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Introduction to dermatological treatment
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
Azathioprine is used for atopic and photosensitive eczema, and as a steroid-sparing drug in pemphigus, pemphigoid, dermatomyositis and SLE. It is given at a dose of 1–3 mg/kg/day, usually 50-100 mg b.i.d. Before starting check the thiopurine methyltransferase (TPMT) level (normal 25–50, carrier 10–25, deficiency <10 pmole/l/mg Hb), since if it is low, there is an increased risk of myelosuppression. It takes 6–8 weeks before there is any effect so it is no good as a first line treatment in patients with pemphigus and pemphigoid. The patient can be started on azathioprine at the same time as the steroids; after 6–8 weeks, when the azathioprine will have begun to work, the dose of steroid is gradually reduced.
Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Interestingly, the immunosuppressant agent azathioprine (ImuranTM) is a prodrug of 6-mercaptopurine and is metabolized to the active form. Azathioprine has been used experimentally in the treatment of cancers such as childhood leukemia and lymphomas in adults, but it is now used mainly for autoimmune conditions (e.g., Crohn’s disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and other connective tissue disorders, polymyositis severe refractory eczema, and generalized myasthenia gravis), particularly when corticosteroid therapy alone fails to provide inadequate control, and for suppression of organ transplant rejection.
Other Immunosuppressive Agents in Vitiligo
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Azathioprine is an immunosuppressive agent which is widely used in autoimmune disorders. It has a good safety profile and is also more cost effective. Its use in vitiligo is limited. It has been tried as combination therapy with oral PUVA and compared with oral PUVA therapy alone. Azathioprine was given at a dose of 0.6–0.75 mg/kg (max dose 50 mg per dose). After a follow-up for 4 months, 58.4% body surface repigmentation was seen in the azathioprine and PUVA therapy combination group, while only 28.4% repigmentation was seen in the PUVA therapy only group. Repigmentation of the acral areas was better in the azathioprine only group while perifollicular repigmentation was earlier in the azathioprine and PUVA combination group. Two patients developed gastric upset while on azathioprine. This was the only side effect seen [11].
Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists
Published in Seminars in Ophthalmology, 2022
Antimetabolites act by inhibition of nucleic acid synthesis, thereby inhibiting cell proliferation.13 Azathioprine is a purine nucleoside, which suppresses the synthesis of inosinic acid, thereby interfering with the DNA replication and RNA transcription.4 The percentage of patients achieving corticosteroid-sparing success following azathioprine use is reported to be lower than other antimetabolites.14–17 Other disadvantages include a higher discontinuation rate due to gastrointestinal intolerance, bone marrow suppression and hepatotoxicity.1,4,11 However, bone marrow suppression is uncommon at low doses, and as such, is reversible. The recommended dose for azathioprine is 1–3 mg/kg/day (maximum recommended dose is 2.5 mg/kg/day).4 A complete blood count (CBC) should be performed every month and liver function tests (LFTs) should be performed every 3 months. If liver enzyme levels are >1.5 times the upper limit of normal, the dose should be decreased by 25–50 mg/day and the repeat LFTs done in 2 weeks.4
An update on the pharmacological management of autoimmune hepatitis
Published in Expert Opinion on Pharmacotherapy, 2021
Yooyun Chung, Mussarat N Rahim, Jonathon J Graham, Yoh Zen, Michael A Heneghan
At least 10–20% of the patients will have insufficient response or intolerance to first-line therapy. Insufficient response is defined as incomplete biochemical remission after 6 months of treatment. In the first instance, measuring the azathioprine metabolites, 6-TGN and 6-MMP, will guide dose optimization or adjunctive therapy with allopurinol. Low 6-TGN and low 6-MMP levels can be ameliorated by increasing the azathioprine dose. Low 6-TGN and high 6-MMP levels can be optimized with use of allopurinol (100 mg/day) to reduce 6-MMP production. This strategy requires the azathioprine dose to be reduced by 75% to prevent toxicity from increased 6-TGN production [31]. Low 6-TGN and 6-MMP levels despite dose adjustments may indicate noncompliance to thiopurine treatment. Azathioprine side effects include gastrointestinal symptoms. If a patient is intolerant of azathioprine, changing to MP is a reasonable first step as it is as effective as azathioprine and can be better tolerated in the context of gastrointestinal side effects [32].
Efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn’s disease
Published in Scandinavian Journal of Gastroenterology, 2021
Bing-xia Chen, Ze-min Han, Qian Zhou, Hong-bin Liu, Pei-chun Xu, Fa-chao Zhi
Azathioprine was administered in combination with infliximab. During the treatment course, azathioprine-induced adverse events occurred in 13 patients, of which 11 had non-dose related adverse events (6 with nausea or vomiting and 5 with flu-like symptoms such as malaise, fever, muscle pain and joint pain) and 2 had dose-related adverse events (leucopenia). As suggested by Green and Mee [19], azathioprine was recommenced at a low dose, gradually building up to a therapeutic dose in those with non-dose related adverse events. Finally, 9 of the 13 patients were able to tolerate a full dose of azathioprine, and the other 4 patients discontinued azathioprine due to intolerance. Because the number of patients intolerant to azathioprine was too small to draw a reliable conclusion on the impact of azathioprine intolerance on patients’ outcomes, the factor ‘azathioprine intolerance’ was not introduced in the Cox regression model in the later section of this article.