Efficacy of topical brimonidine-timolol for haemangioma of infancy and perils of off-label prescribing

We report three patients with superficial haemangiomas treated topically with Combigan ophthalmic solution (brimonidine 0.2%-timolol 0.5%), a combination selective α-2-adrenergic agonist and non-selective β-blocker Food and Drug Administration-approved for use in glaucoma. Topical brimonidine 0.2%-timolol 0.5% therapy improved the appearance of haemangiomas in all the cases. Two patients did not experience any adverse effects. One patient had hypothermic episodes which were initially thought to be because of brimonidine 0.2%-timolol 0.5% therapy. However, an episode occurred a few weeks after discontinuation and brimonidine 0.2%-timolol 0.5% therapy was ruled out as a cause. Despite the benefit, off-label use of brimonidine 0.2%-timolol 0.5% therapy served as a pitfall in the evaluation of an unusual constellation of worrisome symptoms. In conclusion, brimonidine 0.2%-timolol 0.5% therapy is a promising alternative in the topical treatment of haemangiomas. It may have synergistic effects and increased efficacy by targeting haemangiomas via two mechanisms (α-agonism and β-inhibition), but the risk of unforeseen adverse effects must always be considered when prescribing off-label treatment, especially in infants.