Topical timolol maleate for treatment of infantile haemangiomas: preliminary results of a prospective study

Abstract

An infantile haemangioma (IH) is a benign tumour of infancy. The standard approach to uncomplicated lesions is 'wait and see', but active intervention is sometimes preferred to avoid the unpredictable risk of cosmetic disfigurement. Topical beta-blockers were recently introduced as an effective alternative in such cases, but data are still lacking. We report the initial phase of a prospective study evaluating the efficacy and safety of topical timolol gel for IH, and present the interim analysis of the first 25 patients who completed a 6-month course of treatment. These 25 patients, with 39 localized, superficial haemangiomas, were treated with timolol 0.1% gel for 6 months and evaluated at 4-week intervals using the Physician's Global Assessment Score; the mean change was an 85% improvement from baseline, and complete clearance was achieved in four children. The treatment was more effective for plaque than for nodular lesions, and for proliferating than for involuting lesions. No side-effects were seen or reported. These early data confirm that timolol is a very effective and relatively safe treatment for small, localized, superficial IHs.

Topical Timolol Solution Versus Laser in Treatment of Infantile Hemangioma: A Comparative Study

“…The effective penetration of timolol maleate is due to two factors: the immature skin barrier function of an infant younger than 1 year and the lipophilic property of the timolol maleate, which enhances skin penetration (11,12). Our results matched those of other studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) that used timolol solution for the treatment of superficial hemangiomas, but in mixed hemangioma lesions we observed clearance of the superficial part, whereas the deep part responded partially. Xue and Hildebrand (6) obtained excellent results when timolol solution was used to treat two cases of deep hemangiomas.…”

Topical Timolol Solution Versus Laser in Treatment of Infantile Hemangioma: A Comparative Study

“…The effective penetration of timolol maleate is due to two factors: the immature skin barrier function of an infant younger than 1 year and the lipophilic property of the timolol maleate, which enhances skin penetration (11,12). Our results matched those of other studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) that used timolol solution for the treatment of superficial hemangiomas, but in mixed hemangioma lesions we observed clearance of the superficial part, whereas the deep part responded partially. Xue and Hildebrand (6) obtained excellent results when timolol solution was used to treat two cases of deep hemangiomas.…”

RCT of Timolol Maleate Gel for Superficial Infantile Hemangiomas in 5- to 24-Week-Olds

“…Posttrial follow-up of the majority of study candidates, however, has provided the investigators with the impression that no significant rebound of IHs occurred in those successfully treated with topical timolol maleate gel once the medication ceased. This finding is supported in other studies in which no significant IH rebound at 4 weeks after 8 to 30 weeks of treatment, 21 at 4 months after 6 months of treatment, 20 and at 3 to 6 months after a mean treatment duration of 3.4 6 2.7 months 19 was described.…”

Fractional Carbon Dioxide Laser–Assisted Drug Delivery of Topical Timolol Solution for the Treatment of Deep Infantile Hemangioma: A Pilot Study

“…The pharmacokinetics of cutaneously applied timolol have not been studied in detail. Studies on the pharmacokinetics and beta-blocking effects of transdermal timolol patches (5% timolol, 0.2 mg/cm 2 ) found plasma concentration levels to be below the detection limit after application for 48 hours (12). In our study, plasma timolol concentration was also below the detected sensitivity limit (20 pg/mL).…”

Topical Timolol Solution Versus Laser in Treatment of Infantile Hemangioma: A Comparative Study

“…The effective penetration of timolol maleate is due to two factors: the immature skin barrier function of an infant younger than 1 year and the lipophilic property of the timolol maleate, which enhances skin penetration (11,12). Our results matched those of other studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) that used timolol solution for the treatment of superficial hemangiomas, but in mixed hemangioma lesions we observed clearance of the superficial part, whereas the deep part responded partially. Xue and Hildebrand (6) obtained excellent results when timolol solution was used to treat two cases of deep hemangiomas.…”

RCT of Timolol Maleate Gel for Superficial Infantile Hemangiomas in 5- to 24-Week-Olds

“…Posttrial follow-up of the majority of study candidates, however, has provided the investigators with the impression that no significant rebound of IHs occurred in those successfully treated with topical timolol maleate gel once the medication ceased. This finding is supported in other studies in which no significant IH rebound at 4 weeks after 8 to 30 weeks of treatment, 21 at 4 months after 6 months of treatment, 20 and at 3 to 6 months after a mean treatment duration of 3.4 6 2.7 months 19 was described.…”

Fractional Carbon Dioxide Laser–Assisted Drug Delivery of Topical Timolol Solution for the Treatment of Deep Infantile Hemangioma: A Pilot Study

“…The pharmacokinetics of cutaneously applied timolol have not been studied in detail. Studies on the pharmacokinetics and beta-blocking effects of transdermal timolol patches (5% timolol, 0.2 mg/cm 2 ) found plasma concentration levels to be below the detection limit after application for 48 hours (12). In our study, plasma timolol concentration was also below the detected sensitivity limit (20 pg/mL).…”

Topical Timolol Solution Versus Laser in Treatment of Infantile Hemangioma: A Comparative Study

“…The effective penetration of timolol maleate is due to two factors: the immature skin barrier function of an infant younger than 1 year and the lipophilic property of the timolol maleate, which enhances skin penetration (11,12). Our results matched those of other studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) that used timolol solution for the treatment of superficial hemangiomas, but in mixed hemangioma lesions we observed clearance of the superficial part, whereas the deep part responded partially. Xue and Hildebrand (6) obtained excellent results when timolol solution was used to treat two cases of deep hemangiomas.…”

RCT of Timolol Maleate Gel for Superficial Infantile Hemangiomas in 5- to 24-Week-Olds

“…Posttrial follow-up of the majority of study candidates, however, has provided the investigators with the impression that no significant rebound of IHs occurred in those successfully treated with topical timolol maleate gel once the medication ceased. This finding is supported in other studies in which no significant IH rebound at 4 weeks after 8 to 30 weeks of treatment, 21 at 4 months after 6 months of treatment, 20 and at 3 to 6 months after a mean treatment duration of 3.4 6 2.7 months 19 was described.…”

Fractional Carbon Dioxide Laser–Assisted Drug Delivery of Topical Timolol Solution for the Treatment of Deep Infantile Hemangioma: A Pilot Study

“…The pharmacokinetics of cutaneously applied timolol have not been studied in detail. Studies on the pharmacokinetics and beta-blocking effects of transdermal timolol patches (5% timolol, 0.2 mg/cm 2 ) found plasma concentration levels to be below the detection limit after application for 48 hours (12). In our study, plasma timolol concentration was also below the detected sensitivity limit (20 pg/mL).…”