Oral Propranolol For Infantile Hemangiomas Research Articles

Early initiation of treatment with oral propranolol for infantile hemangioma improves success rate.

Early referral and treatment of infantile hemangioma (IH) is a major challenge for treatment success. However, there is a lack of data supporting a specific threshold for initiating treatment with oral propranolol. The aim of this analysis was to find factors, such as age at treatment initiation, leading to a higher success rate with oral propranolol treatment. Based on data from the pivotal phase 2-3 clinical trial of oral propranolol in IH, we used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify sub-groups presenting a high probability of occurrence of the predefined outcome (i.e., success [complete or nearly complete resolution of the target hemangioma] at 6months of treatment). Our analyses identified that patients who started oral propranolol 3mg/kg/day before the age of 10 weeks had a success rate of 86%, higher than the 60% success rate for all patients that received the same regimen commencing after 10 weeks of age. Treatment initiation before 10 weeks of age was associated with a significantly higher rate of treatment success with oral propranolol 3mg/kg/day. Infants with IH requiring treatment should be referred to an expert center and treated as soon as possible.

The future of surgical technique publication at JCRS and JCRO.

The future of surgical technique publication at JCRS and JCRO.

The effectiveness of oral propranolol for infantile hemangioma on the head and neck region: A case series

IntroductionInfantile hemangioma is the most common tumor in infancy, with 60% occurring on the face and neck. A large tumor involving the facial region will cause significant aesthetic and functional impairment and isn't always easy to treat surgically. A non-invasive treatment is needed for this condition. Propranolol has recently been used as a choice of treatment in infantile hemangioma. Presentation of caseWe presented two cases of large problematic infantile hemangioma that were successfully managed with oral propranolol. DiscussionLarge problematic lesions that ulcerate and bleed often need surgery; however, a substantial defect resulting from surgery is tricky to reconstruct and can cause significant scar. Propranolol is used because of its efficacy and low risk characteristics. ConclusionPropranolol is an effective treatment to reduce the need of surgical intervention in problematic hemangioma.

Risks With Use of Oral Propranolol for Infantile Hemangioma

Risks With Use of Oral Propranolol for Infantile Hemangioma

Safety of Oral Propranolol for Infantile Hemangioma.

The safety of oral propranolol for infantile hemangioma has not yet been studied at population level since the pediatric use marketing authorization was obtained in Europe. A survey of a nationwide, claim-based observational cohort of children <3 years old, with at least 1 delivery of oral propranolol between July 2014 and June 2016, was performed by using the database of the French National Health Insurance system. Standardized morbidity ratios (SMRs) were calculated by using, from the same database, a representative random sample of nonexposed subjects. The main outcomes were hospitalizations for cardiovascular (conduction disorders, bradycardia, and hypotension), respiratory (bronchial hyperactivity and bronchospasm), or metabolic events (hypoglycemia and hyperkalaemia), identified through the hospitalization diagnostic codes of the International Classification of Diseases, 10th Revision. The main analysis was conducted separately on "healthy" children (N = 1484), that is, free from of any prespecified underlying disease and on children with 1 of these underlying diseases (N = 269). In all, 1753 patients <3 years of age had at least 2 deliveries of oral propranolol. In the healthy population, we observed 2 cardiovascular events (SMR = 2.8 [0-6.7]), 51 respiratory events (SMR = 1.7 [1.2-2.1]), and 3 metabolic events (SMR = 5.1 [0-10.9]). In the population with an underlying disease (mainly congenital heart disease), we observed 11 cardiovascular events leading to an SMR of 6.0 (2.5-9.6). SMRs were not significantly raised for respiratory or metabolic events in this "nonhealthy" population. In this study on a large continuous nationwide claims database, we confirm the safety profile of oral propranolol in healthy children to be good.

Study of Cognitive Function in Children Treated with Propranolol for Infantile Hemangioma

Oral propranolol is considered the first choice for the treatment of infantile hemangiomas (IHs). There is a concern that administering propranolol in newborns and infants could induce adverse effects in learning and memory processes in the long term. The purpose of this study was to assess cognitive and memory functions in children who had been treated with propranolol for IH during their infancy. A total of 23 children between 5 and 7.5years of age who had been treated with oral propranolol for IH during infancy were tested for cognitive functions with the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) test and for memory functions with the Test of Memory and Learning (TOMAL). Comparison of our sample with a normal distribution by a Shapiro-Wilk W test showed no significant difference for any of the composite scores in the WPPSI-IV and TOMAL tests except for positive asymmetry and concentration of scores around average (p = 0.01) in the WPPSI-IV composite score (mean intelligence), due to one atypically high score. The distribution of scores for intelligence and memory scales in our study population was similar to that in the reference general population. These results fail to support any significant disturbance in intelligence and memory development in children treated during infancy with propranolol for IH.

Efficacy and safety of oral propranolol for infantile hemangioma in Japan

There have been few reports on the efficacy and safety of oral propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients. A multicenter, open-label phase III study was conducted to evaluate the efficacy and safety of oral propranolol solution in Japanese infants aged 35-150 days with proliferating IH. Thirty-two patients were enrolled in the study, received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the study. The success rate (complete or nearly complete resolution) at week 24 (primary endpoint) was 78% (95%CI: 60-91%). The improvement rate since the previous visit was 100% (32/32) after week 5. Overall, the IH surface area, maximum diameter, and color intensity all decreased over time. Consistency in assessment between the centralized and the investigator on-site assessments was observed in 26 patients. Of the 32 patients, 11 needed further treatment other than the study drug. The incidence of adverse events (AE) and drug-related AE was 97% and 31%, respectively. AE that occurred in ≥two patients were either typical of propranolol use (such as blood pressure decrease) or common events in infants. AE that resulted in dose reduction were observed in two patients, but no serious AE or AE that led to study drug discontinuation were observed. Oral propranolol solution at 3 mg/kg/day is effective and safe in Japanese IH patients.

Safety and effectiveness of oral propranolol for infantile hemangiomas started before 5\xa0weeks and after 5\xa0months of age: an Italian multicenter experience

BackgroundDespite not being licensed for the treatment of infantile hemangiomas (IH) in infants younger than 5 weeks or older than 5 months, propranolol is often used in these age groups to prevent or to treat potentially severe complications. The objective of the present study was to review the experience of 8 Italian pediatric and dermatologic centers regarding propranolol treatment for IH started before 5 weeks or after 5 months of age.MethodsWe retrospectively reviewed the records of patients followed up for IH, on propranolol treatment started before 5 weeks or after 5 months of age, and collected information on sociodemographic data, treatment indications, IH involution, IH relapse, and treatment side effects.ResultsA total of 343 patients were enrolled; 15 were started on propranolol before 5 weeks (group 1), 328 were started after 5 months of age (group 2). The most frequent indications were permanent aesthetical disfigurement (91.8%) and function threatening complications (42.6%).In most cases, the treatment was effective. The involution was partial in 67.7% of patients. In 11.8% of cases a relapse was observed. No relapse was observed in group 1. Treatment complications were reported in 15.8% of children, most frequently sleep disorders (6.6%), followed by irritability (5.1%) and diarrhea (2.2%). Only a case of mild constipation was observed in group 1.ConclusionThe safety and effectiveness profile of propranolol in infants younger than 5 weeks or older than 5 months may be acceptable. Taking in account propranolol's potential in preventing severe complications, further studies should assess the acceptability of propranolol treatment, especially in the <5-week age group .

Oral propranolol for infantile hemangiomas: a prospective study on the role of 48-hour Holter monitoring in additional safety assessment

Purpose: Oral propranolol has been recently approved for infantile hemangiomas (IHs), but potential side effects stay a challenge. We sought to make an additional assessment on oral propranolol safety for this indication.Materials and methods: Prospective study included 108 infants consecutively treated for IHs at the University Children’s Hospital Tirsova, Belgrade from January 2010 to December 2013. Propranolol was administered orally at a daily dose of 0.5 mg/kg and doubled every 48 hours in the absence of side effects until reaching the maximum dose of 2 mg/kg daily. Systolic and diastolic blood pressure and heart rate were measured every 48 hours with clinical observation. Heart rate was monitored by standard electrocardiogram (ECG) and 48-hour Holter ECG.Results: Statistically significant, but asymptomatic decreases in systolic blood pressure and heart rate recorded by Holter ECG were observed during the first doubling of dose and then remained stable. Arrhythmias were not detected. Despite mild sleep disturbance observed in 31% of infants in the hospital milieu, Holter monitoring indicated circadian rhythm maintenance.Conclusions: Oral propranolol for IHs does not remarkably affect heart rhythm including circadian variations throughout hospital initiation. Therefore, there is no necessity for Holter monitoring in additional safety assessment.

Safety of Oral Propranolol for the Treatment of Infantile Hemangioma: A Systematic Review.

Given the widespread use of propranolol in infantile hemangioma (IH) it was considered essential to perform a systematic review of its safety. The objectives of this review were to evaluate the safety profile of oral propranolol in the treatment of IH. We searched Embase and Medline databases (2007-July 2014) and unpublished data from the manufacturer of Hemangiol/Hemangeol (marketed pediatric formulation of oral propranolol; Pierre Fabre Dermatologie, Lavaur, France). Selected studies included ≥10 patients treated with oral propranolol for IH and that either reported ≥1 adverse event or effect (AE) or planned to capture AEs. Data capture was standardized and extracted study design, demographic characteristics, IH characteristics, intervention, and safety outcomes. AEs were assigned a system organ class and preferred term. A total of 83 of 398 identified literature records met the inclusion criteria, covering 3766 propranolol-treated patients. The manufacturer's data for 3 pooled clinical trials (435 propranolol-treated patients) and 1 Compassionate Use Program (1661 patients) were included. AE data were reported for 1945 of 5862 propranolol-treated patients. The most frequently reported AEs included a range of sleep disturbances, peripheral coldness, and agitation. The most serious AEs (atrioventricular block, bradycardia, hypotension, bronchospasm/bronchial hyperreactivity, and hypoglycemia-related seizures) were managed by decreasing doses or temporary/permanent discontinuation of propranolol. Limitations included the variety of included study designs; monitoring, collection, and reporting of AE data; small sample sizes for some articles; and the wide scope of review. Oral propranolol is well tolerated if appropriate pretreatment assessments and within-treatment monitoring are performed to exclude patients with contraindications and to minimize serious side effects during treatment.

Scoring the therapeutic effects of oral propranolol for infantile hemangioma: A prospective study comparing the Hemangioma Activity Score (HAS) with the Hemangioma Severity Scale (HSS)

Validated and reliable instruments to measure disease severity are needed to substantiate the benefit of therapies for infantile hemangioma. Two purpose-made systems have been described: the Hemangioma Activity Score (HAS) and the Hemangioma Severity Scale (HSS). We sought to compare the HAS with the HSS in terms of ease of use, accuracy, and outcome in infants treated with oral propranolol. A prospective study of 54 infants with infantile hemangioma was conducted from October 2009 to December 2012. Propranolol was initiated at 0.5 mg/kg/d and increased to 2 mg/kg/d on day 3. The HAS and the HSS were applied independently by 2 observers. Intraclass correlation coefficients of the HAS and HSS between the observers was comparable but HSS scores often remained the same upon improvement of the infantile hemangioma and therefore did not reflect disease severity. HAS decreased over time, with a dramatic drop in the first week reflecting an immediate therapeutic response. This is a single-institution study and there may have been some selection bias in the patients who were referred for treatment. This study suggests that the HAS is preferable to the HSS in evaluating infantile hemangioma response to treatment.

A Randomized, Controlled Trial of Oral Propranolol for Infantile Hemangioma

Infantile hemangiomas (IH) affect up to 10% of infants. A rapid proliferative phase is followed by slow spontaneous involution. Approximately 12% of IH

Propranolol for infantile hemangiomas: Our preliminary experience

Objective: Propranolol has recently been introduced as a novel pharmacologic treatment for infantile hemangiomas. This study explores the impact of propranolol on infantile hemangiomas. Study Design : Prospective study Materials and Methods: Propranolol was given to 38 children (21 girls and 17 boys) propranolol was administered with a dose of 2mg/kg per day, given in 2 or 3 divided doses. Children between age 3 weeks to 12 weeks included in study. Oral propranolol given between February 2013 to January 2014. Serial photographs taken at 6-8 weeks interval during the course of their therapy to record clinical response. Results: thirty eight children with complete photo documentation were treated with oral propranolol for infantile hemangiomas between February 2013 to January 2014.Out of 38 patient 36 patients showed improvement in their hemangiomas by effects on color and rapid/progressive reduction in size during propranolol therapy. Lesions were determined as complete resolution (n -3, 7.5%), ongoing resolution (n -33, 86.8%), or no sign of resolution ie no response (n - 2, 5%). No serious side effects of propanolol were observed in any patients. Conclusion: Propranolol may revolutionize the treatment of hemangiomas . At therapeutic doses (2mg/kg/day) , propranolol is safe and effective in the treatment of infantile haemangiomas.

Propranolol in the Treatment of Problematic Infantile Hemangioma: Review of 35 Consecutive Patients from a Vascular Anomalies Clinic

Propranolol, a nonselective β-blocker, has been reported as efficient for controlling the growth of complicated infantile hemangiomas (IHs). No uniformly accepted protocol exists regarding the administration of oral propranolol for IH. We sought to share our experience using propranolol for problematic IH and to evaluate the efficacy of this treatment modality. A retrospective chart review analysis was performed for 35 consecutive children treated with propranolol as an oral solution on an outpatient basis in our dermatology/vascular anomalies clinic. A protocol was established with the help of our pediatric cardiologists, including pretreatment electrocardiography and echocardiography. Medical photographs taken after 2 months of treatment were rated by two independent evaluators. We treated 31 girls and 4 boys with a median age of 3.5 months. Rapid improvement was reported in the first days of treatment in 34 patients. Mean improvement after 2 months was 61.5%. No serious adverse effects were reported. Propranolol was effective in controlling the proliferative phase of problematic IH. It was well tolerated in our study. Outpatient treatment is possible if parents follow strict guidelines. Propranolol should be a first-line treatment for problematic IH in carefully selected patients.

Oral Propranolol for Infantile Hemangioma: The New Treatment of Choice?

Infantile hemangiomas are vascular tumors that affect about 5% of infants. Although most lesions will spontaneously involute, some lesions can create life-threatening or functional complications because of their location. In a randomized placebo-controlled trial, researchers evaluated the efficacy and safety of oral propranolol (titrated to a maximum dose of 2 mg/kg divided in 3 doses …

Propranolol for infantile hemangiomas: Early experience at a tertiary vascular anomalies center

Propranolol has recently been introduced as a novel pharmacologic treatment for infantile hemangiomas. Systematic examination of this treatment in a tertiary care setting has not been described. This study explores the impact of propranolol on both proliferative and involuting hemangiomas at a tertiary vascular anomalies center. Retrospective single institution review. We reviewed children treated with propranolol for problematic hemangiomas followed by a blinded prospective analysis of serial photographs taken during the course of their therapy. Parental questionnaires were obtained to evaluate perceived therapeutic response and complications to oral propranolol. Thirty-two children with complete photo documentation were treated with oral propranolol for infantile hemangiomas between September 2008 and June 2009. Twenty-seven patients began therapy during the proliferative phase of their lesions (mean age, 4.9 months), whereas five patients began during the involutional phase (mean age, 19.4 months). Ninety-seven percent of patients displayed improvement in the quality of their hemangiomas during propranolol therapy. Patients were determined to be excellent responders (n = 16, 50%), partial responders (n = 15, 47%), or nonresponders (n = 1, 3%). Partial and nonresponders received adjuvant therapy (75%, laser therapy; 31%, steroid injections). Ten patients experienced minor but reportable side effects to propranolol, including somnolence (27.2%), gastroesophageal reflux (9.1%), respiratory syncytial virus exacerbation (4.5%), and rash (4.5%). Propranolol may revolutionize the treatment of problematic hemangiomas that cause imminent functional or cosmetic sequelae. At therapeutic doses, propranolol is safe and effective in the majority of patients. Adjunctive therapies may still be required. Minor side effects, expected from beta-blocker therapy, are common but easily managed.