Asparaginase
Asparaginase is a unique, enzyme-based **antineoplastic agent** primarily used in veterinary oncology to treat **lymphoid malignancies** (such as lymphoma) and **leukemias** (especially Acute Lymphoblastic Leukemia or ALL) in dogs and cats. Unlike traditional chemotherapy drugs that directly damage DNA, asparaginase works by starving cancer cells of a vital nutrient. Because it generally spares the bone marrow (minimal myelosuppression) and gastrointestinal mucosa, it is an excellent choice for induction protocols or as a "rescue" therapy when a patient's bone marrow is already compromised. **Clinical Pearl:** Because asparaginase is a large, foreign protein (derived from *E. coli*), hypersensitivity/anaphylaxis is a major clinical concern. Furthermore, its efficacy often drops over time due to the patient's immune system producing neutralizing antibodies against the enzyme.
Mecanismo: Normal cells can synthesize their own asparagine using the enzyme **asparagine synthetase**. However, many lymphoid malignant cells lack this enzyme and rely entirely on exogenous asparagine from the bloodstream for protein and DNA synthesis. Asparaginase is an enzyme that circulates in the intravascular space and catalyzes the breakdown of circulating asparagine: **L-asparagine** + H2O → (via **L-asparaginase**) → **Aspartic acid** + **Ammonia** By rapidly depleting circulating asparagine, the drug halts protein synthesis in the tumor cells, leading to apoptosis. The antineoplastic activity is greatest during the post-mitotic (**G1**) phase of the cell cycle.
Dosificación por especie
- Lymphoid malignancies / Leukemia · 400 Units/kg or 10,000 Units/m2 IM or SC, with a maximum dose of 10,000 Units per patient · IM/SC · Protocol dependent · Protocol dependent · Many oncologists recommend administering diphenhydramine at 2 mg/kg SC 30 minutes prior to administration.
- Treatment of lymphoid malignancies · 10,000 IU/m2 or 400 IU/kg · IM/SC · q7d or less frequently · As per chemotherapy protocol · See specialist texts for chemotherapy protocols and conversion of body weight to body surface area.
- Lymphoid malignancies / Leukemia · 400 Units/kg or 10,000 Units/m2 IM or SC, with a maximum dose of 10,000 Units per patient · IM/SC · Protocol dependent · Protocol dependent · Many oncologists recommend administering diphenhydramine at 1 mg/kg SC 30 minutes prior to administration.
- Treatment of lymphoid malignancies · 10,000 IU/m2 or 400 IU/kg · IM/SC · q7d or less frequently · As per chemotherapy protocol · See specialist texts for chemotherapy protocols and conversion of body weight to body surface area.
Las dosis son una referencia clínica para veterinarios colegiados. Confirme siempre con la ficha técnica vigente y el paciente individual.
Vías de administración
Contraindicaciones
- Patients with a history of anaphylaxis to asparaginase
- Patients with pancreatitis or a history of pancreatitis
Efectos adversos
- Hypersensitivity reactions (vomiting, diarrhea, urticaria, pruritus, dyspnea, hypotension, collapse)
- Hemorrhagic pancreatitis
- Hepatotoxicity
- Coagulation defects
- Hyperglycemia (secondary to altered insulin synthesis)
- Leukopenia (rare)
Interacciones farmacológicas
- Methotrexate · Asparaginase may reduce methotrexate effectiveness against tumor cells until serum asparagine levels return to normal.
- Prednisone · Concurrent use may increase the risk for hyperglycemia.
- Vincristine · Increased toxicity (neuropathy and erythropoiesis disruption) and myelosuppression may occur. Some oncologists recommend separating the dosing by a few days to a week. · major
Monitorización
- Hepatic function
- Renal function (BUN may be increased by drug action)
- Pancreatic function (blood glucose, amylase)
- Hematopoietic function
- Patient observation for hypersensitivity during and immediately after administration
- Serum ammonia (may be increased)
Sobredosis
In dogs, the maximally tolerated dose is 10,000 IU/kg and the lethal dose is 50,000 IU/kg. Overdosage is expected to cause severe toxicity secondary to protein synthesis alteration (pancreatitis, hepatotoxicity, coagulopathy). Treatment is supportive.
La referencia de fármacos de VetSheet está destinada a veterinarios colegiados como apoyo a la decisión clínica, no sustituye el juicio profesional ni la ficha técnica vigente del fabricante.