Azathioprine

Registered South African indications:

• Prevention of rejection of organ and tissue transplantation
• Autoimmune disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Severe hepatic impairment
• Elderly
• Inherited deficiency of the enzyme thiopurine methyltransferase
• Hypoxanthine-guanine-phosphoribosyltransferase deficiency 
• Exposure to sunlight and ultraviolet light
• History of infection with varicella zoster virus

Forms avail. in SA and covered in this monograph: tab, inj

Prevention of rejection of organ and tissue transplantation (additional agent required)

• IV/Oral (tab): Loading dose: 1-5mg/kg/day; Maintenance: 1-4mg/kg/day after transplantation

Autoimmune diseases
- Severe rheumatoid arthritis
- Systemic lupus erythematosus
- Auto-immune active chronic hepatitis
- Pemphigus vulgaris
- Auto-immune haemolytic anaemia
- Idiopathic thrombocytopenic purpura
when these conditions are refractory to corticosteroids or controlled by corticosteroids in dosages which are producing severe side-effects

• IV/Oral (tab): 1-2.5mg/kg/day

- Active chronic hepatitis

• IV/Oral (tab): 1-2mg/kg/day

Do not cut/crush/chew/dissolve

Injections may be given for a short period if patients unable to take oral medication; but tablets should be substituted as soon as possible

If no discernible improvement occurs in the patient's condition within three months, consideration should be given to the withdrawal of the drug

Treatment is otherwise undertaken on a long-term basis unless the patient exhibits evidence of intolerance to azathioprine

See additional prescribing points 

No information available

Pregnancy

• Caution, positive evidence of risk
• Substantial transplacental and transamniotic transmission of azathioprine and its metabolites from the mother to the foetus have been shown to occur. Azathioprine should not be given to patients who are pregnant or likely to become pregnant in the near future without careful assessment of risk versus benefit
• Evidence of the teratogenicity of azathioprine in man is equivocal. As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving azathioprine. There have been reports of premature birth and low birth weight following maternal exposure to azathioprine, particularly in combination with corticosteroids. There have also been reports of spontaneous abortion following either maternal or paternal exposure. Leucopenia and/or thrombocytopenia have been reported in a proportion of neonates whose mothers took azathioprine throughout their pregnancies

Breastfeeding

• Caution; not recommended
• 6-Mercaptopurine has been identified in the colostrum and breast milk of women receiving azathioprine treatment. It is recommended that mothers receiving azathioprine should not breastfeed

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• Mild to moderate (Child-Pugh Class A and B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; dose adjustment recommended
  Repeat liver function tests every 3 months
  If LFT abnormalities are observed (ALT more than X3 ULN): Reduce dose by 0.5 mg/kg (approx. 25 mg daily) every 4 weeks until the lowest effective dose is reached
  Monitor for delayed toxicities

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Respiratory Disorders

• Reversible pneumonitis

Gastrointestinal Disorders

• Pancreatitis
• Colitis
• Diverticulitis 
• Bowel perforation 
• Severe diarrhoea
• Pancreatitis 

Hepatobiliary Disorders

• Cholestasis 
• Degeneration of hepatic function tests
• Life-threatening hepatic damage

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Neoplasms
• Lymphoproliferative disorders
• Skin cancers 
• Sarcomas 
• Uterine cervical cancer in situ
• Acute myloid leukaemia 
• Myelodysplasia
• Non-Hodgkin's lymphomas 
• Skin cancers 
• Depression of bone marrow function
• Leucopenia
• Thrombocytopenia
• Anaemia
• Agranulocytosis
• Pancytopenia
• Aplastic anaemia
• Megaloblastic anaemia
• Erythriod hypoplasia
• Megaloblastic bone marrow changes
• Hypersensitivity reactions
• Stevens-Johnson syndrome 
• Toxic epidermal necrolysis

• Allopurinol
• Oxipurinol 
• Thiopurinol
• Neuromuscular blocking agents
• Warfarin
• Cytostatic agents
• Captopril
• Aaminosalicylate derivatives
• Furosemide 
• Live vaccines

• Full blood count with differential
• Hepatic function
• Renal function

Specific cases may require

• Dermatology examination
• Thiopurine methyltransferase genotyping

Administration directions

• IV: Reconstituted by the addition of 5-15ml Water for Injection. Given slowly, preferably by injecting it into the tubing of an intravenous saline or glucose-saline drip while the fluid is being infused
• Where dilution is not practicable, the reconstituted solution should be injected slowly over a period of not less than one minute and followed immediately by not less than 50ml of one of the recommended infusion solutions

Azathioprine, a derivative of 6-mercaptopurine, is a purine antimetabolite with immunosuppressive properties. Azathiaprine is cleaved by nucleophils such as glutathione, to 6 mercaptopurine, which in turn can be converted into 60 mercaptopurine nucleotides. These nucleotides lead to an inhibition of de novo purine synthesis.

Tablet 50mg

• Azapress (Pharmacare)
• Azathioprine 50 PCH (Teva Pharmaceuticals)
• Azamun ( Acino Pharma)
• Azuman (Pharmaplan)
• Imuran (Pharmacare)
• Zaprine (Sandoz)

Injection (per vial) 50mg

• Imuran (GSK) originator