(and dosage form)
Each tablet contains 50 mg Azathioprine.
A.26 Cytostatic agents
Azathioprine the imidazolyl derivative of mercaptopurine is readily absorbed after oral ingestion and is distributed throughout the body. Most of the drug is slowly metabolised to mercaptopurine but up to 10% is excreted unchanged in the urine. About one half of a dose is excreted in the urine within 24 hours as mercaptopurine and other metabolites.
Azathioprine is an antipurine immunosuppressant and antineoplastic agent with similar actions to those of mercaptopurine to which it is slowly converted in the body. Its effects appear within 2 to 4 days of administration.
Azathioprine is mainly used as an immunosuppressant for facilitating the survival of organ and tissue transplants.
Azathioprine is contra-indicated in patients with a known hypersensitivity towards it. Due to its immunosuppressant activity azathioprine should not be given to patients with acute infections.
Its use is contra-indicated during pregnancy, especially during the first trimester and should not be used in mothers who are breast-feeding.
The use of live vaccines is contra-indicated, and the response to all vaccines is likely to be diminished in patients on azathioprine.
DOSAGE AND DIRECTIONS FOR USE:
The effects of azathioprine and its active metabolite, mercaptopurine, may persist after clearance is complete and therefore it is important to reduce or withdraw the medication at the first sign of an abnormally large fall in the leucocyte count or other evidence of bone marrow depression. Renal dysfunction may result in slower elimination. Therefore the dosage should be appropriately adjusted.
The dose for immunosuppression in transplantation varies from 1 to 5 mg per kg body mass daily and depends partly on whether other drugs such as corticosteroid or radio-therapy are employed at the same time. The dose is usually increased if there is incipient rejection of the graft, but large fluctuations in dosage should be avoided. About one-half of the dose may be adequate for maintenance therapy.
For Auto-immune Disease:
Dose as prescribed.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Dose-related bone-marrow depression may be manifested as leucopenia or thrombocytopenia, or less often anaemia, and may occasionally be delayed.
Macrocytic, including megaloblastic, anaemia has occurred.
Azathioprine has been associated with the development of liver damage. It has been suggested that cholestatic symptoms may be due to the mercaptopurine moiety.
Rarely, delayed and potentially fatal veno-occlusive liver disease has occurred.
Other side-effects associated with azathioprine include gastro-intestinal disturbances, reversible alopecia, and symptoms including rashes, muscle and joint pains, fever, rigors, pneumonitis, pancreatitis, meningitis, arrhythmias, renal dysfunction and hypotension, some or all of which may represent hypersensitivity reactions.
Antineoplastic chemotherapy may lead to suppression of ovarian and testicular function resulting in amenorrhoea and the inhibition of spermatogenesis.
Gynaecomastia has been reported. The majority of antineoplastic agents are potentially mutagenic and teratogenic.
Other adverse effects occurring with antineoplastic agents include hyperuricaemia and acute renal failure due to uric acid nephropathy.
Hyperphosphataemia and other disturbances of electrolyte balance have also been reported. Pigmentation of the skin and nails occurs with several antineoplastic agents and may occasionally be part of Addisonian syndrome. Jaundice and abnormal liver function tests may sometimes be a manifestation of the disease rather than its treatment. Effects on the lung, culminating in pulmonary fibrosis, and neurotoxicity, both central and peripheral, occur variably.
These agents should only be used as immunosuppressants in life-threatening situations. Immunosuppression and bone-marrow depression are common features of these agents and their use is associated with an increased risk of infections caused by pathogenic bacteria or opportunistic micro-organisms including fungi, viruses and protozoa, and a reduced capacity to cope with them. Blood counts and measurement of haemoglobin concentrations should be carried out routinely to help predict the onset of bone-marrow depression. Antineoplastic agents should be given with extreme caution when the marrow is already depressed following radiotherapy or therapy with other antineoplastic agents.
Azathioprine should be used with care in patients with liver damage or a history of liver disease. If infection develops during treatment, azathioprine should be withdrawn.
The effects of azathioprine are enhanced by allopurinol and the dose of azathioprine should be reduced to one-third to one-quarter when allopurinol is given concomitantly. Reduced doses may be required in patients with impaired renal function.
Severe bleeding occurred in a patient on long-term warfarin treatment after discontinuing azathioprine.
Antagonism of the neuromuscular blocking effects of competitive neuromuscular blockers has been reported with azathioprine.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Nausea, vomiting, diarrhoea, anorexia, and severe bone marrow depression. Treatment is symptomatic. Anti-emetic therapy should be given in an attempt to prevent or control nausea and vomiting.
A pale yellow, biconvex, bisected tablet.
Packs of 100 tablets.
Store below 25°C.
Keep container tightly closed and protect from light.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
BODENE (PTY) LIMITED trading as Intramed
6 Gibaud Road
Port Elizabeth 6001
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
A & S PRINTERS
Updated on this site: April 2002
Source: Hospital Pharmacy
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