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

The Federal Food, Drug, and Cosmetic Act requires that all FDAapproved drugs must be safe and effective and manufactured according to current good manufacturing practices (GMPs) to ensure their identity, strength, quality, and purity;22 however, some pharmacies are compounding drugs that are essentially copies of approved medications and doing so outside of GMPs. According to the FDA, “Compounding is a practice in which a licensed pharmacist, a licensed physician, or in the case of an outsourcing facility, a person under the supervision of a licensed pharmacist, combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an individual patient.” The FDA has created provisions to allow the practice of compounding for individual patient needs when a drug product is not commercially available. This is common in dermatology practice for therapies such as topical anesthetic (BLT) or an acne cream, but these provisions are not applicable for an injectable product for which the FDA-approved product is medically suitable for a patient. Compounding pharmacies are advertising for physicians to use or switch to compounding sclerosant(s) in lieu of FDA-approved polidocanol, but such promotional statements are prohibited if they are false or misleading, such as baseless statements that compounded products are superior or failing to disclose significant risks associated with unapproved uses that are promoted.

There are numerous cases of injury resulting from various improperly compounded medications.11 An outbreak of meningitis in 2012 caused by a contaminated steroid injection intended for epidural injection made in a compounding pharmacy23 affected 753 patients in 20 states with 64 deaths.24 Subsequently, the United States Congress passed the Drug Quality and Security Act in November, 2013.25 Among other requirements, the Act stipulates that pharmaceutical compounders are not allowed to essentially copy products that are already FDA-approved and commercially available, unless there is a manufacturing product shortage.25 Serious patient illness and death associated with poor quality compounded drugs continue to occur.26 This is also made clear under Section 503A of the Federal Food, Drug, and Cosmetic Act:27
“The restrictions on making drugs that are essentially copies ensure that pharmacists and physicians do not compound drug products under the exemptions for patients who could use a commercially available drug product. Such a practice would create significant public health risks because patients would be unnecessarily exposed to drug products that have not been shown to be safe and effective and that may have been prepared under substandard manufacturing conditions. FDA has investigated serious adverse events in patients who received contaminated compounded drugs when a comparable approved drug, made in a facility subject to CGMP requirements, was available.”
Since compounded drugs have not undergone FDA review to determine their safety and effectiveness, their potency and purity cannot be assured as demonstrated by the current analysis of several compounded polidocanol products. It has been recognized for many years that physicians who use these products may be at risk legally in the event of an adverse outcome.28 A physician involved in litigation related to the use of a compounded sclerosant should be prepared to explain why an unapproved agent was used when an FDA-approved agent is available and whether a compounded product was used to increase profit.29


Compounded drug products have not undergone FDA review to establish safety and efficacy. An analysis of seven samples of compounded polidocanol injection found all of them to be outside the labeled concentration and five had excessive contaminant levels. Physicians who use these products should consider FDA-approved products to ensure optimal treatment outcomes.29


The authors acknowledge the editorial assistance of Dr. Carl S. Hornfeldt, Apothekon, Inc., during the preparation of this manuscript. This work was funded by Merz North America, Raleigh, NC.


The authors have no further disclosures to report.


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Margaret Mann MD