What is the role of propranolol in the treatment of infantile hemangiomas?

Updated: Feb 06, 2019
  • Author: Richard J Antaya, MD; Chief Editor: William D James, MD  more...
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Answer

Propranolol oral solution (Hemangeol) was approved by the FDA in March 2014. Approval was based on the results from a dose-ranging study of 460 infants aged 35 days to 5 months with proliferating hemangiomas (excluding life-threatening, ulcerated, or function-threatening infantile hemangiomas). Overall, 2 (4%) of 55 patients in the placebo arm and 61 (60%) of 101 patients taking propranolol 3.4 mg/kg/day for 6 months had complete or nearly complete resolution of their hemangioma at week 24 (P<.0001).<ref>69</ref> [79] Beta-blockers, most specifically propranolol and more recently topical timolol, have been in use since mid 2008 for infants with severe or disfiguring hemangiomas. [80, 81] Several reports in the literature describe efficacy for life- and sight-threatening airway and retro-orbital hemangiomas, respectively. [65, 82, 83] Some have been treated with the beta-1 selective blockers acebutolol and atenolol. However, most infants reported have been treated with the nonselective beta-blocker, propranolol, at a dose of 2-3mg/kg/day in 2-3 divided doses. Duration of therapy varies from 2-12 months. As early as 24 hours after the initiation of therapy, many infantile hemangiomas have begun to change from intense red to purple, with evidence of softening. Most continue to improve until nearly flat and with significantly diminished color.

Treatment of nasal infantile hemangioma with propranolol reduced the need for invasive treatment in a retrospective cohort study of 58 children (mean age, 5 months). [84, 85] The researchers divided the study participants into a prepropranolol group, a propranolol group, and a nonpropranolol group. Infants treated with propranolol for a mean of 7.6 months at a total dosage of 2 mg/kg/day were 56% less likely than infants in the prepropranolol group to undergo any invasive treatment, 61% less likely to undergo surgical treatment, and 25% less likely to receive laser treatment.

The mechanism of action of propranolol in these patients is unknown; however, some hypothesize that local vasoconstriction may be a factor, which is based on the early color change and softening of the lesion. One study has demonstrated that nonspecific and beta 2-selective blockers (eg, propranolol) triggered apoptosis of capillary endothelial cells in adult rat lung tissue, suggesting a similar mechanism may be plausible for hemangioma endothelial cells. [86] Propranolol has also been shown to inhibit signaling from the renin-angiotensin system. See Causes.

One published consensus protocol from 2013 describes initiating propranolol therapy in infants with hemangiomas. [11] Therapy should be approached with extreme caution in neonates and infants who generally do not have preexisting venous hypertension or any other hemodynamic disorder. Of particular note, infants with hemangiomas associated with PHACE syndrome with cerebrovascular anomalies are at higher risk for cerebral vascular accidents and therefore should not receive beta-blockers unless the benefits outweigh the risks.

Provisional guidelines for initiation of treatment are described below.


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