Ophthalmic Timolol Causes Systemic Exposure

By Reuters Staff

March 05, 2019

NEW YORK (Reuters Health) - Most children given topical timolol to treat hemangioma have plasma levels of the drug that would have beta-blocking effects in adults, new findings show.

"Off-label ophthalmic timolol has been rapidly adopted for treatment of infantile hemangioma since topical application of beta-blockers was presumed to have an improved safety profile compared to oral administration," Dr. Beth A. Drolet of the Medical College of Wisconsin in Milwaukee and colleagues write in the Journal of the American Academy of Dermatology, online February 18.

The team looked at 76 children with a median age of 6.7 months, most of whom received one drop of timolol a day. Among 92 samples provided, 93% had detectable levels of timolol.

Eighty percent had levels above 0.2 ng/mL, which in adults results in "measurable systemic beta-blocking activity," the authors note.

Hemangioma thickness was the only predictor of plasma concentration. "All three extreme outliers identified in our population were >6 months old and had very thick hemangiomas; paradoxically, these families had declined oral propranolol because of perceived increased systemic drug exposure and adverse event risk," Dr. Drolet and her team note.

They note, however, that "Although topical timolol results in systemic drug exposure, similar to oral beta-blockers, it appears to be well-tolerated with retrospective reviews and a meta-analysis reporting few adverse events in infants receiving 1-2 drops per day."

A phase 2 trial of timolol for hemangiomas now underway will provide clearer information about dose response and safety, the researchers add.

"Until then, our data, alongside previous publications, has clinical relevance; topical timolol can treat small, thin, hemangiomas. We recommend not exceeding 2 timolol drops 0.5% per day - the dose for which safety data have been reported," they write. "Oral beta-blockers should be considered for treatment of thick hemangiomas, since studies have shown topical timolol is less effective, and we have demonstrated greater systemic exposure."

They add: "Children may be most susceptible to adverse events from beta-blockers when a necessary stress response is inhibited (fasting, illness). Consequently, treating providers should consider discontinuing both topical and oral beta-blockers with severe illness, bronchospasm, or decreased oral intake."

Dr. Drolet was not available for an interview by press time.

SOURCE: https://bit.ly/2EERx0F

J Am Acad Dermatol 2019.