Included as part of the "PRECAUTIONS" Section
Grade 3 and 4 hypersensitivity reactions including anaphylaxis have been reported in clinical trials with ASPARLAS with an incidence between 7 to 21% [see CONTRAINDICATIONS , ADVERSE REACTIONS]. Hypersensitivity reactions observed with other asparaginases include angioedema, lip swelling, eye swelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus and rash.
Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administer ASPARLAS in a clinical setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see DOSAGE AND ADMINISTRATION] and observe patients for 1 hour after administration. Discontinue ASPARLAS in patients with serious hypersensitivity reactions.
Cases of pancreatitis have been reported in clinical trials with ASPARLAS with an incidence between 12 to 16% [see ADVERSE REACTIONS]. Hemorrhagic or necrotizing pancreatitis have been reported with other asparaginases.
Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal. Assess serum amylase and/or lipase levels to confirm early signs of pancreatic inflammation. Discontinue ASPARLAS if pancreatitis is suspected; if pancreatitis is confirmed, do not resume ASPARLAS [see DOSAGE AND ADMINISTRATION].
Serious thrombotic events, including sagittal sinus thrombosis, have been reported in clinical trials with ASPARLAS with an incidence of 9 to 12%. Discontinue ASPARLAS in patients experiencing serious thrombotic events [see DOSAGE AND ADMINISTRATION , ADVERSE REACTIONS].
Hemorrhage associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia have been reported in patients receiving ASPARLAS [see ADVERSE REACTIONS]. Evaluate patients with signs and symptoms of hemorrhage with coagulation parameters including PT, PTT, fibrinogen. Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy [see DOSAGE AND ADMINISTRATION].
Hepatotoxicity and abnormal liver function, including elevations of transaminase, bilirubin (direct and indirect), reduced serum albumin, and plasma can occur. Evaluate bilirubin and transaminases at least weekly, during cycles of treatment that include ASPARLAS through at least 6 weeks after the last dose of ASPARLAS. In the event of serious liver toxicity, discontinue treatment with ASPARLAS and provide supportive care [see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , ADVERSE REACTIONS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with calaspargase pegol-mknl.
Use In Specific Populations
There are no available data on the use of ASPARLAS in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Published literature studies in pregnant animals suggest asparagine depletion may cause harm to the animal offspring (see Data). Advise patients of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2%-4% and 15%-20%, respectively.
Animal reproduction studies have not been conducted with ASPARLAS to evaluate its effect on reproduction and fetal development. Published literature studies in which pregnant rabbits were administered L-asparaginase or pregnant rats were deprived of dietary asparagine suggested harm to the animal offspring.
There are no data on the presence of calaspargase pegol-mknl 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 ASPARLAS and for 3 months after the last dose.
Females And Males Of Reproductive Potential
Based on published literature studies in pregnant animals, ASPARLAS can cause fetal harm when administered to a pregnant woman [see Pregnancy].
Conduct pregnancy testing in females of reproductive potential prior to starting treatment with ASPARLAS.
Advise females of reproductive potential to avoid becoming pregnant while receiving ASPARLAS. Females should use effective contraceptive methods, including a barrier method, during treatment and for at least 3 months after the last dose of ASPARLAS. Since there is a potential for an indirect interaction between ASPARLAS and oral contraceptives, the concomitant use of ASPARLAS and oral contraceptives is not recommended. Another, non-oral contraceptive method should be used in women of childbearing potential.
The safety and effectiveness of ASPARLAS in the treatment of ALL have been established in pediatric patients 1 month to < 17 years (no data for the age group < 1 month old). Use of ASPARLAS in these age groups is supported by evidence from an adequate and well-controlled trial with additional safety from a second trial. The trials included 208 children with ALL or lymphoblastic lymphoma treated with ASPARLAS; there were 19 infants (1 month to < 2 years old), 128 children (2 years to < 12 years old), and 61 adolescents (12 years to < 17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups [see ADVERSE REACTIONS , Clinical Studies].