Azathioprine

Azathioprine tablets, USP are indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. Renal Homotransplantation Azathioprine tablets, USP are indicated as an adjunct for the prevention of rejection in renal homotransplantation. Experience with over 16,000 transplants shows a 5-year patient survival of 35% to 55%, but this is dependent on donor, match for HLA antigens, anti-donor or anti-B-cell alloantigen antibody, and other variables. The effect of azathioprine tablets on these variables has not been tested in controlled trials. …

• Renal Homotransplantation The dose of azathioprine tablets required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management
• The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant
• Azathioprine tablets are usually given as a single daily dose on the day of, and in a minority of cases 1 to 3 days before, transplantation
• Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible
• The dose of azathioprine tablets should not be increased to toxic levels because of threatened rejection
• Discontinuation may be necessary for severe hematologic or other toxicity, even if rejection of the homograft may be a consequence of drug withdrawal
• Rheumatoid Arthritis Azathioprine tablets are usually given on a daily basis
• The initial dose should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice-daily schedule
• The dose may be increased, beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals, if there are no serious toxicities and if initial response is unsatisfactory
• Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day
• Therapeutic response occurs after several weeks of treatment, usually 6 to 8; an adequate trial should be a minimum of 12 weeks
• Patients not improved after 12 weeks can be considered refractory. …

• Safety and efficacy of azathioprine
• In pediatric patients have not been established

• Patients being started on azathioprine tablets should be informed of the necessity of periodic blood counts while they are receiving the drug and should be encouraged to report any unusual bleeding or bruising to their physician
• They should be informed of the danger of infection while receiving azathioprine tablets and asked to report signs and symptoms of infection to their physician
• Careful dosage instructions should be given to the patient, especially when azathioprine tablets are being administered in the presence of impaired renal function or concomitantly with allopurinol (see Drug Interactions subsection and DOSAGE AND ADMINISTRATION ). …

• Azathioprine tablets should not be given to patients who have shown hypersensitivity to the drug
• Azathioprine tablets should not be used for treating rheumatoid arthritis in pregnant women
• Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others) may have a prohibitive risk of malignancy if treated with azathioprine tablets

Use with xanthine oxidase (XO) inhibitors: One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of azathioprine, to approximately 1/ 3 to 1/ 4 the usual dose. Concomitant use of azathioprine with febuxostat is not recommended. Inhibition of XO may cause increased plasma concentrations of azathioprine or its metabolite, 6-MP, leading to toxicity. …

Malignancy Patients receiving immunosuppressants, including azathioprine, are at increased risk of developing lymphoma and other malignancies, particularly of the skin. Physicians should inform patients of the risk of malignancy with azathioprine. As usual 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. Post-transplant Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. …

The principal and potentially serious toxic effects of azathioprine tablets are hematologic and gastrointestinal. The risks of secondary infection and malignancy are also significant (see WARNINGS ). The frequency and severity of adverse reactions depend on the dose and duration of azathioprine tablets as well as on the patient’s underlying disease or concomitant therapies. The incidence of hematologic toxicities and neoplasia encountered in groups of renal homograft recipients is significantly higher than that in studies employing azathioprine tablets for rheumatoid arthritis. …

Pregnancy Azathioprine tablets can cause fetal harm when administered to a pregnant woman. Azathioprine tablets should not be given during pregnancy without careful weighing of risk versus benefit. Whenever possible, use of azathioprine tablets in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women. …

The oral LD 50 s for single doses of azathioprine tablets in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death. About 30% of azathioprine is bound to serum proteins, but approximately 45% is removed during an 8-hour hemodialysis. 14 A single case has been reported of a renal transplant patient who ingested a single dose of 7500 mg azathioprine. The immediate toxic reactions were nausea, vomiting, and diarrhea, followed by mild leukopenia and mild abnormalities in liver function. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.