Off-Label Use and Safety of Drug Use in Vascular Anomalies

Abstract

<b><i>Background:</i></b> Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA). <b><i>Objectives:</i></b> The aim of this work was to quantify off-label drug use in VA and assess its safety. <b><i>Methods:</i></b> A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. <b><i>Results:</i></b> We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs. <b><i>Conclusions:</i></b> Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.

Defining vascular anomaly phenotypes in children based on a systematic literature search: A critical step in developing a single severity score for interventional clinical trials

“…9 Sirolimus has been prescribed when the perceived clinical severity of the VA outweighs the potential drug-related adverse events. 8 As such, treatment with sirolimus can therefore be used as a surrogate measure of severity. VA severity was defined by reviewing phenotypes of all VA, prompting systemic administration of sirolimus.…”

“…6 However, only a subset of patients display clinical consequences associated with significant medical, social, and economic burden, 7 prompting surgical, interventional radiology and medical treatment. 8 Despite the prevalence of these conditions, the improved understanding of their pathophysiology and/or genetic background, and increased awareness within healthcare workers, no validated pharmacodynamic criteria exist to assess drug efficacy. The absence of a validated severity scoring system limits comparison between cohorts, translation of research results into clinical practice, and favors a nonevidence-based practice influenced by local practice.…”

“…This precludes evidence-based practices as reflected by the low level of evidence surrounding medical therapies in this field. 8,14 In systemic treatments (e.g., sirolimus), the absence of a previously validated scoring system is circumvented by combining different treatment response data: generic quality-of-life scores, as well as treatment-response assessment using oncology-based radiologic and clinical response scoring systems. [15][16][17] Of note, none of these scores or their combination has ever been validated in patients with VA, creating an unmet need for a VA-specific score to be generated and subsequently vali-dated.…”

“…VA affect 1.5% of the general population 6 . However, only a subset of patients display clinical consequences associated with significant medical, social, and economic burden, 7 prompting surgical, interventional radiology and medical treatment 8 …”

“…Nevertheless, for the most severe and complex VAs requiring specialized multidisciplinary care, no severity scores exist. This precludes evidence‐based practices as reflected by the low level of evidence surrounding medical therapies in this field 8,14 . In systemic treatments (e.g., sirolimus), the absence of a previously validated scoring system is circumvented by combining different treatment response data: generic quality‐of‐life scores, as well as treatment‐response assessment using oncology‐based radiologic and clinical response scoring systems 15–17 .…”