Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

ASPARAGINASE

Chemistry - Asparaginase is an enzyme derived from E. coli and occurs as a white or almost white, slightly hygroscopic powder that is soluble in water. The commercially available product is alyophilized powder that also contains mannitol which after reconstituting has a pH of about 7.4.
Activity of asparaginase is expressed in terms of International Units ((I.U.). Asparaginase may alsobe known by the following monikers: L-asparaginase, L-asparagine amidohydrolase, Coloaspase,
A-ase, or ASN-ase.

Storage, Stability, Compatibility

Asparaginase powder for injection should be stored at temperatures less than 8°C, but it is stable for at least 48 hours at room temperature. After reconstituting, the manufacturer states that the drug is stable when refrigerated for up to 8 hours, but othersources state that it is stable for up to 14 days.
Solutions should be used only if clear; turbid solutions should be discarded. Upon standing, gelatinous fibers may be noted in the solution occasionally. These may be removed without loss ofpotency with a 5 micron filter. Some loss of potency may occur if a 0.2 micron filter is used.
The solution may be shaken while reconstituting, but vigorous shaking should be avoided as thesolution may become foamy and difficult to withdraw from the vial, and some loss of potency canalso occur. Recommended intravenous diluents for asparaginase include D5W and sodium chloride0.9%.

Pharmacology - ASPARAGINASE

Some malignant cells are unable to synthesize asparagine and are dependent onexogenous asparagine for DNA and protein synthesis. Asparaginase catalyzes asparagine intoammonia and aspartic acid. The antineoplastic activity of asparaginase is greatest during thepostmitotic (G1) cel phase. While normal cells are able to synthesize asparagine intracellularly, some normal cells having a high rate of protein synthesis require some exogenous asparagine andmay be adversely affected by asparaginase.
Resistance to asparaginase can develop rapidly, but apparently there is no cross-resistance betweenasparaginase and other antineoplastic agents.
Asparaginase possesses antiviral activity, but its toxicity prevents it from being clinically useful inthis regard.
Uses, Indications - Asparaginase has been useful in combination with other agents in the treatmentof lymphosarcoma in dogs. The drug is most useful in inducing remission of disease, but isoccasionally used in some maintenance protocols.

Pharmacokinetics - ASPARAGINASE

Asparaginase is not absorbed from the GI tract and must be given either IV or IM. After IM injection, serum levels of asparaginase are approximately 1/2 of those after IVinjection. Because of its high molecular weight, asparaginase does not diffuse readily out of thecapillaries and about 80% of the drug remains within the intravascular space.
In humans after IV dosing, serum levels of asparagine fall almost immediately to zero and remainthat way as long as therapy continues. Once therapy is halted, serum levels of asparagine do notrecover for at least 23 days.
The metabolic fate of asparaginase is not known. In humans, the plasma half-life is highly variableand ranges from 8-30 hours.

Contraindications, Precautions, Reproductive Safety

Asparaginase is contraindicated in patients who have exhibited anaphylaxis to it, or in patients with pancreatitis or a history of pancreatitis. Asparaginase should be used with caution in patients with preexisting hepatic, renal, hematologic, gastrointestinal, or CNS dysfunction.
No special precautions are required for handling asparaginase, but any inadvertent skin contactshould be washed off as the drug can be a contact irritant.

Adverse Effects, Warnings

Asparaginase adverse reactions are classified in two main categories, hypersensitivity reactions and its effects on protein synthesis. Hypersensitivity reactions can occurwith symptoms of vomiting, diarrhea, urticaria, pruritis, dyspnea, restlessness, hypotension andcollapse. The likelihood of hypersensitivity reactions occurring increases with subsequent dosesand intravenous administration. Some clinicians recommend giving a test dose before the full doseto test for local hypersensitivity and/or administering antihistamines (e.g., diphenhydramine) priorto dosing. If a hypersensitivity reaction occurs, diphenhydramine (0.2 - 0.5 mg/kg slow IV), dexamethasone sodium phosphate (1 - 2 mg/kg IV), intravenous fluids and, if severe, epinephrine(0.1 - 0.3 ml of a 1:1000 solution IV) have been suggested (O'Keefe and Harris 1990).
The other broad category of toxicity is associated with asparaginase's effects on protein synthesis.
Hemorrhagic pancreatitis or other gastrointestinal disturbances, hepatotoxicity and coagulationdefects may be noted. Large doses may be associated with hyperglycemia secondary to alteredinsulin synthesis. Bone marrow depression is an uncommon consequence of asparaginase therapy, but leukopenia has been reported.
Overdosage, Acute Toxicity - Little information was located regarding overdosages with thisagent. It would be expected that toxicity secondary to the protein synthesis altering effects of thedrug would be encountered. In dogs it has been reported that the maximally tolerated dose of asparaginase is 10, 000 IU/kg and the lethal dose is 50, 000 IU/kg.
It is recommended to treat supportively if an overdose occurs.

Drug Interactions

Asparaginase may reduce methotrexate effectiveness against tumor cellsuntil serum asparagine levels return to normal.
In humans, increased toxicity may occur when asparaginase (IV) is given concurrently with orbefore prednisone and vincristine.
Drug/Laboratory Interactions - Serum ammonia and urea nitrogen levels may be increasedby the action of the drug.
Asparaginase may cause rapid (within 2 days) and profound decreases in circulating thyroxine-binding globulin, which may alter interpretation of thyroid function studies. Values may return tonormal after approximately 4 weeks.
Click here add new comment/review

veterinary-help.com

© 2011-2024 Veterinary Clinics, Diagnoses, Terms and Drug Handbook Online

×
Wait 20 seconds...!!!