Monday, February 9, 2015

Azathioprine (Imuran) overview in the treatment of Myasthenia Gravis

Azathioprine (Imuran) is in a class of drugs referred to as antimetabolites. Antimetabolites have a course of action that blocks the proliferation of cells. Specifically, the inhibition of T lymphocytes is the thought to be a mechanism for benefit. Research and blood tests confirm that Acetylcholine receptor antibody levels are decreased with the use of  azathioprine as a treatment for myasthenia gravis.

Often Azathioprine is used in patients who have relapsed while using prednisone or as a steroid-sparing agent in patients who have been taking
prednisone for long periods of time. Many neurologists are now starting both corticosteroids and azathioprine at the same as has been popular to do in Europe.

Research of the historical data of patience undergoing azathioprine therapy has shown 70 to 90% of MG patients improve whether the drug is used as a first- or second-line therapy. However, the response is slow, ranging from 3 to 12 months. In an important double-blind study comparing the use of oral prednisolone versus prednisolone plus azathioprine, patients receiving both medications had fewer relapses, a higher incidence of remission, and could ultimately be managed on a lower corticosteroid dose. The beneficial effects of azathioprine were not seen until after 18 months.

On the basis of this data, corticosteroids and azathioprine are often combined in the initial treatment of patients with MG. Some neurologists frequently still use prednisone monotherapy, especially in patients without risk factors for steroid-induced morbidity (e.g., obesity, diabetes, hypertension, osteopenia). This controlled study underscores the long latency before clear benefit from azathioprine may be seen. Therefore, for patients in whom a more rapid effect is needed, other treatments should be considered.

Azathioprine is started at 50 mg per day. If, after 1 week, there are no systemic side effects, the dose is increased to 2 to 3 mg/kg per day. Therefore, after the initial test dose, most MG patients are placed on 150 to 200 mg per day. Azathioprine is usually well tolerated, but there are a few limiting adverse effects. Within the first several weeks of treatment, ~10% of patients will have an idiosyncratic reaction consisting of fever, anorexia, nausea, vomiting, and abdominal pain.[17] Patients feel as if they have the flu. These symptoms resolve quickly after the drug is stopped. The same symptoms usually return if the patient is reexposed to azathioprine. Leukopenia and hepatotoxicity are important adverse effects. White blood cell counts and liver function tests should be monitored monthly.

If the white blood cell count decreases below 4000 cells/mm3, the dose should be decreased. If the count falls below 3000 cells/mm3, azathioprine should be stopped. Medication should also be held if liver enzymes become significantly increased. In these circumstances, patients can be rechallenged with azathioprine, although in many patients, recurring toxicity will require discontinuation of this drug. Following long-term use of azathioprine, patients are at increased risk of developing malignancies. Azathioprine is teratogenic and can impair fertility in women.

Source: Medscape Discussion of MG

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