Methimazole-Induced Agranulocytosis in Patients with Graves' Disease Is More Frequent with an Initial Dose of 30 mg Daily than with 15 mg Daily

Abstract

It is very likely that MMI-induced agranulocytosis occurs with a larger dosage of MMI and is dose related. Considering both the effectiveness and the risk of serious side effects, we recommend 15 mg/d of MMI as the starting dosage for the treatment of Graves' disease.

Antithyroid Drug-induced Agranulocytosis Complicated by Pneumococcal Sepsis and Upper Airway Obstruction

“…However, in this case, it took seven days for the patient to recover from neutropenia, even after receiving G-CSF, another finding that supports our contention that the agranulocytosis preceded the pneumococcal bacteremia. Agranulocytosis usually occurs within two months of the initiation of ATD therapy (8) and is more likely to develop in older patients (>40 years of age) (9) and those receiving higher doses of MMI (30 vs. 15 mg/day) (10). In the present young patient, agranulocytosis developed nine months after the administration of 30 mg/day of MMI; therefore, we believe that the higher dose may have played a role in the pathogenesis of agranulocytosis in this case.…”

Agranulocitosis inducida por metimazol en pacientes con enfermedad de Graves

“…En un estudio retrospectivo de casi 6 000 pacientes, se encontró mayor frecuencia de AIM en los pacientes que recibieron MMI 30 mg/día, en comparación con los que recibieron MMI 15 mg/día (0,814% vs. 0,219%, p< 0,01) (8). Otro estudio encontró que la AIM fue 11 veces más frecuente en el grupo que recibió 30 mg/día (6).…”

Agranulocytosis Developed After Dose Escalation in a Patient Under Chronic Methimazole Treatment

“…However, many studies have supported conclusion that development of agranulocytosis is dose dependent. [2][3][4] Our patient had been using methimazole for 3 years, and agranulocytosis developed after escalation of methimazole dose. Strikingly, neutropenia developed 5 days after dose increase.…”

“…However, there have been cases reported in which condition developed in early period, as early as 6 days of drug use, or in the long-term, 1 or 2 years after onset of drug therapy. [2,3] Antithyroid drugs easily penetrate bone marrow and typically exert their toxic effect 20-40 days after drug exposure. However, many studies have supported conclusion that development of agranulocytosis is dose dependent.…”