azathioprine

Absorption: Readily absorbed after oral administration. IV administration results in complete bioavailability.

Distribution: Unknown

Metabolism/Excretion: Metabolized to 6-mercaptopurine, which is further metabolized (one route is by thiopurine methyltransferase [TPMT] to form an inactive metabolite; nucleotide diphosphatase [NUDT15] is also involved in inactivation process). Minimal renal excretion of unchanged drug.

Half-Life: 3 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO (anti-inflammatory)	6–8 wk	12 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of mycophenolate;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Infection;
Malignancies;
↓bone marrow reserve;
Previous or concurrent radiation therapy;
Severe renal impairment/oliguria (↑ sensitivity);
TPMT or NUDT15 enzyme deficiency (alternative therapy or substantial dose ↓ are required to avoid hematologic adverse events);
Rep: Women of reproductive potential;
Pedi: risk of hepatosplenic T-cell lymphoma (HSTCL) in children with inflammatory bowel disease.

Adv. Reactions/Side Effects ⬆ ⬇

CV: Raynaud's phenomenon

Derm: alopecia, rash

EENT: retinopathy

GI: anorexia, hepatotoxicity, nausea, vomiting, diarrhea, mucositis, pancreatitis

Hemat: anemia, leukopenia, pancytopenia, thrombocytopenia

MS: arthralgia

Neuro: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Resp: pulmonary edema

Misc: chills, fever, MALIGNANCY (INCLUDING POST-TRANSPLANT LYMPHOMA, HSTCL, AND SKIN CANCER), SERUM SICKNESS

Interactions ⬆ ⬇

Drug-drug:

Febuxostat may ↑ levels and risk of toxicity; concurrent use not recommended.
Additive myelosuppression with antineoplastics, cyclosporine, and myelosuppressive agents.
Allopurinol may ↑ levels and risk of toxicity. ↓ azathioprine dose to 25–33% of the usual dose.
May ↓ antibody response to live-virus vaccines and ↑ the risk of adverse reactions.

Drug-Natural Products:

Concomitant use with echinacea and melatonin may interfere with immunosuppression.

Route/Dosage ⬆ ⬇

Renal Allograft Rejection Prevention

PO IV (Adults and Children ): 3–5 mg/kg/day initially; maintenance dose 1–3 mg/kg/day.

Rheumatoid Arthritis

PO IV (Adults and Children ): 1 mg/kg/day for 6–8 wk; ↑ by 0.5 mg/kg/day every 4 wk until response or up to 2.5 mg/kg/day; then ↓ by 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; may ↑ 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
Powder for injection: 100 mg/vial

Assessment ⬆ ⬇

Assess for infection (vital signs, sputum, urine, stool, WBC) during therapy.
- Monitor intake and output and daily weight. Decreased urine output may lead to toxicity with this medication.
- Monitor for signs of malignancy (splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss).
- Monitor for signs of PML (confusion, depression, trouble with memory, behavioral changes, changes in strength on one side, difficulty speaking, change in balance or vision).
Rheumatoid Arthritis: Assess range of motion; degree of swelling, pain, and strength in affected joints; and ability to perform activities of daily living before and periodically during therapy.

Lab Test Considerations:

Monitor renal, hepatic, and hematologic functions before beginning therapy, weekly during the 1st mo, bimonthly for the next 2–3 mo, and monthly thereafter.
- Leukocyte count of <3000/mm³ or platelet count of <100,000/mm³ may necessitate a reduction in dose or temporary discontinuation.
- ↓in hemoglobin may indicate bone marrow suppression.
- Hepatotoxicity may be manifested by ↑ alkaline phosphatase, bilirubin, AST, ALT, and amylase concentrations. Usually occurs within 6 mo of transplant, rarely with rheumatoid arthritis, and is reversible on discontinuation of azathioprine.
- May ↓ serum and urine uric acid and plasma albumin.

Implementation ⬆ ⬇

Do not confuse azathioprine with azacitidine.
- Protect transplant patients from staff members and visitors who may carry infection. Maintain protective isolation as indicated.
PO: May be administered with or after meals or in divided doses to minimize nausea.
IV: Reconstitution: Add 10 mL of sterile water for injection, and swirl until a clear solution results. Solution is equivalent to 100 mg of azathioprine; it is for IV use only, has a pH of approximately 9.6, and should be used within 24 hr.Diluent: Further dilute with 0.9% NaCl or D5W; final volume depends on time for the infusion, usually 30 to 60 min, but as short as 5 min and as long as 8 hr for the daily dose. Inspect solution for particulate matter and discoloration prior to administration.
Rate: Infuse over 30–60 min; 5 min to 8 hr have been used.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take azathioprine as directed. If a dose is missed on a once-daily regimen, omit dose; if a dose is missed on several-times-a-day dosing, take as soon as possible or double next dose. Consult health care professional if more than 1 dose is missed or if vomiting occurs shortly after dose is taken. Do not discontinue without consulting health care professional.
- Advise patient to report unusual tiredness or weakness; cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination; severe diarrhea; black, tarry stools; blood in urine; or transplant rejection to health care professional immediately.
- Reinforce the need for lifelong therapy to prevent transplant rejection.
- Inform patient of increased risk of malignancy. For patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications or receiving any vaccinations while taking this medication.
- Advise patient to avoid contact with persons with contagious diseases and persons who have recently taken oral poliovirus vaccine or other live viruses.
- May cause fetal harm. Advise patient to use contraception during and for at least 4 mo after therapy is completed and to avoid breastfeeding during therapy. May also cause intrahepatic cholestasis of pregnancy.
- Emphasize the importance of follow-up exams and lab tests.
Rheumatoid Arthritis: Concurrent therapy with salicylates, NSAIDs, or corticosteroids may be necessary. Patient should continue physical therapy and adequate rest. Explain that joint damage will not be reversed; goal is to slow or stop disease process.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇