Improper Potency and Impurities in Compounded Polidocanol
November 2019 | Volume 18 | Issue 11 | Original Article | 1124 | Copyright © November 2019
Margaret Mann MD,a Gilly S. Munavalli MD,b Lisa Amatangelo MD,c and Nick Morrison MDd
aInnova Dermatology, Hendersonville, TN bDermatology, Laser & Vein Specialists of the Carolinas, Charlotte, NC cWeill Cornell Vein Treatment Center, New York, NY dCenter for Vein Restoration, Mesa, AZ
Polidocanol is an FDA-approved sclerosant indicated for treating uncomplicated spider veins and reticular veins in the lower extremities. Despite restrictions against compounding drugs that are essentially copies of FDA-approved or commercially available products, polidocanol is also available from compounding pharmacies and outsourcing facilites. Compounded drug products are not FDA-approved and have not undergone premarket FDA review for safety, effectiveness, and quality. Seven samples of polidocanol were obtained from three compounding pharmacies and analyzed using high pressure liquid chromatography. None of the samples contained the labeled concentration of polidocanol and five contained excessive levels of impurities. Since the potency and purity of compounded polidocanol injection cannot be assured, physicians who use these products should consider FDA-approved products to ensure optimal safety and efficacy. J Drugs Dermatol. 2019;18(11):1124-1127.
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Varicose veins are enlarged superficial veins, most commonly found in the lower extremities. Risk factors include family history, advancing age, female gender, pregnancy, obesity and sedentary lifestyle.1 Spider veins are similar, but they are smaller, more superficial and often red or blue. Some varicose veins become symptomatic and require treatment. Symptoms may include burning, throbbing, muscle cramping, itching, and edema. Depending on their size and severity, treatments for varicose veins include compression,2 energy-based radiofrequency3 and laser devices,4 a variety of surgical procedures,5 and sclerotherapy.6 Sclerotherapy involves injecting a sclerosant into the lumen of a vein, resulting in fibrosis and eventual vein ablation.7 Despite the increased popularity of new cutaneous laser devices, sclerotherapy remains the gold standard for treatment of reticular varicose and spider veins,15,16 especially since FDA-approval of sclerosant agents in 2010.19,20
Available FDA-approved liquid sclerosing agents include sodium tetradecyl sulfate and polidocanol.8 Polidocanol was first approved for use as a sclerosing agent in the United States in 2010 (Asclera® Injection, Merz North America, Raleigh NC).9 Specifically, this drug product is indicated to sclerose uncomplicated spider veins (varicose veins ≤1 mm in diameter) and uncomplicated reticular veins (varicose veins 1 to 3 mm in diameter) in the lower extremities. Polidocanol is also an approved sclerosing agent in Europe (Aethoxysklerol®, Chemische Fabrik Kreussler & Co. GmbH, Wiesbaden, Germany). The safety and efficacy of polidocanol as a sclerosant have been demonstrated in large trials.21 Polidocanol is also available from certain compounding pharmacies and outsourcing facilities, despite government restrictions on compounding drugs that are “essentially copies” of FDA-approved or commercially available products.10 Compounded drug products are not FDA-approved and have not undergone FDA premarket review for safety, effectiveness, and quality. Of note, polidocanol is manufactured according to strict FDA regulations for purity and potency throughout the entire manufacturing process. Unlike pharmaceutical companies, compounding pharmacies and outsourcing facilities are not required to report adverse events to the FDA.11 Despite FDA restrictions for compounding drugs, polidocanol remains available from compounding pharmacies and outsourcing facilities, potentially exposing patients to potentially serious health risks.
Previous investigations have demonstrated the inferiority of compounded sclerosants. Among compounded products in one study, three did not contain the labeled drug concentration: two were super-potent, one was sub-potent and all contained impurities.12 These products were believed to be made by diluting the active substance from industrial chemical sources. In another study, five of six samples obtained from three pharmacies did not contain the labeled drug concentration, exceeding it by 20% to 300%, and all six contained impurities.13 In a third study, chemical impurities were measured in eight of nine compounded samples from three pharmacies and some contained unknown particulate matter, while no impurities were detected in the original FDA-approved product.14