Half-life: 16.1 days
Clearance: 0.147 L/day
Administration
IV Compatibilities
0.9% NaCl
D5W
IV Preparation
Preservative-free solution should appear clear and colorless
Visually inspect solution for particulate matter, cloudiness, or discoloration; if observed, discard vial
Do not administer if vial has been shaken or vigorously agitated, frozen, or stored at room temperature for >48 hr
Dilute calculated dose in 100 mL of 0.9% NaCl or D5W; discard any unused portion in vial(s)
Premedication
Premedicate with acetaminophen, an H-1 receptor blocker (eg, diphenhydramine), and an H-2 receptor blocker (eg, famotidine) 30-60 minutes before administering
IV Administration
Administer in clinical setting with resuscitation equipment and other agents necessary to treat anaphylaxis and observe patients for 1 hr after administration
After dilution, administer immediately into a running IV infusion of either 0.9% NaCl or D5W
Administer over 1 hr
Do not infuse other drugs through the same IV line during administration
Storage
Unopened vials
- Refrigerate at 2-8°C (36-46°F) in the original carton to protect from light
- Do not shake or freeze
- Store at room temperature (15-25°C [59-77°F]) for up to 48 hr
Diluted solution
- May be stored up to 4 hr at room temperature (15-25°C [59-77°F]) OR
- May refrigerate up to 24 hr at 2-8°C (36-46°F)
- Protect from light
- Do not shake
Images
Formulary
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