ered L-asparaginase or pregnant rats were deprived of dietary asparagine suggested harm to theanimal offspring.
8.2 Lactation
Risk Summary
There are no data on the presence of calaspargase pegol-mknl in human milk, the effects on thebreastfed child, or the effects on milk production. Because many drugs are excreted in human milk andbecause of the potential for adverse reactions in a breastfed child, advise lactating women not to breastfeedwhile receiving ASPARLAS and for 3 months after the last dose.
8.3 Females and Males of Reproductive Potential
Based on published literature studies in pregnant animals, ASPARLAS can cause fetal harm whenadministered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy TestingConduct pregnancy testing in females of reproductive potential prior to starting treatment with
ASPARLAS.
Contraception
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 forat least 3 months after the last dose of ASPARLAS. Since there is a potential for an indirect interactionbetween ASPARLAS and oral contraceptives, the concomitant use of ASPARLAS and oral contraceptivesis not recommended. Another, non-oral contraceptive method should be used in women of childbearingpotential.
8.4 Pediatric Use
The safety and effectiveness of ASPARLAS in the treatment of ALL have been established inpediatric patients 1 month to < 17 years (no data for the age group < 1 month old).
Use of ASPARLAS inthese age groups is supported by evidence from an adequate and well-controlled trial with additional safetyfrom a second trial. The trialsincluded 208 children with ALL or lymphoblastic lymphoma treated withASPARLAS; 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 ornadir serum asparaginase activity across age groups [see Adverse reactions (6.1), Clinical Studies (14)].
11 DESCRIPTION
Calaspargase pegol-mknl contains an asparagine specific enzyme derived from Escherichia coli, asa conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol(mPEG) with a succinimidyl carbonate (SC) linker. The SC linker is a chemically stable carbamate bondbetween the mPEG moiety and the lysine groups of L-asparaginase.
L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists ofidentical 34.5 kDa subunits. Approximately 31 to 39 molecules of SC-PEG are linked to L-asparaginase;
the molecular weight of each SC-PEG molecule is about 5 kDa. The activity of ASPARLAS is expressed inunits (U).
ASPARLAS injection is supplied as a clear, colorless, preservative-free, isotonic sterile solution inphosphate-buffered saline, pH 7.3 that requires dilution prior to intravenous infusion. Each vial ofASPARLAS contains 3,750 units in 5 mL of solution. Each milliliter contains 750 units of calaspargasepegol-mknl; dibasic sodium phosphate, USP (5.58 mg); monobasic sodium phosphate, USP (1.20 mg); andsodium chloride, USP (8.50 mg) in water for injection, USP.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
L-asparaginase is an enzyme that catalyzes the conversion of the amino acid L-asparagine intoaspartic acid and ammonia.
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