Calaspargase pegol

Indications

Calaspargase pegol is used for: Acute Lymphoblastic Leukemia

Adult Dose

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 <21 years: 2500 units/m² IV no more frequently than every 21 days

Child Dose

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 <1 month: Safety and efficacy not established >1 month: 2500 units/m² IV no more frequently than every 21 days

Renal Dose

Administration

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) 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

Contra Indications

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

Precautions

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 in increased PT, PTT, and hypofibrinogenemia reported; consider appropriate replacement therapy with severe or symptomatic coagulopathy

Pregnancy-Lactation

Pregnancy 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 Another, nonoral contraceptive method should be used in women of childbearing potential 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

Interactions

Side Effects

Side effects of Calaspargase pegol : >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%)

Mode 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