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We searched Embase and Medline databases (2007-July 2014) and unpublished data from the manufacturer of Hemangiol/Hemangeol (marketed pediatric formulation of oral propranolol; Pierre Fabre Dermatologie, Lavaur, France).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.
Unité de Dermatologie Pédiatrique et Centre d'Investigation Clinque Pédiatrique 1401, Hôpital Pellegrin-Enfants, Bordeaux, France; christine.labreze@chu-bordeaux.fr.
Christine
C
Léaute-Labrèze
Service de Dermatologie, Hôpital Necker Enfants Malades, Paris, France.
Olivia
O
Boccara
Service Explorations Cardiovasculaires et de Cardiologie Pédiatrique, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
Caroline
C
Degrugillier-Chopinet
Service de Dermatologie et Centre de Référence des Maladies Rares de la Peau, Hôpital Larrey, Toulouse, France.
Juliette
J
Mazereeuw-Hautier
Unité de Dermatologie Pédiatrique et Centre d'Investigation Clinque Pédiatrique 1401, Hôpital Pellegrin-Enfants, Bordeaux, France.
Sorilla
S
Prey
Pierre Fabre Medicament, Boulogne, France.
Geneviève
G
Lebbé
Institut de Recherche Pierre Fabre, Toulouse, France; and.
Stéphanie
S
Gautier
Pierre Fabre Dermatologie, Lavaur, France.
Valérie
V
Ortis
Institut de Recherche Pierre Fabre, Toulouse, France; and.
Martine
M
Lafon
Institut de Recherche Pierre Fabre, Toulouse, France; and.
Agnès
A
Montagne
Pierre Fabre Dermatologie, Lavaur, France.
Alain
A
Delarue
Pierre Fabre Dermatologie, Lavaur, France.
Jean-Jacques
JJ
Voisard
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006391:Hemangioma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011433:Propranolol / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D011433:Propranolol