Colchicine Intolerance: Does the Pharmaceutical Preparation Matter?

To the Editor,

Recently, 3 observational studies, one in adult[1] and 2 in the pediatric population,[2,3] were published regarding the efficacy of different pharmaceutical colchicine preparations in familial Mediterranean fever (FMF). It was consistently shown that patients resistant to sugar-coated tablets might benefit from compressed colchicine tablets, and this was explainable by different pharmacokinetic properties of the preparations.[1] Moreover, resistant and intolerant patients to sugar-coated tablets may benefit from the compressed ones, as shown by Türkuçar et al. in their study in the pediatric population published in the January 2021 issue of the Balkan Medical Journal.[3] Intolerance to colchicine, mostly due to diarrhea, is a major barrier to increase the dose to a level adequate to control the attack frequency. We want to share our experience of compressed colchicine tablets in adult FMF patients intolerant to sugar-coated tablets.

Fourteen patients, older than 18 years of age, followed up in 3 centers in Turkey (Liv Hospital, Ankara, Yıldırım Beyazıt University Atatürk Training and Research Hospital, Ankara & Trakya University Hospital, Edirne) from 2015 to 2020, with a clinical diagnosis of FMF meeting Tel Hashomer criteria[4] and under treatment with Colchicine opocalcium® (Mayoly Spindler, France), a compressed colchicine preparation, due to intolerance to sugar-coated tablets (Colchicum-Dispert®, Recordati, Turkey & Kolsin®, İbrahim Etem Ulagay, Turkey), were identified and included in the study. Patients under anti-interleukin 1 or other biological agents were excluded.

Eight (57.1%) were females, and the median age and disease duration was 32 (range: 21-44) and 8 (range: 2.5-18) years, respectively. Attack characteristics and MEditerranean FeVer (MEFV) gene mutation profile were provided in Figure 1. All patients had diarrhea, defined as 3 or more loose/liquid stools per day, with sub-optimal doses of sugar-coated colchicine tablets, and none had diarrhea under the compressed tablets. The frequency of the attacks significantly decreased after the pharmaceutical change (Figure 1 a-c), although the daily colchicine doses were similar (1.5 ± 0.25 and 1.56 ± 0.52 mg/day before and after the pharmaceutical change, respectively). Median duration under the sugar-coated and compressed tablets was 5 (range: 0.5-10) and 2.5 (range: 1-8) years.

FIG. 1.

Clinical features. (a-c). Attack characteristics (a) and MEditerranean FeVer (MEFV) gene mutation profile (b) of the patients. Note that the number of attacks decreased significantly after the pharmaceutical change (c). *Wilcoxon signed-rank test.

As a major limitation, this study was not a head-to-head comparison of different pharmaceutical preparations of colchicine and did not involve patients intolerant to the compressed colchicine tablets. The patient group was also small. But it was evident that some FMF patients intolerant to the sugar-coated tablets may benefit from the compressed colchicine tablets. In this subgroup of patients, the treatment seems sustainable.