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Pronunciation |
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(ay
za THYE oh
preen) |
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U.S. Brand
Names |
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Imuran® |
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Generic
Available |
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Yes |
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Synonyms |
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Azathioprine Sodium |
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Pharmacological Index |
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Immunosuppressant Agent |
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Use |
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Adjunct with other agents in prevention of rejection of solid organ
transplants; also used in severe active rheumatoid arthritis unresponsive to
other agents; other autoimmune diseases (ITP, SLE, MS, Crohn's Disease);
azathioprine is an imidazolyl derivative of
6-mercaptopurine |
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Pregnancy Risk
Factor |
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D |
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Contraindications |
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Hypersensitivity to azathioprine or any component; pregnancy and
lactation |
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Warnings/Precautions |
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Chronic immunosuppression increases the risk of neoplasia; has mutagenic
potential to both men and women and with possible hematologic toxicities; use
with caution in patients with liver disease, renal impairment; monitor
hematologic function closely |
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Adverse
Reactions |
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Dose reduction or temporary withdrawal allows reversal
Central nervous system: Fever, chills
Gastrointestinal: Nausea, vomiting, anorexia, diarrhea
Hematologic: Thrombocytopenia, leukopenia, anemia
Miscellaneous: Secondary infection
1% to 10%:
Dermatologic: Rash
Hematologic: Pancytopenia
Hepatic: Hepatotoxicity
<1%: Hypotension, alopecia, maculopapular rash, aphthous stomatitis,
arthralgias, which include myalgias, rigors, retinopathy, dyspnea, rare
hypersensitivity reactions |
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Overdosage/Toxicology |
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Symptoms of overdose include nausea, vomiting, diarrhea, hematologic toxicity
Following initiation of essential overdose management, symptomatic and
supportive treatment should be instituted. Dialysis has been reported to remove
significant amounts of the drug and its metabolites, and should be considered as
a treatment option in those patients who deteriorate despite established forms
of therapy. |
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Drug
Interactions |
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Increased toxicity: Allopurinol (decreases azathioprine dose to
1/3
to 1/4
of normal dose) |
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Stability |
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Stability of parenteral admixture at room temperature
(25°C ): 24 hours
Stability of parenteral admixture at refrigeration temperature
(4°C): 16 days
Stable in neutral or acid solutions, but is hydrolyzed to mercaptopurine in
alkaline solutions |
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Mechanism of
Action |
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Antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and
proteins; may also interfere with cellular metabolism and inhibit
mitosis |
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Pharmacodynamics/Kinetics |
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Distribution: Crosses the placenta
Protein binding: ~30%
Metabolism: Extensively by hepatic xanthine oxidase to 6-mercaptopurine
(active)
Half-life: Parent drug: 12 minutes; 6-mercaptopurine: 0.7-3 hours; End-stage
renal disease: Slightly prolonged
Elimination: Small amounts eliminated as unchanged drug; metabolites
eliminated eventually in urine |
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Usual Dosage |
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I.V. dose is equivalent to oral dose (dosing should be based on ideal
body weight):
Adults: Rheumatoid arthritis: Oral: 1 mg/kg/day for 6-8 weeks; increase by
0.5 mg/kg every 4 weeks until response or up to 2.5 mg/kg/day
Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer 75% of normal dose daily
Clcr <10 mL/minute: Administer 50% of normal dose daily
Hemodialysis: Slightly dialyzable (5% to 20%)
Administer dose posthemodialysis
CAPD effects: Unknown
CAVH effects: Unknown |
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Dietary
Considerations |
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May be administered with food |
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Monitoring
Parameters |
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CBC, platelet counts, total bilirubin, alkaline
phosphatase |
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Mental Health: Effects
on Mental Status |
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None reported |
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Mental Health:
Effects on Psychiatric
Treatment |
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May produce pancytopenia; use caution with clozapine and
carbamazepine |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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Take as prescribed (may take in divided doses or with food if GI upset
occurs).
Organ transplant: Azathioprine will usually be prescribed with other
antirejection medications.
You will be susceptible to infection (avoid vaccinations unless approved by
prescriber) and avoid crowds or infected persons or persons with contagious
diseases. You may experience nausea, vomiting, loss of appetite (small frequent
meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report
abdominal pain and unresolved gastrointestinal upset (eg, persistent vomiting or
diarrhea); unusual fever or chills, bleeding or bruising, sore throat, unhealed
sores, or signs of infection; yellowing of skin or eyes; or change in color of
urine or stool. Pregnancy/breast-feeding precautions: Do not get
pregnant while taking this medication; use appropriate barrier contraceptive
measures. Breast-feeding is not recommended. |
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Nursing
Implications |
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Can be administered IVP over 5 minutes at a concentration not to exceed 10
mg/mL; or azathioprine can be further diluted with normal saline or
D5W and administered by intermittent infusion over 15-60
minutes |
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Dosage Forms |
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Injection, as sodium: 100 mg (20 mL)
Tablet (scored): 50 mg |
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Extemporaneous
Preparations |
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A 50 mg/mL suspension compounded from twenty 50 mg tablets, distilled water,
Cologel® 5 mL, and then adding 2:1 simple syrup/cherry
syrup mixture to a total volume of 20 mL, was stable for 8 weeks when stored in
the refrigerator |
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References |
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American College of Rheumatology Ad Hoc Committee on Clinical Guidelines,
"Guidelines for Monitoring Drug Therapy in Rheumatoid Arthritis," Arthritis
Rheum, 1996, 39(5):723-31.
Baum D, Bernstein D, Starnes VA, et al,
"Pediatric Heart Transplantation at Stanford: Results of a 15-Year Experience,"
Pediatrics, 1991, 88(2):203-14.
Hutchins LF and Lipschitz DA, "Cancer, Clinical Pharmacology, and Aging,"
Clin Geriatr Med, 1987, 3(3):483-503.
Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure.
Position Statement.
"The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding,"
January 12, 1987.
Kaplan HG, "Use of Cancer Chemotherapy in the Elderly," Drug Treatment in
the Elderly, Vestal RE, ed, Boston, MA: ADIS Health Science Press, 1984,
338-49.
Leichter HE, Sheth KJ, Gerlach MJ, et al,
"Outcome of Renal Transplantation in Children Aged 1-5 and 6-18 Years," Child
Nephrol Urol, 1992, 12(1):1-5. |
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