Accuracy and precision of compounded ciclosporin capsules and solution

The prescribing of compounded products that mimic US Federal Drug Administration approved drugs in the USA is inappropriate. Among the reasons are the lack of premarket regulatory assessment and the potential for an inferior product. This study describes the accuracy and precision of ciclosporin (CsA) strength when compounded as capsules (10 and 300 mg) and solutions (50 and 150 mg/mL).

Preparation choices reflected current prescribing practices. Each was acquired by prescription from five pharmacies at three different times, 14-45 days apart. Atopica(®) (10 and 100 mg; Novartis, Greensboro, NC, USA) and three human generics (50 and 100 mg capsules and 100 mg/mL solution) were positive controls. Physical characteristics were assessed. Accuracy (percentage predicted) was based on CsA strength measured by high-performance liquid chromatography and precision was based on replications (n = 3) from each pharmacy.

Accuracy of positive controls ranged from 92 to 103%. For compounded solutions, physical characteristics differed markedly between but not within pharmacies. Capsule accuracy was 10 ± 0.98 mg (101%) for 10 mg and 290 ± 9.6 mg (97%) for 300 mg; and solution accuracy was 45 ± 9.9 mg/mL (90%) for 50 mg/mL and 127 ± 18 mg/mL (85%) for 150 mg/mL. The precision for 50 mg/mL oral solution was 0.67-11%, and for 150 mg/mL, 3.7-14%. Accuracy for all preparations varied, with the least accurate deviating by 34% from labelled strength. Precision for all capsules ranged from 0.6 to 8.7%.

Compounded CsA solutions may deviate by more than 10% from the labelled strength. Bioavailability and clinical efficacy of compounded CsA remain unknown, and such products should be prescribed only in appropriate circumstances.