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Look Up > Drugs > Azathioprine
Azathioprine
Pronunciation
U.S. Brand Names
Generic Available
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Monitoring Parameters
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
Extemporaneous Preparations
References

Pronunciation
(ay za THYE oh preen)

U.S. Brand Names
Imuran®

Generic Available

Yes


Synonyms
Azathioprine Sodium

Pharmacological Index

Immunosuppressant Agent


Use

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


Pregnancy Risk Factor

D


Contraindications

Hypersensitivity to azathioprine or any component; pregnancy and lactation


Warnings/Precautions

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


Adverse Reactions

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


Overdosage/Toxicology

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.


Drug Interactions

Increased toxicity: Allopurinol (decreases azathioprine dose to 1/3 to 1/4 of normal dose)


Stability

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


Mechanism of Action

Antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins; may also interfere with cellular metabolism and inhibit mitosis


Pharmacodynamics/Kinetics

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


Usual Dosage

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


Dietary Considerations

May be administered with food


Monitoring Parameters

CBC, platelet counts, total bilirubin, alkaline phosphatase


Mental Health: Effects on Mental Status

None reported


Mental Health: Effects on Psychiatric Treatment

May produce pancytopenia; use caution with clozapine and carbamazepine


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

No effects or complications reported


Patient Information

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.


Nursing Implications

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


Dosage Forms

Injection, as sodium: 100 mg (20 mL)

Tablet (scored): 50 mg


Extemporaneous Preparations

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


References

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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