Safety of Propranolol Therapy for Severe Infantile Hemangioma
Prey S, Voisard J, Delarue A, et al
Prey and colleagues report the outcomes of a cohort of 906 children with infantile hemangioma (IH) who were referred to one of eight referral centers in France from 2010 to 2013 and treated with propranolol. All children had proliferative IH that was severe enough to require systemic therapy. This report focuses specifically on adverse drug reactions (ADRs) in children followed at monthly visits through age 24 months. The median dose of propranolol was 2 mg/kg/day. The median duration of therapy was 198 days, and the median duration of follow-up was 396 days.
Among children who had stopped therapy by the end of the study period, 83.7% had done so because of a satisfactory clinical outcome, whereas 5.8% stopped therapy after experiencing an ADR. Overall, 8.8% of children experienced at least one ADR, 2.6% of which were serious. The most common ADRs were respiratory disorders (primarily infections), which were reported in 31 children; six of these were deemed serious and related to propranolol. Sleep disturbances (primarily nightmares) occurred in 24.7% of the children, but only about one third of these were judged to be related to the propranolol. Vascular and digestive ADRs each occurred in 11.1% of children, although only two thirds of the vascular ADRs and one third of the digestive ADRs were related to taking propranolol. Four children (4.9%) experienced metabolic ADRs (hypoglycemia), all of which were believed to be caused by propranolol. All four children improved with discontinuation of drug.
Another four children (4.9%) experienced cardiac ADRs, half of which were blamed on propranolol. Two serious cardiac ADRs involved bradycardia, which occurred in children with severe comorbidities. One death occurred as a result of atrioventricular block after sclerosis of esophageal varices in a patient with biliary atresia and portal hypertension. The other serious episode of bradycardia resolved with discontinuation of the medication.
Propranolol was stopped at some point in 45 of 88 children (51%) due to concern about ADRs, but 40% of those children were able to restart therapy successfully. The investigators concluded that propranolol can be safely used to treat clinically severe IH, but patients require ongoing monitoring for ADRs. They suggest that parents should be counseled at each visit to discontinue propranolol during times of illness, particularly gastrointestinal illnesses, when intake may be compromised, and during respiratory illnesses when bronchospasm might be an issue.
Despite the fact that this is a single case series from one country, getting these clinical data out to practitioners is critically important. More and more children are treated for IH with propranolol, but individual pediatric providers will not have a great deal of experience with the drug. The important take-home message here is to become familiar with how the side effects manifest in infants, primarily the risks for hypoglycemia, bradycardia, and bronchospasm. I agree with the authors that parental education is also critically important. Another excellent resource for practitioners is a 2013 consensus report in Pediatrics on initiation and maintenance of propranolol for IH. That article reviewed data from 85 different studies with slightly more than 1100 participants, so the current report increases the number of patients with published outcomes by 82%! The consensus statement has good rules of thumb for exclusion from propranolol therapy as well as advice for monitoring. It's worth taking a look.
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Cite this: Treating Infantile Hemangioma: Adverse Drug Events With Propranolol - Medscape - Apr 06, 2016.