Azasan (Azathioprine) - Indications and Dosage

INDICATIONS AND USAGE

AZASAN® is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin, or other nonsteroidal anti-inflammatory drugs, or to agents in the class of which gold is an example.

Renal Homotransplantation:    AZASAN® is 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 and anti B-cell alloantigen antibody, and other variables. The effect of azathioprine on these variables has not been tested in controlled trials.

Rheumatoid Arthritis:    AZASAN® is indicated only in adult patients meeting criteria for classic or definite rheumatoid arthritis as specified by the American Rheumatism Association. AZASAN® should be restricted to patients with severe, active and erosive disease not responsive to conventional management including rest, aspirin, or other nonsteroidal drugs or to agents in the class of which gold is an example. Rest, physiotherapy, and salicylates should be continued while AZASAN® is given, but it may be possible to reduce the dose of corticosteroids in patients on AZASAN®. The combined use of AZASAN® with gold, antimalarials, or penicillamine has not been studied for either added benefit or unexpected adverse effects. The use of AZASAN® with these agents cannot be recommended.

DOSAGE AND ADMINISTRATION

Renal Homotransplantation:    The dose of AZASAN® 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. AZASAN® is usually given as a single daily dose on the day of, and in a minority of cases 1 to 3 days before, transplantation. AZASAN® is often initiated with the intravenous administration of the sodium salt, with subsequent use of tablets (at the same dose level) after the postoperative period. Intravenous administration of the sodium salt is indicated only in patients unable to tolerate oral medications. Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible. The dose of AZASAN® 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:    AZASAN® is usually given on a daily basis. The initial dose should be approximately 1 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/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. AZASAN® may be continued long-term in patients with clinical response, but patients should be monitored carefully, and gradual dosage reduction should be attempted to reduce risk of toxicities.

Maintenance therapy should be at the lowest effective dose, and the dose given can be lowered decrementally with changes of 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant. The optimum duration of maintenance AZASAN® has not been determined. AZASAN® can be discontinued abruptly, but delayed effects are possible.

Use in Renal Dysfunction:    Relatively oliguric patients, especially those with tubular necrosis in the immediate post-cadaveric transplant period, may have delayed clearance of AZASAN® or its metabolites, may be particularly sensitive to this drug, and are usually given lower doses.

Procedures for proper handling and disposal of this immunosuppressive antimetabolite drug should be considered. Several guidelines on this subject have been published. ^1-7 There is no general agreement that all of the procedures recommended in the guideline are necessary or appropriate.

HOW SUPPLIED

AZASAN® Tablets, USP are available in:

25 mg, oval-shaped, yellow, scored tablets,

100 count bottles (NDC 65649-251-41)

15 count samples (NDC 65649-251-51)

75 mg, triangle-shaped, yellow, scored tablets,

100 count bottles (NDC 65649-231-41)

15 count samples (NDC 65649-231-51)

100 mg, diamond-shaped, yellow, scored tablets,

100 count bottles (NDC 65649-241-41)

15 count samples (NDC 65649-241-51)

Rx only.

Store at 20° to 25°C (68° to 77° F) [See USP Controlled Room Temperature]

Store in a dry place and protect from light.

Dispense in a tight, light-resistant container as defined in the USP.