azaTHIOprine, Azasan, Imuran

 Indications

Prevention of renal transplant rejection (with corticosteroids,

local radiation, or other cytotoxic agents).

Treatment of severe, active, erosive rheumatoid arthritis

unresponsive to more conventional therapy. Unlabeled

Use: Management of Crohn’s disease or ulcerative

colitis.

Action

Antagonizes purine metabolism with subsequent inhibition

of DNA and RNA synthesis. Therapeutic Effects:

Suppression of cell-mediated immunity and altered

antibody formation.

Pharmacokinetics

Absorption: Readily absorbed after oral administration.

Distribution: Crosses the placenta. Enters breast

milk in low concentrations.

Metabolism and Excretion: Metabolized to mercaptopurine,

which is further metabolized (one route

is by thiopurine methyltransferase [TPMT] to form an

inactive metabolite). Minimal renal excretion of unchanged

drug. 

Half-life: 3 hr. A

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

PO (anti-inflammatory)

6–8 wk 12 wk unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use of mycophenolate; OB: Has been shown to cause fetal

harm; Lactation: Appears in breast milk .

Use Cautiously in: Infection; Malignancies;pbone

marrow reserve; Previous or concurrent radiation therapy;

Other chronic debilitating illnesses; Severe renal

impairment/oliguria (qsensitivity); Patients with

TPMT enzyme deficiency (substantial dosepare required

to avoid hematologic adverse events); Rep:

Women of reproductive potential; Pedi:qrisk of hepatosplenic

T-cell lymphoma [HSTCL] in patients with inflammatory

bowel disease.

Adverse Reactions/Side Effects

CNS: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY.

EENT: retinopathy. Resp: pulmonary edema. GI:

anorexia, hepatotoxicity, nausea, vomiting, diarrhea,

mucositis, pancreatitis. Derm: alopecia, rash. Hemat:

anemia, leukopenia, pancytopenia, thrombocytopenia.

MS: arthralgia. Misc: MALIGNANCY (including

post-transplant lymphoma, HSTCL, and skin cancer),

SERUM SICKNESS, chills, fever, Raynaud’s phenomenon,

retinopathy.

Interactions

Drug-Drug: Additive myelosuppression with antineoplastics,

cyclosporine, and myelosuppressive

agents. Allopurinol inhibits the metabolism of azathioprine,

increasing toxicity. Dose of azathioprine

should bepto 25–33% of the usual dose when used

with allopurinol. Maypantibody response to live-virus

vaccines andqthe risk of adverse reactions.

Drug-Natural Products: Concommitant use with

echinacea and melatonin may interfere with immunosuppression.

Route/Dosage

Renal Allograft Rejection Prevention

PO (Adults and Children): 3–5 mg/kg/day initially;

maintenance dose 1–3 mg/kg/day.

Rheumatoid Arthritis

PO (Adults and Children): 1 mg/kg/day for 6–8 wk,

qby 0.5 mg/kg/day every 4 wk until response or up to

2.5 mg/kg/day, thenpby 0.5 mg/kg/day every 4–8 wk

to minimal effective dose.

Inflammatory Bowel Disease (Crohn’s

Disease or Ulcerative Colitis) (unlabeled

use)

PO (Adults and Children): 50 mg once daily; mayq

by 25 mg/day every 1–2 wk as tolerated to target dose

of 2–3 mg/kg/day.

Availability (generic available)

Tablets: 50 mg, 75 mg, 100 mg.