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Toxicity of topical timolol for infantile hemangiomas in preterm infants: Size matters

DII small banner By Warren R. Heymann, MD
Aug. 13, 2016

I have been using topical timolol (0.5% gel) for the past few years for infants with infantile hemangiomas (IH) with reasonable success, but I am always nervous about prescribing it, as data on the degree of topical absorption remains to be defined. I agree with McMahon et al who are “cautiously optimistic” about the use of topical timolol for IH, and use it under advisement. They appropriately warn of increased absorption of timolol on or near mucosal surfaces, on thinner skin sites such as the perineum, or on ulcerated lesions. They recommend considering monitoring for bradycardia and advise using an exact number of drops (no more than 1 or 2 per application). Clinicians and parents should recognize potential signs of systemic absorption, notably irritability, lethargy, poor feeding, mottling, and hypothermia (1).

Frommelt et al retrospectively reviewed the charts of 22 infants who received a Holter monitor to assess for an association between timolol administration and the risk of significant bradycardia. Four infants had episodic bradycardia detected by Holter monitoring. Two of these infants were full term and weighed > 3,000 g; their bradycardia was brief, rare, and unrelated to the timing of timolol application. The other two babies weighed < 2,500 g at the initiation of therapy; they had symptomatic bradycardia. Until such time that appropriate pharmacokinetic studies on the percutaneous absorption of topical timolol are performed, the authors make the following recommendations: 1) the dose should be kept to < 0.25 mg/kg/day; 2) if this is not possible, oral propranolol may be indicated; 3) Holter monitoring for bradycardia (< 80 beats per minute) should be considered for premature infants when initiating therapy before reaching a postmenstrual age of 44 weeks if results are readily available, as this may be a marker for potential adverse effects.
As in any therapy, it is easy to become complacent with experience. At his point, however, we are still on the learning curve on how to administer topical timolol properly for IH. Studies such as this remind us that we need to be vigilant and circumspect for our youngest, most vulnerable patients. Size matters when it comes to topical absorption and risk of toxicity. The smaller the patient, the greater our concern should be.

1. McMahon P, et al. Topical timolol for infantile hemangiomas: putting a note of caution in “cautiously optimistic”. Pediatr Dermatol 2012; 29: 127-30.
2. Frommelt P, et al. Adverse events in young and preterm infants receiving topical timolol for infantile hemangioma. Pediatr Dermatol 2016; 33: 405-14.

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