Azathioprine and mercaptopurine

What are azathioprine and mercaptopurine?

Azathioprine is a thiopurine antimetabolite analog term Medication that suppresses the immune system by altering the function of white blood cells. It is switched in the liver to a related drug, mercaptopurine, and then to metabolites called thioguanine (thioguanine) nucleotides, which inhibit cell growth.

What skin disorders are azathioprine and mercaptopurine used for?

The main cutaneous The indications for azathioprine and mercaptopurine are:

• Systemic lupus erythematosus
• Dermatomyositis
• Pemphigus vulgaris

• Cutaneous polyarteritis nodosa.

Other skin disorders treated with these medications include:

• Atopic dermatitis (eczema)
• Bullous pemphigoid
• Pyoderma gangrenous
• Cutaneous lupus erythematosus

• Cutaneous vasculitis.

What doses are used?

In New Zealand, azathioprine is available as 50 mg tablets or as an injection, brand name Imuran®, Azamun®, Imuprine. Mercaptopurine is available in 10mg or 50mg tablets, brand name Puri-nethol®. The dose is generally one or two tablets once or twice a day (1–3 mg / kg / day). Occasionally, doses of up to 5 mg per kg of body weight per day are needed.

What are the side effects and risks of azathioprine and mercaptopurine?

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

• Loss of appetite, nausea, vomiting, or diarrhea (more common if medications are taken on an empty stomach). Mouth ulceration It can also happen.
• Liver discomfortcholestatic hepatitis) Hypersensitivity The reaction to azathioprine generally affects the liver, most often several weeks after starting treatment.
• Pancreatitis
• Lung disease: acute interstitial pneumonia, eosinophilic pneumonia or chronic pneumonitis
• Suppression of the bone marrow, particularly leukopenia (reduced number of white blood cells); azathioprine should be discontinued if the neutrophils the count falls below 1.0 × 10 ^ 9 / L, the lymphocyte the count falls below 0.5 × 10 ^ 9 / L or the platelet counts below 50 × 10 ^ 9 / L.
• Megaloblastic erythropoiesis or macrocytosis (production of large red blood cells).
• Prolonged severe drug hypersensitivity syndrome Resulting in extended eruption, fever, enlarged lymph nodes and organ failure (heart, lungs, kidneys, liver).
• Hair lost
• Immunosuppression leads to an increased risk of serious infections.

• Skin Cancer, especially cutaneous scaly cell carcinoma. This is more likely after several years of azathioprine treatment, especially on skin that has been exposed to the sun. Protect your skin from the sun at all times, using a broad-spectrum sunscreen on exposed areas every day.

Azathioprine and mercaptopurine are FDA category D pregnancy. When possible, these medications should not be taken during pregnancy, except when the benefits outweigh the risks. Those taking these medications should not breastfeed. In some circumstances, it may also be advisable for men to ensure that their partners do not become pregnant, but it is generally believed that azathioprine does not affect fertility in men. Discuss your own situation with your doctor.

Prevention of infection when you take azathioprine or mercaptopurine

Evidence to exclude latent Tuberculosis and Hepatitis B / C are wise before starting azathioprine and for determining immunity against measles and chicken pox. It is also important to consider the need to update immunization in immunosuppressed dermatology patients

Monitoring while taking azathioprine or mercaptopurine

Patients taking azathioprine or mercaptopurine should be closely monitored and regular blood tests should be performed to monitor the safety of the treatment, first biweekly and then monthly long term.

• Complete blood count (CBC or FBC)
• Liver function tests

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

Thiopurine methyltransferase (TPMT) levels can be measured to determine the 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 1 mg / 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 if the dose is correct.

Patients taking azathioprine and mercaptopurine should also have regular skin checks and self-exams.

Pharmacological interactions with azathioprine and mercaptopurine

If you take azathioprine, you should inform any doctor or pharmacist. It is particularly important if you are taking allopurinol for gout since the azathioprine dose should be reduced from a quarter to a third of the normal amount to avoid toxicity.

It is best to avoid the following medications, but if it is unavoidable, it is important to monitor your blood count very carefully:

• • Neuromuscular blocking agents (such as rocuronium, mivacurium, vecuronium, atracurium, tubocurarine)
  • Warfarin (warfarin dose requirement may increase 3 to 4 times during azathioprine treatment)
  • D-penicillamine
  • Trimethoprim + sulfamethoxazole
  • Captopril, enalapril, lisinopril and other angiotensin converters enzymes Inhibitors (ACE)
  • Cimetidine
  • Indomethacin

• Sulfasalazine and other derivatives of benzoic acid.

• Live vaccines like yellow fever.