Retrospective Analysis Of Off-Label Treatment With Beta-Blockers In Pediatric Patients With Hemangiomas Diagnosed Between January And December 2009 At Hospital Infantil Albert Sabin.
Creators: name: Felix, Francisco
Publisher: name: Zenodo
Year: 2016
Subjects: propranolol, beta-blocker, hemangioma

description: Hemangiomas are the most common benign tumors of childhood, with mostly evolving to spontaneous remission. More rarely, one or more hemangiomas of greater proportions or located in vital organs can cause serious health problems, and potentially result in death of pediatric patients. In these cases, the conventional therapy, while grounded only in limited uncontrolled trials involves the use of high doses of corticosteroids, vincristine or interferon alpha 2a. The effectiveness of these treatment regimens is variable, although the literature show a response rate of 90%. However, in a considerable number of cases, residual lesions remain and, although they are not life threatening, bring discomfort and aesthetic problems for patients throughout their lives. Patients with these residual lesions depend on plastic surgical treatment in the future, with aesthetically variable results.

Recently, the publication of a report of 11 cases opened new perspective of treatment for patients with infantile hemangiomas. French researchers casually discovered a quick and highly effective effect of propranolol in doses usually recommended in pediatrics, in patients with infantile hemangiomas refractory to conventional therapy. The mechanism of action is still discussed, and may involve the participation of the signaling pathways of cyclic adenosine monophosphate (cAMP), modulation, of vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF-1a). Several authors have published case reports showing successful treatment with propranolol in pediatric patients with hemangiomas. Based on these reports and the fact that propranolol is widely used in adults and, less often, also in children, with an excellent safety profile and minimal side effects, we decided to use this drug in selected patients. Patients to whom we indicate the use had already made conventional treatment and had large residual lesions that caused significant discomfort or aesthetic damage and had no more indication of new conventional treatment because of the risk of side effects. We offered the new treatment to the legal representatives of patients, obtaining written informed consent thereof (annex 1).

Treatment was offered as "off-label". Off-label treatment is the use of a known safe medication in humans, approved by ANVISA (Brazillian drug regulatory agency) or other regulatory agency to treat certain diseases, in order to treat other diseases that initially were not predicted by the approval. This use is the responsibility of the prescribing physician, which should explain the legal representative of a patient this condition of "off-label" treatment. We did notify the Commission of Pharmacy and Therapeutics at Children's Hospital Albert Sabin informing the non-standard use of propranolol in these patients.

Subsequently, in view of the good results achieved in the short term, we offered treatment to the legal representatives of patients with newly diagnosed infantile hemangiomas, in conjunction with conventional treatment as indicated. One of the children used metoprolol, cardioselective beta-blocker with cardiovascular effect similar to propranolol, due to inability to receive drugs by oral route in the initial phase of treatment. Propranolol is a drug with wide clinical experience and reduced potential for adverse effects in contrast with the conventional forms of treatment listed. This indicates that potentially it will replace other forms of conventional therapy as first choice for treatment of childhood hemangiomas in the near future.
description: Project proposal that was submitted to the Institutional Review Board of Hospital Infantil Albert Sabin and approved in 11/18/2009. Number of approval CAAE 39834614.6.0000.5042
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