Azathioprine, 6-MP
9,611 views
Oncology Pharm
- Bleomycin
- Dactinomycin, Actinomycin D
- Doxorubicin, Daunorubicin
- Azathioprine, 6-MP
- Cladribine
- Cytarabine
- Busulfan
- Cyclophosphamide, Ifosfamide
- Nitrosoureas
- Paclitaxel
- Vincristine, Vinblastine
- Cisplatin, Carboplatin, Oxaliplatin
- Etoposide, Teniposide
- Irinotecan, Topotecan
- Bevacizumab
- Erlotinib
- Cetuximab, Panitumumab
- Imatinib, Dasatinib
- Rituximab
- Bortezomib, Carfilzomib
- Trastuzumab
- Dabrafenib, Vemurafenib
- Raloxifene and Tamoxifen
- Hydroxyurea
- Procarbazine
Summary
Azathioprine is an antimetabolite drug used as an immunosuppressive to prevent organ rejection after transplant and to treat steroid-refractory inflammatory conditions. Azathioprine is activated to become 6-MP, which is then further metabolized by HGPRT to form purine analogs that can be incorporated into DNA and RNA and terminate synthesis. 6-MP is degraded by xanthine oxidase, and xanthine oxidase is inhibited by the gout drugs allopurinol and febuxostat. Therefore, gout patients taking azathioprine along with one of those medications can have 6-MP buildup to toxic levels. Additionally, patients on azathioprine may develop myelosuppression and GI and liver toxicity.
Key Points
- Azathioprine / 6-MP
- Mechanism
- Purine analog
- Activated by HGPRT
- Azathioprine → 6-MP → [HGPRT] 6-TGNs
- Degraded by xanthine oxidase
- 6-MP → [XO] degradation
- Activated by HGPRT
- Purine analog
- Clinical Use
- Immunosuppression
- Can be used to prevent organ rejection
- Inflammatory conditions such as RA, IBD, SLE
- Used to take patients off steroids in chronic disease and to treat steroid-refractory chronic disease
- Immunosuppression
- Adverse effects
- Allopurinol and febuxostat increase toxicity
- 6-MP is degraded by xanthine oxidase, which these drugs inhibit
- Pancreatitis
- Myelosuppression (obvious / non-specific)
- GI and liver toxicity (non-specific)
- Allopurinol and febuxostat increase toxicity
- Mechanism