Azathioprine Pharmachemie Special Precautions

Monitoring: There are potential hazards involved with the use of the medicinal product; therefore it should only be prescribed if the patients can be sufficient for toxic effects during the entire therapy.
At least once a week for the first eight weeks of the treatment a complete blood count, including thrombocytes, should be done. This needs to be done more frequently with higher doses or with severe renal and/or liver dysfunction. After this period of time the monitoring may be done in a reducing frequency and it is recommended to repeat a complete blood count monthly, or at least with intervals of no more than three months.
Patients who receive azathioprine, should be instructed to immediately report to the doctor any sign of infection; unexplained bruising, bleeding or other expression of bone marrow depression. In rare cases people have an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT). They may be unusually sensitive to the myelosuppressive effect of azathioprine and may be increased risk of developing myelotoxicity. This problem may be increased by the co-administration of TPMT inhibiting medicinal products such as: olsalazine, mesalamine or sulfasalazine.
Renal and/or hepatic insufficiency: It has been suggested that the toxicity of azathioprine would be increased in the presence of renal insufficiency, but controlled studies do not support this point of view. Nevertheless it is recommended to choose doses on the low end of the normal dose ranging scale and to carefully do the haematological check ups. The dose should be reduced further in case of the occurrence of haematological toxicity.
Caution is needed with administration of azathioprine to patients with a liver function disorder and complete blood counts and liver function tests should be done regularly. In such patients the metabolism of azathioprine may be reduced and therefore the dose of azathioprine should be reduced to the low end of the recommended dose range. The dose should be further reduced in case of the occurrence of haematological or liver toxicity.
Mutagenicity: In both male and female patients who were treated with azathioprine, chromosome aberrations have been shown, but the abnormalities were reversed following discontinuance of the drug.
Teratogenicity: Indications for teratogenicity in humans are doubtful. As is true for all treatments with cytotoxic chemotherapeutic agents, adequate contraceptive measures should be advised when one of the parents is treated with azathioprine.
Carcinogenicity: Patients receiving immunosuppressive therapy are at an increased risk of Neoplasia.
Patients receiving multiple immunosuppressive agents may be at risk of over-immunosuppression, therefore such therapy should be maintained at the lowest effective level.
Varicella zoster virus infection: Infection with varicella zoster virus (VZV; chickenpox and herpes zoster) may become severe during the administration of immunosuppressants. Caution should be exercised especially with respect to the following: Before starting the administration of immunosuppressants, the prescriber should check to see if the patient has a history of VZV. Serologic testing may be useful in determining previous exposure. Patients who have no history of exposure should avoid contact with individuals with chickenpox or herpes zoster. If the patient is exposed to ZVZ, special care must be taken to avoid patients developing chickenpox or herpes zoster, and passive immunization with varicella-zoster immunoglobin (VZIG) may be considered.
If the patient is infected with ZVZ, appropriate measures should taken, which may include antiviral therapy and supportive care.