ASPARLAS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ASPARLAS (ASPARLAS).
Asparaginase (ASPARLAS) hydrolyzes L-asparagine to L-aspartic acid and ammonia, depleting circulating asparagine. Leukemic cells with low asparagine synthetase activity rely on exogenous asparagine; depletion inhibits protein and nucleic acid synthesis, leading to cell death.
| Metabolism | ASPARLAS is a modified enzyme; it is not metabolized by hepatic cytochrome P450 enzymes. Clearance occurs via proteolysis and reticuloendothelial system uptake. |
| Excretion | Calaspargase pegol (ASPARLAS) is eliminated via the reticuloendothelial system; renal excretion is negligible (<2% unchanged), and biliary/fecal excretion has not been quantified. The pegylated asparaginase is cleared through proteolytic degradation. |
| Half-life | The terminal elimination half-life is approximately 25.7 days (range 17.8–33.6 days) in children and 22.0 days in adults, allowing for dosing every 2 weeks instead of 3 times per week as with native E. coli asparaginase. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin and immunoglobulins, though binding is non-specific and not saturable at therapeutic concentrations. |
| Volume of Distribution | The volume of distribution is approximately 3.5 L/m² (not routinely expressed in L/kg; in children, estimated Vd ~0.1–0.2 L/kg), indicating limited extravascular distribution, primarily confined to the intravascular space. |
| Bioavailability | Administered only intravenously; bioavailability is 100% by IV route. |
| Onset of Action | Intravenous administration: Asparagine depletion occurs within 24 hours post-dose, achieving nadir asparagine levels (<1 μM) by day 3–5. |
| Duration of Action | Asparagine depletion persists for approximately 2–4 weeks after a single IV dose (2,500 IU/m²), with nadir levels maintained for at least 14 days, supporting every-2-week dosing. |
Intravenous (IV) or intramuscular (IM) injection: 2,500 IU/m² every 14 days as a component of multi-agent chemotherapy. Administer IV over 1-2 hours in 100 mL of 0.9% sodium chloride.
| Dosage form | INJECTABLE |
| Renal impairment | No standard dose adjustment guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment; monitor liver function closely in Child-Pugh class A. |
| Pediatric use | Same as adult dosing: 2,500 IU/m² IV or IM every 14 days; based on body surface area calculated using the Mosteller formula. |
| Geriatric use | No specific dose adjustments; monitor renal and hepatic function more frequently due to age-related decline, and consider increased risk of neurotoxicity and thrombosis. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ASPARLAS (ASPARLAS).
| Breastfeeding | No human data; M/P ratio unknown. Excretion in animal milk reported. Risk of serious adverse reactions in breastfed infant; avoid breastfeeding during therapy and for 1 month after last dose. |
| Teratogenic Risk | First trimester: Limited data; animal studies show potential embryotoxicity and skeletal abnormalities. Second trimester: Potential risk of fetal hepatotoxicity and coagulopathy. Third trimester: Increased risk of maternal thrombosis and fetal distress due to placental effects. |
| Fetal Monitoring |
■ FDA Black Box Warning
Risk of serious hypersensitivity reactions, including anaphylaxis, and pancreatitis. Observe patients for 1 hour after administration and have appropriate resuscitation equipment available.
| Serious Effects |
["History of serious hypersensitivity reactions (e.g., anaphylaxis) to asparaginase products","History of pancreatitis related to prior asparaginase therapy","History of serious thrombosis (e.g., cerebral sinus thrombosis) related to prior asparaginase therapy","History of serious hemorrhagic events related to prior asparaginase therapy"]
| Precautions | ["Serious hypersensitivity reactions (including anaphylaxis); contraindicated in patients with history of serious hypersensitivity to asparaginase products.","Pancreatitis: monitor for abdominal pain; discontinue if pancreatitis occurs.","Thrombosis and hemorrhage: monitor coagulation parameters; use caution in patients with coagulopathy.","Hepatotoxicity: monitor liver function tests; dose adjustment may be required.","Glucose intolerance: monitor blood glucose; may require insulin therapy."] |
| Food/Dietary |
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| Monitor complete blood count, liver function tests (ALT, AST, bilirubin), renal function (creatinine), coagulation parameters (PT, aPTT, fibrinogen), and serum ammonia levels. Fetal ultrasound for growth and anatomy if exposure in first trimester. Maternal monitoring for thrombosis and pancreatitis. |
| Fertility Effects | Based on animal studies, may impair female fertility; effects on male fertility unknown. Long-term reproductive function data not available. |
| No specific food interactions have been established. However, as a precaution, maintain adequate hydration to reduce risk of hyperuricemia from rapid cell lysis. Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction (though not extensively studied). |
| Clinical Pearls | ASPARLAS (calaspargase pegol-mknl) is a long-acting PEGylated asparaginase for ALL. Monitor for hypersensitivity reactions, especially in patients with previous asparaginase allergy. Prophylactic antihistamines may be considered. Contraindicated in severe hepatic impairment, pancreatitis, and thrombosis. Check amylase, lipase, and liver function before each dose. Administer IV over 10–30 minutes; do not administer IM or SC. Dose adjustment for toxicity may be necessary. |
| Patient Advice | This medication can cause serious allergic reactions; seek emergency care if you experience hives, difficulty breathing, or swelling. · Report any new abdominal pain, nausea, vomiting, or back pain (signs of pancreatitis). · Avoid alcohol as it may increase risk of liver problems. · Watch for signs of bleeding or bruising (low platelet count) or signs of infection (fever, sore throat). · Do not receive live vaccines during treatment. |