As compounded polidocanol for the treatment of varicose
veins continues to be available from several pharmacies and
outsourcing facilities in the United States, the objective of
this study was to obtain and analyze samples of compounded
polidocanol for potency and purity.
Seven samples of polidocanol were purchased from three
compounding pharmacies. Labeled concentrations of
polidocanol ranged from 1.5% to 5%. Each sample was analyzed
for potency of lauromacrogol 400 (polidocanol) and purity with
reversed phase high pressure liquid chromatography (HPLC)
with refractive index (RI) detection (Chemische Fabrik Kreussler
& Co. GmbH, Wiesbaden, Germany). The results were compared
with an FDA-approved polidocanol product (Asclera® Injection,
Merz North America, Raleigh NC).
Results of the analysis are summarized in Table 1. Among the
seven samples analyzed, six were sub-potent, containing 65.8 to
91.4% of the labeled concentration, and one was super-potent,
containing 108.7% of the labeled concentration. Five contained
a 10-fold excess of foreign fatty alcohol ethoxylate impurities
and four exceeded the limit for unknown impurities. Overall,
none of the tested samples were equivalent to the commercially
marketed, FDA-approved product (Asclera) with respect to
potency and purity.
Similar to previous studies,12,13 compounded polidocanol solutions did not deliver the claimed potency in six of seven tested samples and five samples contained excessive contaminants. This inconsistency poses unacceptable risks, most importantly to the patient, but also medicolegal risks to the treating physician. In contrast, clinical trials have demonstrated FDA-approved polidocanol provides effective treatment of chronic venous insufficiency with low toxicity, minimal risk and few complications.21
Contaminants found in the tested compounded polidocanol samples in several publications included foreign fatty C-14 alcohol ethoxylate impurities, excessive formaldehyde and unknown impurities. Other reported contaminants in compounded sclerosants include carbitol,12 tetradecanol, several isomers of 7-ethyl-2-methyl-undec-3/4 ene,14 chlorobutanol (trichloro-2- methyl-2-propanol), benzaldehyde, and benzyl alcohol13 (some samples contained multiple contaminants). Together, these results indicate the lack of purity of the ingredients and/or the absence of sufficient manufacturing controls used to compound these products.
In addition to frequently not meeting the labeled ingredient specifications for potency and purity, there is no requirement for compounded product labeling to include an approved shelf life. If the compounded product is not immediately used, there is no assurance that the product will remain potent and efficacious.