DESCRIPTION:
Yellow, round, beveled-edge tablet, scored on one side, marked with “AZ”on the other side.
INDICATIONS:
Immunosuppressant after renal homotransplantations auto-immune disorder
Treatment of rheumatoid arthritis
DOSAGE & ADMINISTRATION
Renal transplantation: The usual oral dosage in children and adults undergoing renal transplantation is 3-5 mg/kg beginning on te day of transplantation. Dosage reduction to maintenance levels of 1-3 mg/kg daily is usually possible.
Rheumatoid Arthriti: For the treatment of severe, active rheumatoid arthritis, the usual initial oral adult dosage of azathioprine is 1mg/kg (approximately 50-100mg) daily. If the initial response is unsatisfactory and no serious adverse effects occur after 6-8 weeks of therapy, daily dosage may be increased by 0.5mg/kg; daily dosage may then be increased as necessary at 4 week intervals by 0.5 mg/kg up to a maximum of 2.5 mg/kg. A therapeutic response usually occurs after 6-8 weeks of therapy; an adequate trial should be a minimum of 12 weeks.
Or as prescribed by the physician.
CONTRAINDICATIONS
Azathioprine should not be given to patients who have shown hypersensitivity to the drug.
Azathioprine should not be used for treating rheumatoid arthritis in pregnant women.
Patients with rheumatoid arthritis previously treatedwith alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others). Prohibitive risk of neoplasia may occur it treated with azathioprine.
ADVERSE REACTIONS
- Hematologic: Bone marrow depression manisfested by leucopenia, macrocytic anemia, pancytopeniaand thrombocytopenia. Hematologic status should be carefully monitored.
- Gastro-intestinal: Nausea, vomiting, anorexia and diarrhea may occur in patients receiving large doses of azathioprine. Adverse GI effects may be minimized by giving drug in divided doses and/or after meals. Vomiting with abdominal pain may occur rarely with a hypersensitivity pancreatitis.
-Hepatotoxicity: Manifested by increased serum alkaline phosphatase, bilirubin, and/or aminotransferase concentrations.
Skin Reaction: Drug flush, skin rash and various allergy manifestations.
Others: Infection, drug fever serum sickness, alopecia, arthralgia, retinopathy, Raynaud degree 0s disease, pulmonary edema.
PRECAUTIONS
There are potential hazards in the use of this preparation. Therefore, it should not be prescribed unless the patient can be adequately monitored for toxic effects throughout the duration of the therapy.
During the first eight weeks of therapy with azathioprine, complete blood counts, including platelet counts, must be performed at least weekly (and more frequently when higher dosages are used or in the presence of disturbed renal or hepatic function). The blood count frequency may be reduced later in the therapy.
If tolerance does not occur, azathioprine can be used for long-term administration.
In case of systemic lupus erythematosus (SLE) accompanying nephritis, azathioprine can cause severe recurrence because of administration discontinuance. Administration discontinuance should be enforved with careful observation.
Particular care should beraken to monitor serious renal and hepatic failure at the early years and to reduce the maintenance dosage.
Serious secondary infections by specific microorganism are a constant hazard on immunosuppresive treatment especially for transplant patients.
Azathioprine is mutagenic in animals and humans, carcinogenic in animals, and may increase the patient’s risk of neoplasia. Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. The risk of post transplant lymphomas may be increased in patients who receive aggressive treatment with immunosuppressive drugs.
Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in sperm viability and sperm count in mice at doses 10 times the human therapeutic dose.
DRUG INTERACTIONS
Use with Allopurinol: Increases the possibility of toxic effect of azathioprine, particularly bone bone marrow depression. When azathioprine and allopurinol are administered concomitantly, dosage of azathioprone should be reduced to 25-33% of the usual dosage, and subsequent dosage adjusted according to the patient response and toxic effects.
Use with Cytostatic agents: Azathioprine should be used with caution in patients receiving or who have recently received other bone marrow suppressive agents.
Use with Other Agents affecting Myelopoesis: Drugs which may effect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients.
Use with Angiotensin-Converting Enzyme Inhibitor: The use of angiotension-convertin enzyme inhibitors to control hypertension in patients under azathioprine treatment has been reported to induce anemia and severe leukopenia.
Use with Warfarin: Azathioprine may inhibit the anticoagulant effect of warfarin.
USE IN PREGNANT WOMEN AND NURSING MOTHER
Azathioprine is teratogenic in rabbits and mice when given in doses equivalent to the human doses(5mg /kg daily), Abormalities including skeletal malformation and visceral anomalies.
In a detail case report documented lymphopenia, diminished 1gG and 1gM levels, CMV infection, and a decreased thymic shadow where noted in an infant born to a mother receiving 150 mg azathioprine and 30 mg prednisone daily throughout pregnancy, pancytopenia and severe immune deficiency in a preterm infant whose mother received 125 mg a azathioprine adn 12.5 mg prednisone daily and an infant born with preaxial whose mother received azathioprine 200 mg daily and prednisone 20 mg mg every other day during pregnancy.
If this drug is used during pregnancy or if the patient become pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of child bearing age should be advised to avoid becoming pregnant.
OVERDOSAGE
Symptoms of overdose include nausea, vomiting, diarrhea, and 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.
The oral LD50s for single doses of azathioprine 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 protiens, but approximately 45% is removed during an 8-hour hemodialysis2. A single case has been reported of a renal transplant patient who ingested a single dose of 7.5 g azathioprine. The immediate toxic reactions were nausea, vomiting, and diarrhea, followed by mild leukopenia and mild abnormalities in liver function. The white blood cell count, SG0T, and bilirubin returned to normal 6 days after the overdose.
CAUTION
Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.
STORAGE
Store at temperatures not exceeding 30 degree Celsius.
AVAILABILITY
Foil strip to 10′s; 100 Tablets/Box.