Azathioprine and mercaptopurine

Author: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, 2001.

What are azathioprine and mercaptopurine?

Azathioprine is a thiopurine analogue drug that suppresses the immune system by altering white blood cell function. It is changed in the liver to a related drug, mercaptopurine and then into metabolites called thioguanine (tioguanine) nucleotides, which inhibit cell growth.

What skin disorders are azathioprine and mercaptopurine used for?

Azathioprine and mercaptopurine are used in a number of severe skin disorders including:

What doses are used?

In New Zealand azathioprine is available as 50mg tablets or as an injection, trade name Imuran®, Azamun®, Imuprine. Mercaptopurine is available as 10mg or 50mg tablets, trade name Puri-nethol®. The dose is generally one or two tablets once or twice daily (1 to 3 mg/kg/day). Occasionally doses as high as 5mg per kg body weight per day prove necessary.

Side effects and risks of azathioprine and mercaptopurine

Side effects are generally mild but occasionally are severe enough to stop treatment with azathioprine or mercaptopurine.

Azathioprine and mercaptopurine are FDA Pregnancy Category D. Where possible, these drugs should not be taken during pregnancy, except where the benefits outweigh the risks. Those taking these medications should not breast feed. In some circumstances it may also be advisable for males to ensure their partners do not become pregnant, but overall it is thought that azathioprine does not affect fertility in males. Discuss your own situation with your physician.

Prevention of infection when on azathioprine or mercaptopurine

Tests to exclude latent tuberculosis and hepatitis B/C are wise before starting azathioprine, and to determine measles and varicella immunity. It is also important to consider need to update immunisation in immunosuppressed dermatology patients.

Monitoring while on azathioprine or mercaptopurine

Patients taking azathioprine or mercaptopurine should be carefully monitored, and should have regular blood tests to monitor the safety of treatment, at first fortnightly then monthly long term.

Azathioprine and mercaptopurine are not metabolised properly by some people, who have a faulty enzyme called thiopurine methyltransferase. They may have one gene for the bad enzyme (found in 11% of the population) or two bad genes (in 0.3%). Those with both genes are at severe risk of dangerous marrow suppression i.e. reduction of white cells (leucopaenia) or of all blood cells (pancytopaenia). Some other individuals have high levels of enzyme activity and may require a higher dose than normal for therapeutic effect.

Thiopurine methyltransferase (TPMT) levels can be measured to determine a patient's level of risk before starting treatment. Low levels are < 5 U/mL, intermediate levels are 5-13.7 U/mL, and high levels are > 13.8 U/mL. A typical therapeutic dose of azathioprine is 1mg/kg/day when the TPMT level is 10 U/mL and 3.5 mg/kg/day when it is 20 U/mL.

6-Thioguanine nucleotide levels are sometimes used to check whether the dose is correct.

Drug interactions with azathioprine and mercaptopurine

If you take azathioprine, you must advise any medical practitioner or pharmacist. It is particularly important if you take allopurinol for gout, as the dose of azathioprine will need to be reduced to one-quarter to one-third of normal to avoid severe toxicity.

The following drugs are best avoided, but if unavoidable it is important to monitor blood count very carefully:

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