AZATHIOPRINE, AZATHIOPRINE SODIUM
Chemistry - Related structurally to adenine, guanine and hypoxanthine, azathioprine is a purineantagonist antimetabolite that is used primarily for its immunosuppressive properties. Azathioprineoccurs as an odorless, pale yellow powder that is insoluble in water and slightly soluble in alcohol.
Azathioprine sodium powder for injection occurs as a bright yellow, amorphous mass. Afterreconstituting with sterile water for injection to a concentration of 10 mg/ml it has an approximatepH of 9.6.
The sodium powder for injection should be stored at room temperature and protected from light. Itis reportedly stable at neutral or acidic pH, but will hydrolyze to mercaptopurine in alkalinesolutions. This conversion is enhanced upon warming or in the presence of sulfhydryl-containingcompounds (e.g., cysteine). After reconstituting, the injection should be used within 24 hours as nopreservative is present.
Azathioprine sodium is reportedly compatible with the following intravenous solutions: dextrose5% in water, and sodium chloride 0.45% or 0.9%. Compatibility is dependent upon factors such aspH, concentration, temperature and diluents used. It is suggested to consult specialized referencesfor more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Clinical response to azathioprine may require up to 6 weeks.
Uses, Indications - In veterinary medicine, azathioprine is used primarily as a second or third line immunosuppressive agent in the treatment of immune-mediated diseases in dogs. See Doses below for more information.
Azathioprine is mutagentic and teratogenic (in lab animals).
Because azathioprine depresses the immune system, animals may be susceptible to infections orneoplastic illnesses (long-term use).
In recovering dogs with immune-mediated hemolytic anemia, taper the withdrawal of the drugslowly over several months and monitor for early signs of relapse. Rapid withdrawal can lead to arebound hyperimmune response.
The neuromuscular blocking activity of non-depolarizing muscle relaxants (e.g., pancuronium, tubocurarine) may be inhibited or reversed by azathioprine.
Azathioprine sodium powder for injection occurs as a bright yellow, amorphous mass. Afterreconstituting with sterile water for injection to a concentration of 10 mg/ml it has an approximatepH of 9.6.
Storage, Stability, Compatibility
Azathioprine tablets should be stored at room temperature inwell-closed containers and protected from light.The sodium powder for injection should be stored at room temperature and protected from light. Itis reportedly stable at neutral or acidic pH, but will hydrolyze to mercaptopurine in alkalinesolutions. This conversion is enhanced upon warming or in the presence of sulfhydryl-containingcompounds (e.g., cysteine). After reconstituting, the injection should be used within 24 hours as nopreservative is present.
Azathioprine sodium is reportedly compatible with the following intravenous solutions: dextrose5% in water, and sodium chloride 0.45% or 0.9%. Compatibility is dependent upon factors such aspH, concentration, temperature and diluents used. It is suggested to consult specialized referencesfor more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology - AZATHIOPRINE, AZATHIOPRINE SODIUM
While the exact mechanism how azathioprine exerts its immunosuppressive action has not been determined, it is probably dependent on several factors. Azathioprine antagonizes purine metabolism thereby inhibiting RNA, DNA synthesis and mitosis. It also may cause chromosome breaks secondary to incorporation into nucleic acids and cellular metabolism may become disrupted by the drug's ability to inhibit coenzyme formation. Azathioprine has greater activity on delayed hypersensitivity and cellular immunity than on humoral antibody responses.Clinical response to azathioprine may require up to 6 weeks.
Uses, Indications - In veterinary medicine, azathioprine is used primarily as a second or third line immunosuppressive agent in the treatment of immune-mediated diseases in dogs. See Doses below for more information.
Pharmacokinetics - AZATHIOPRINE, AZATHIOPRINE SODIUM
Azathioprine is absorbed from the GI tract and is rapidly metabolized tomercaptopurine which is then further metabolized to several other compounds. These metabolitesare excreted by the kidneys. Only minimal amounts of either azathioprine or mercaptopurine areexcreted unchanged.Contraindications, Precautions, Reproductive Safety
Azathioprine is contraindicated in patients hypersensitive to it. The drug should be used cautiously in patients with hepatic dysfunction.Azathioprine is mutagentic and teratogenic (in lab animals).
Adverse Effects, Warnings
The principal adverse effect associated with azathioprine is bonemarrow suppression. Cats are more prone to develop these effects and the drug is generally notrecommended to be used in that species. Leukopenia is the prevalent consequence, but anemias andthrombocytopenia may also be seen. Acute pancreatitis and hepatotoxicity have also been associatedwith azathioprine therapy in dogs.Because azathioprine depresses the immune system, animals may be susceptible to infections orneoplastic illnesses (long-term use).
In recovering dogs with immune-mediated hemolytic anemia, taper the withdrawal of the drugslowly over several months and monitor for early signs of relapse. Rapid withdrawal can lead to arebound hyperimmune response.
Overdosage, Acute Toxicity
No specific information was located regarding acute overdose ofazathioprine. It is suggested to use standard protocols to empty the GI tract if ingestion was recentand to treat supportively.Drug Interactions
The hepatic metabolism of azathioprine may be decreased by concomitantadministration of allopurinol. In humans, it is recommended to reduce the azathioprine dose to1/4-1/3 usual if both drugs are to used together.The neuromuscular blocking activity of non-depolarizing muscle relaxants (e.g., pancuronium, tubocurarine) may be inhibited or reversed by azathioprine.